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>>> Iovance Biotherapeutics, Inc. (IOVA), a clinical-stage biotechnology company, focuses on developing and commercializing cancer immunotherapy products to harness the power of a patient's immune system to eradicate cancer cells. The company's lead product candidate is lifileucel that is in Phase II clinical trial for the treatment of metastatic melanoma and cervical cancer. It also develops LN-145 for the treatment of metastatic non-small cell lung cancer; IOV-4001 for the treatment of melanoma non-small cell lung cancer; IOV-2001; and IOV-3001. Iovance Biotherapeutics, Inc. has collaborations and licensing agreements with H. Lee Moffitt Cancer Center; M.D. Anderson Cancer Center; Ohio State University; Centre hospitalier de l'Université de Montreal; Cellectis S.A.; Novartis Pharma AG; Melanoma Institute Australia; and Beth-Israel Deaconess Medical Center. The company was formerly known as Lion Biotechnologies, Inc. and changed its name to Iovance Biotherapeutics, Inc. in June 2017. Iovance Biotherapeutics, Inc. was incorporated in 2007 and is headquartered in San Carlos, California.
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>>> Acurx Pharmaceuticals, Inc. (NASDAQ:ACXP) Q3 2023 Earnings Call Transcript November 14, 2023
Insider Monkey
https://www.insidermonkey.com/blog/acurx-pharmaceuticals-inc-nasdaqacxp-q3-2023-earnings-call-transcript-1223844/#q-and-a-session
Acurx Pharmaceuticals, Inc. beats earnings expectations. Reported EPS is $-0.23952, expectations were $-0.28.
Operator: Ladies and gentlemen, good morning, and welcome to the Acurx Pharmaceuticals Third Quarter 2023 Earnings Conference Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Rob Shawah, Chief Financial Officer. Please go ahead.
Robert Shawah: Thank you, Ryan. Good morning, and welcome to our call. This morning, we issued a press release providing financial results and company highlights for the third quarter of 2023, which is available on our website at acurxpharma.com. Joining me today is Dave Luci, President and CEO of Acurx, who will give a corporate update and outlook; and Bob DeLuccia, our Executive Chairman, who will provide his perspective as the manager of our development programs, including the Phase II clinical trial. After Dave’s comments, I’ll provide some highlights of the financials for the quarter ended September 30, 2023, and then turn the call back over to Dave for his closing remarks. As a reminder, during today’s call, we’ll be making certain forward-looking statements.
A research laboratory arranged with a variety of test tubes filled with liquids for biopharmaceutical research.
These forward-looking statements are based on current information assumptions, estimates and projections about future events that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in forward-looking statements. Investors should consider these risks and other information described in our filings made with the Securities and Exchange Commission, including our quarterly report on Form 10-Q, which we filed yesterday, Monday, November 13, 2023. You are cautioned not to place undue reliance on these forward-looking statements and Acurx disclaims any obligation to update such statements at any time in the future. This conference call contains time-sensitive information that’s accurate only as of the date of this live broadcast today, November 14, 2023.
Acurx undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date and time of this conference call. I’ll now turn the call over to Dave Luci. Dave?
David Luci: Thanks, Rob. Good morning, everyone and thanks for joining us to review our financial results for the third quarter and also to cover some exciting recent updates. Then we’d be pleased to take any questions. On October 2, 2023, we ended enrollment in our Phase IIb clinical trial of ibezapolstat, our lead antibiotic candidate for the treatment of patients with C. difficile infection or CDI. On November 2, 2023, we reported top line data from the Phase II clinical trial, including the ibezapolstat clinical cure rate at end of treatment or EOT of 96%, 25 out of 26 patients, including 100% in Phase IIa 10 for 10 and 94% in Phase IIb 15 for 16, as well as the cure rate for oral vancomycin at EOT of a 100% 14 of 14. No safety concerns were reported in either arm of the Phase IIb clinical trial or in the Phase IIb open-label trial.
Based on the Phase II data, in consultation with our scientific advisors, we determined that clear evidence of clinical cure has been established with ibezapolstat, and it is clinically comparable to vancomycin. Ibezapolstat will now move forward to Phase III clinical trials. Further data will be provided when available on all of the secondary and exploratory endpoints in the Phase IIb trial, including sustained clinical cure, extended clinical cure up to 94 days and the comparative impact on the microbiome. We anticipate that these secondary and exploratory endpoints will provide clear separation between these two therapeutic options and all of these endpoints will be disclosed when available over the next 90 days. The Phase IIb trial was originally designed to be a non-inferiority trial and later amended to include an interim efficacy analysis with review by an independent data monitoring committee or IDMC.
The decision to end the trial early based on the blinded clinical observations obviated the need for an interim analysis, the need for the IDMC review and the non-inferiority assessment. The company determined in consultation with its clinical and statistical experts that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating C. diff infection. We remain particularly excited about the dual impact of ibezapolstat to treat the acute C. diff infection while appropriately managing the long-term care of each patient’s microbiome, which we believe is exceptional for antibiotic therapy. Other key highlights from the third quarter or in some cases shortly thereafter, include the following.
The World Anti-Microbial Resistance Congress convened its annual meeting in Philadelphia in September 2023 where experts in the field from both the public and private sectors weighed in on the latest innovations to address antimicrobial resistance. Our Executive Chairman with us today, Bob DeLuccia, presented an update entitled, Novel DNA Pol IIIC Inhibitors for Gram-Positive Bacterial Infections: Preparing for the Next Pandemic. This presentation as well as the others that I’ll describe is available on our website acurxpharmaceuticals.com. At ID Week which convened in Boston, October 11 to 15, Acurx was featured at two scheduled events. First, an oral presentation was provided by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy, and the Principal Investigator for microbiome aspects of our ibezapolstat trial program entitled: Elucidating the Gram-Positive Selective Spectrum Activity of Ibezapolstat; Secondary Analysis from the Phase IIa trial.
Secondly, at ID Week Acurx presented at the symposium entitled New Antimicrobials in the Pipeline. At the symposium, Acurx presentation was entitled Novel DNA Pol IIIC inhibitors for Gram-Positive Bacterial Infections. Next up was the ClostPath meeting, the International Conference on Molecular Biology and Pathogenesis of Clostridia, at which there were three scientific posters presented during the conference in Banff, Canada from September 19 to 23. We provided new information supporting ibezapolstat’s unique pharmacologic profile. The first of the three was entitled ibezapolstat modulates Clostridioides difficile virulence factors in vitro showed ibezapolstat reduces toxin production by C. diff bacteria. The second entitled C. difficile In Vitro Biofilm Studies of Ibezapolstat and Comparator Antibiotics showed ibezapolstat was as effective as the currently used anti C.
diff antibiotics, fidaxomicin, vancomycin and metronidazole, reducing biofilm embedded C. difficile. The third entitled Metagenomic Evaluation of Ibezapolstat Compared to Other Anti-C. diff Agents showed ibezapolstat and fidaxomicin both caused favorable proportional increases in bacteroidetes, but distinct from vancomycin and metronidazole, which caused unfavorable proportional increases in proteobacteria. All the presentations again are available on our website. And now back to our CFO, Rob Shawah to guide you through the highlights of our financial results for the third quarter of 2023. Rob?
Robert Shawah: Thanks, Dave. Our financial results for the third quarter ended September 30, 2023 were included in our press release issued earlier this morning. The company ended the third quarter with cash totaling $7.1 million compared to $9.1 million, as of December 31, 2022. I’ll also note that subsequent to the quarter to the September 30, we did receive $2.2 million in cash from warrant conversions in October of 2023. Research and development expenses for the three months ended September 30, 2023 were $1.3 million compared to $1.6 million for the three months ended September 30, 2022. The decrease was due to the timing of Phase IIb trial related costs. For the nine months ended September 30, 2023, research and development expenses were $4.1 million versus $3.3 million for the nine months ended September 30, 2022.
The increase is due primarily to Phase IIb trial related costs and an increase in consulting costs. General and administrative expenses for the three months ended September 30, 2023 were $1.8 million compared to $2 million for the three months ended September 30, 2022. The decrease was due primarily to a $0.2 million decrease in professional fees. For the nine months ended September 30, 2023, general and administrative expenses were $5.4 million versus $5.5 million for the nine months ended September 30, 2022. The amounts reflect a decrease in professional fees of $0.3 million, offset by an increase of $0.2 million in share-based compensation. The company reported a net loss of $3.1 million or $0.24 per diluted share for the three months ended September 30, 2023, compared to a net loss of $3.5 million or $0.32 per diluted share for the three months ended September 30, 2022, and a net loss of $9.5 million or $0.77 per share for the nine months ended September 30, 2023, compared to a net loss of $8.8 million or $0.84 per diluted share for the nine months ended September 30, 2022, all for the reasons previously mentioned.
The company had 13,005,128 shares outstanding as of September 30, 2023. With that, I’ll turn the call back over to Dave. Dave?
David Luci: Thanks, Rob and to all of you joining us today. We outlined advances in several areas that we believe will spur continued momentum and growth to build on our strong fundamentals. We look forward to sustaining this momentum even during these challenging times and sharing future updates in the coming months. Now in advance of our customary Q&A, I’ll ask my Co-Founder and Executive Chairman, Bob DeLuccia to provide his perspective given Bob manages our research and development programs, including the recently completed Phase II clinical trial. Bob?
Robert DeLuccia: Thanks, Dave and thanks for updating our stakeholders on our recent progress and thanks to all for your continuing support to reach this important clinical development milestone, which takes ibezapolstat one step closer to commercialization for CDI patients in need of a promising new antibiotic with a novel bactericidal mechanism of action. And this is especially important in this age of emerging antimicrobial resistance to the currently used antibiotics. So from my perspective, we now have robust scientific evidence to present a strong data package to FDA for an end of Phase II meeting. The outcome of this meeting will confirm our readiness to advance the Phase III clinical trials with specifics on trial design and patient enrollment targets.
At the same time, we’ll submit our plans to the European Medicines Agency for conducting Phase III clinical trials outside the United States and we expect to have their guidance around midyear next year. Bottom line is, I think we have a new antibiotic, which is first in a new class and fast tracked by the FDA. It’s fully patented. It has regulatory exclusivity 10 years post market introduction in the U.S. as well. It works extremely well. It’s clinically comparable to the standard of care after 10 days old treatment in a serious and potentially life-threatening infection that demands antibiotic treatment. From what we’ve seen so far, we expect to further demonstrate favorable effects on the microbiome and less recurrence of infection. It’s also very well-tolerated and efficient to manufacture, so we can be cost-competitive in the marketplace.
Now since we’ll be the only C. diff antibiotic beginning Phase III next year, assuming success, we’ll be next up at that for approval and market introduction in the U.S. and countries outside the United States. In my over 50 years’ experience in antibiotic development and marketing, I think I’ve got a good rearview mirror that gives me a clear vision and a pathway forward to deliver a winner here, not only for patients with C. diff infection, but in general, for better public health and of course, for our shareholders. In my opinion, simply put, ibezapolstat kills the bug and preserves the microbiome. And back to you, Dave.
David Luci: Thank you, Bob. I’ll now open the call for questions. Operator?
Operator: Thank you. Ladies and gentlemen, we will now be conducting a question-and-answer session. [Operator Instructions] Our first question is from Jason McCarthy with Maxim Group. Please go ahead.
Michael Okunewitch: Hey, guys. How is it going? This is Michael Okunewitch on the line for Jason. And first off, I’d like to congratulate you on the progress.
David Luci: Thank you, Michael.
Michael Okunewitch: So I guess to start off, I’d like to for you to give us a bit more of an idea of what you’re thinking ahead of the end of Phase II meeting in terms of what a Phase III program could look like in terms of size and scope, potential costs? And then also if you would still be targeting non-inferiority as a primary endpoint. Can you just give me your thoughts on that?
David Luci: Sure. And yes, we would still be targeting non-inferiority to the control arm, which would be oral vancomycin, much like Summit did most recently in its effort to get an antibiotic approved to treat C. diff. What we’re looking at is we’re looking at two clinical trials in Phase III, two registration trials. And we’re considering, and all of this is preliminary, as you know, but we’re considering an imbalanced approach pursuant to which we would have fewer patients in the first trial and more patients in the second trial, so that we could potentially raise money to fund the smaller first trial. And with continued good data in hand, non-inferiority in this case for a Phase III registration trial, we would hope to see an uptick in our share price and use that uptick to raise money for the second trial.
Keeping in mind that this sequential approach is very possible for us because we have 10 years of market exclusivity with our new molecular entity status and QIDP. So I think that’s what we would do. I think the first trial I think we would ballpark figures, we would try to have a 2:1 randomization potentially and preliminarily. If that gets through our science team and the FDA, it might look something like 133 patients on ibezapolstat and 66 on oral vancomycin. So it would be a much more discrete trial that I think a lot of people are thinking. So to pay for it won’t, for a small company won’t be that challenging.
Michael Okunewitch: All right. Thank you for that. And then one more for me and I’ll hop in the queue. Just as we’re getting up to those secondary analysis, could you talk a little bit about what you’re looking for specifically in terms of clinically relevant separation from Vanco? What kind of threshold do we need to reach in those secondary end points?
David Luci: So we think that the microbiome advantage is the key advantage because that’s the thing that most antibiotics don’t do. So if we can address the acute infection, while at the same time, fully restoring a healthy microbiome to baseline, that’s something which I don’t know of any other antibiotic that’s able to do that. We’re still studying the mechanism of action to see how that’s done. But I think that provides clear separation by itself. We’re also the only folks that have gone out formally 94 days for antibiotics and C. diff at least, to see that there are no reinfections that far out. So I’m particularly excited about that 94-day out data to see in a subset of patients how many patients of ours are reinfections 94 days out compared to vancomycin.
So those are two real exciting pieces. And what we’re going to do since all of the secondary and exploratory endpoints are so material from a corporate level perspective, and we don’t want to be holding material non-public information for any sort of period of time for the SEC purpose. So we’ll be getting the data out as it comes in, the sustained clinical cure, the extended clinical cure and of course the microbiome comparison. We won’t wait for it to be all together, and we’ll get it out as we receive it.
Michael Okunewitch: All right. Thank you very much.
David Luci: Thank you, Michael.
Operator: Thank you. Our next question is from Ed Arce with H.C. Wainwright. Please go ahead.
Thomas Yip: Hi. Good morning, everyone. This is Thomas Yip asking the [indiscernible] questions for Ed. Thank you for taking the questions. So perhaps first question, I believe you touched on it a little bit. When can we expect to see more Phase II data? Will this be in a purification — or will this be around major medical companies?
David Luci: I’m sorry, when can you expect to see the secondary endpoint information?
Thomas Yip: Yes. That’s right. This additional Phase II data additional analysis.
David Luci: I see. Okay. So we’ll have a first press — in terms — I’ll start out with the press release disclosure and then I’ll turn it over to Bob DeLuccia for the scientific conference disclosure. I think some of that is still a bit up in the air. But on the press releases, we’ll very likely come out with the first press release on sustained clinical cure in December. In either December or January, we’ll have the 94-day out data, the extended clinical cure data. And in January or February, we’ll have the data on the microbiome. Then, of course, in March, we’ll have the meeting with the FDA, and we’ll have a press release around that too after it’s completed. But Bob, did you want to mention the scientific presentations with the Phase IIb data?
Robert DeLuccia: Yeah. I think with some of the data we targeted in early next year as it becomes available, as Dave said. But concurrently, as we get the final study report, we’ll be preparing the data for publication as well.
Thomas Yip: Great. Thank you. We definitely look forward to that. Perhaps just one more question from us. This one is financial. You mentioned a little earlier Phase III is expected to be conducted in a sequential manner. Can you provide some preliminary thoughts, estimates on estimated costs for this first Phase III study? And what are some options to move forward this initial Phase III study?
David Luci: Yeah. I mean we have — we’re going to unveil our detailed plan in coming weeks. We think the first of the two trials, and again, this depends on the data and as you know, it is preliminary. But the first of the two trials will probably range between $20 million and $25 million. So right now, as we sit here with between $9 million and $9.5 million and we have about another $15 million in warrant exercises, which after more successful data is announced, we expect to see some of that coming in, in terms of cash for the warrant shares. But beyond that, we don’t have a very heavy lift and we have a detailed plan. And what I can tell you is it’s going to be as non-dilutive as humanly possible.
Thomas Yip: Understood. Thank you again for taking our questions. Looking forward to your updates in the next coming months.
David Luci: Very good. Well, thank you, Tom. Assume that and thanks to Ed as well.
Operator: Thank you. Our next question is from the line of James Molloy with Alliance Global Partners. Please go ahead.
James Molloy: Hi. Good morning. Thank you very much taking my questions. Could you walk us through a little bit, maybe a little competitive analysis where Summit their failure in ’21, but Dave said back in 11 (ph) obviously with the approval. Can you walk through a little bit to sort of the dosing, the reinfection rate what Summit did wrong with what Merck and Cubist did right on deficit and how that ties into ibezapolstat and what you guys are hoping to do here in your Phase III?
David Luci: Sure. The Merck example is the most clear example because they — Merck’s predecessor Optimer went to Phase III with 15 out of 16 cures in an open-label trial. We have 15 of 16 in IIb and another 10 of 10 in IIa. So we’re going at 25 of 26. So as Bob mentioned, it’s a robust package and is supplemented by our manufacturing, preclinical and other data. So we’re delighted with that and we’re following a successful pathway with the fidaxomicin pathway. What others have done wrong, so Summit Therapeutics, you mentioned, they conducted a superiority trial, as I understand it, and it wasn’t involved. But from what I gather from the public disclosure, they enrolled quite well through COVID at around 169 trial sites internationally.
And we like that model for our Phase III, which we expect to be international as well. And you can see their sites on clinicaltrial.gov. But they had a superiority trial. And while they are conducting that trial, Jim, they actually try — they changed their primary endpoint and unblinded the data and took a look. And only after that did they go to the FDA to try to get the FDA to kind of ratify what they did, and the FDA wasn’t comfortable with that. So I don’t know exactly how that series of decisions kind of happened. We didn’t do that. We contacted the FDA prior to ending the Phase IIb trial to make sure that everything was copacetic and they were very good at getting back to us quickly. And we also reached out and contacted our independent data monitoring committee and our Scientific Advisory Board to make sure that we are in unanimous agreement that this was the right decision.
And certainly, we think it was. So that’s kind of like an alternative to how Summit kind of ran their Phase III. So the thing about Summit’s Phase III that we like is the pace of their enrollment. I think they got about 750 patients internationally in about two years’ time. Our first study will be, I think, somewhere in the neighborhood of 200-ish.
James Molloy: Understood. And also, one of the — you talked about the healthy microbiome with the ibezapolstat, I know — again, not to pile on some of what, they are most recent relevant company to look at. They were talking about the microbiome and their data as well and obviously didn’t help them very much. How do you quantify sort of a healthy microbiome? And how much do you think that plays into the FDA’s decision vis-a-vis just really being non-inferior to Vanco?
David Luci: I think it’s a burgeoning fast-growing kind of business sector, the microbiome. And the reason why it’s so important is because when you have an imbalanced microbiome, just generally outside of C. diff, it leads to disease, whether it’s cancer or C. diff or diabetes, all kinds of things are triggered as we find more and more by an imbalanced microbiome. Now in terms of C. diff, the primary cause of reinfections is an imbalanced microbiome, right? And the C. diff reinfection market is best estimate $4.7 billion a year in the U.S. So if you can restore a healthy microbiome, you’re basically able to make a very nice dent in the public health cost in the recurrent C. Diff market. So we think that’s going to play an important role.
And it’s going to distinguish us from a broad spectrum antibiotic like oral vanc, which has — it just decimates the microbiome because it’s a broad spectrum. I think oral vanc was approved in 1986 to treat C. diff because there was so little out there that was useful to treat C. diff. It wasn’t that it was the best tool because it’s broad spectrum, not narrow spectrum, but there was just such a need that it got the approval and its first approval was in 1958. I hope that answers your question.
James Molloy: It does indeed. And just a couple of questions, if I could, please. Any updates on the PASTEUR Act?
David Luci: We haven’t had any updates on the PASTEUR Act specifically. We understand there’s a number of different legislative options out there that are being considered. But the more I watch Washington, the more I realize that I have no idea what’s going on. I mean, it looks like we’re coming up to another government shutdown. And I’m sure nobody is thinking ahead of the holidays. They’re trying to keep the government open right now.
James Molloy: Okay. Maybe just a last question for Robert. Keeping a close eye on the accrued expenses here in the third quarter. Can you walk us through what the 82% of the [indiscernible] vendor are on that, please?
David Luci: Rob, do you want to?
Robert Shawah: Yes, that’s our clinical research organization. Yes.
Robert DeLuccia: Our CRO, yes.
James Molloy: Great. Thanks for taking the questions.
David Luci: Thank you, Jim.
Operator: Thank you. Our next question is from the line of John Stinton (ph) an Investor. Please go ahead.
Unidentified Participant: Thank you for taking my questions.
David Luci: Good morning, John.
Unidentified Participant: Can you hear me now?
David Luci: Yes. I can hear you.
Unidentified Participant: Right. So with regard to the 94-day study, is it possible that, that study when fully digested will prove clinical superiority rather than non-inferiority?
David Luci: There will be numbers that people can interpret, but it won’t be statistically driven.
Robert DeLuccia: Correct. You’re right, Dave.
Unidentified Participant: Okay. Then follow-up is the original Phase IIa and b studies, you said were to prove non-inferiority, was it your expectation at the time that it would indeed prove clinically superior? And was that a disappointment that it did not or was that just not something you were measuring at all?
David Luci: Well, originally, that was the plan, to measure for statistical noninferiority, and if proven, to test for superiority. But just like with the independent data monitoring committee mechanism, those mechanisms kind of got put to bed when we decided to end the Phase IIb trial early because there are so few patients evaluable in the IIb. There was no mathematical mechanism to measure for non-inferiority or superiority. So in Phase II, unlike registration in Phase III trials, you need to establish clinical comparability to move on to Phase III. So we decided that since we are looking at the blinded data and it looks so positive, you could see how many failures there were, or in our case, there were not, that it was certain to us that we would be able to establish clinical comparability and move on to Phase III.
So we didn’t want to — for a number of reasons, we didn’t want to waste the time, the money and not have our drug at market as soon as possible. We figured we have a win on the table here, let’s take it off the table and move on.
Unidentified Participant: Okay. Thank you. One last question is since October 2, we’ve had some very wild swings in the price of this Acurx with the company with some days as many as and exceeding 8 million — almost 10 million shares being traded in a single day, which is pretty unusual. Do you have any comments on that?
David Luci: No. I mean, we came out with data, right? So we’re going to be coming out with even more data. Three to five solid press releases in the next kind of period of time ending at the end of the first quarter. So we expect to have a lot more high-volume days between now and the end of the first quarter. I will note that as part of the corporate maturation process, this is what happens. At the end of 2022, we were trading about 21,000 shares a day, if you recall, average daily trading volume. So now as you look at it in the rearview mirror, as Bob says, we’re now entering kind of the mid-life of microcap pharmaceutical company. And as we become Phase III ready in every sense, it’s – we expect the trend to continue.
What I like about it and what I will say as well, I like the notion that it seems to me, and this will be coming out more and more through public filings of our ownership. It seems to me that more and more of our shares are entering institutional hands, which is another thing that’s very healthy for the company.
Unidentified Participant: All right. Thank you.
David Luci: Thank you, John.
Operator: Thank you. Our next question is from the line of Ryan Mulholland (ph) with 50-50 LLC (ph). Please go ahead.
Unidentified Participant: Hi, David. Thank you very much for taking the time. Just a couple of questions. One regarding the Phase IIb trial and the randomization. Was that a block randomization that was used? And are we to assume that the two incomplete participants were then from the vancomycin arm? And then second question — you can go for it.
David Luci: Yeah. I was just going to say, I don’t know what a block randomization is, and I wouldn’t assume — I don’t know the two protocol violators, I don’t know which arm they were in. What I can tell you is that the randomization in the IIb was done at the local level as opposed to a centralized randomization. So I think that means it’s not a block randomization. But I’m not entirely sure where the two protocol vials have come out.
Unidentified Participant: Okay. Thank you. Do you know if that information will be forthcoming?
David Luci: I mean, I don’t expect to know. I haven’t asked because they’re protocol violators. So there’s nothing that I can assume if I had that information. So I don’t even think I asked, so the numbers are not evaluated.
Unidentified Participant: And then lastly, over the past year you’ve had several discussions, several interviews where you have discussed potential M&A participation and your kind of interest in not taking maybe ibezapolstat over to Phase III yourself, but finding a partner. Is that still something that’s on your radar? And are there interesting parties who have signed NDAs to investigate that interest on their own?
David Luci: Yes. So there’s a lot to bite off there. But yes, we do have NDAs signed in some cases, with interested parties. They being confidential, I can’t tell you the names. And yes, M&A is definitely on our calendar for 2024. We think sharing risk with a big pharma partner for Phase III in the commercial period is a prudent idea. Now it takes two parties to create a deal. I’m not certain whether or not a deal will come to fruition. And we won’t know what our value is until we unveil and find out what the secondary and exploratory endpoints are from the recently completed trial. So we kind of have to have that information in order to formally launch that process. But in the first quarter of the year, I’m sure we’ll formally start the process with an asterisk that if we were to get a term sheet in the meantime, then we would be forced — if they were within the ballpark that the Board of Directors find generally interesting, then they may form a special committee and have us move forward earlier than we expected.
But that’s about it. So for now, I would just refer you to the most recent deals in the C. diff space that have been consummated. And you can kind of get an idea of what evaluations are like. So one deal from November 2020 was when Astellas sold European rights to fidaxomicin, to Tillotts Pharma AG in Europe. And another deal was the Destiny Pharma deal with Sebela Pharmaceuticals, which look big, $540 million, but that was only $1 million upfront and the $540 million of all of that money isn’t payable until the very end of the marketing period, which, I don’t know, might be 15 or 20 years out. So those are the comparables that we see in the space. And we’ll look at our data. And hopefully our data shows a clear separation and we’re able to get something done in terms of M&A in 2024.
And we’ll be working on a parallel track with Phase III preparation, and we’ll see how far we get with each.
Unidentified Participant: Thank you and your team. I appreciate all your efforts and it’s a pretty great product you put out there.
David Luci: Thank you, Ryan.
Operator: Thank you. As there are no further questions, I would now hand the conference over to Dave Luci for his closing comments.
David Luci: Thank you very much, Ryan. We’re pleased for all of you coming to the conference today and expressing your thoughts and questions and we look forward to updating you soon. Let’s sit tight and buckle up and 2024 is going to be a great year, we expect. Thank you.
Operator: Thank you. The conference of Acurx Pharmaceuticals has now concluded. Thank you for your participation. You may now disconnect your lines.
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Acurx conference call (Nov 14, 2023) --->
Some additional info from the Acurx conference call. Luci said that the durability and microbiome data from the Phase 2b will be released as the company gets it in the weeks and months ahead (see below), rather than all at once at the end. Here is his approx timeline for the news flow -
Dec ------------ Sustained Clinical Cure data
Dec or Jan --- Extended Clinical Cure data up to 94 days
Jan or Feb --- Impact on Microbiome data
March --------- End of Phase 2 meeting with FDA
On the partnership / M+A front, Luci said they have some NDAs (plural). As I understand it, an NDA is a Non-Disclosure Agreement, which (I think) allows sharing of non-public info like clinical data between Acurx and interested pharmas.
Luci has clearly said (in July) that he favors an M+A or partnering deal prior to the Phase 3s, and from the conf call it sounds like this process will advance in 2024 as the additional data becomes available. So a lot will probably depend upon the strength of the upcoming durability and microbiome data, the number of interested pharmas, etc.
With the Phase 3s, they will need two, and Luci said they are favoring (if possible) a smaller first Phase 3 trial, and then a larger second Phase 3. The first Phase 3 would be approx 200 patients (133 getting Ibez and 66 getting Vanc), and would likely cost in the $20-25 mil range, and will include some international sites, and will be a non-inferiority trial. He said the advantage of a smaller first Phase 3 is that it would be cheaper and faster, and should provide more than enough data to get an M+A or pharma deal (assuming good data of course). Ideally though, Luci said (in July) that he prefers doing a deal prior to Phase 3.
On the funding / cash side, he said they now have $9 mil range, and up to $15 mil potentially coming from the exercising of warrants. Luci says he wants to proceed - 'as non-dilutively as is humanly possible'.
Concerning the Pasteur Act, he said that he isn't expecting anything happening soon (is awaiting Congressional approval) since the government is currently in such disarray.
Anyway, this info is from my notes, so you may want to verify by listening to the conference call -
877-660-6853, and conf call code is - 13742354
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>>> Acurx Pharmaceuticals, Inc. Reports Third Quarter 2023 Results and Provides Business Update
November 14, 2023
https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-third-120100928.html
STATEN ISLAND, N.Y., Nov. 14, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the third quarter ended September 30, 2023.
Highlights of the third quarter ended September 30, 2023, and in some cases shortly thereafter, include:
On October 2, 2023, Acurx ended enrollment in its Phase 2b clinical trial of ibezapolstat, its lead antibiotic candidate, for the treatment of patients with C. difficile infection, or CDI;
On November 2, 2023, Acurx reported top-line data from the Phase 2 clinical trial including the ibezapolstat clinical cure rate at end of treatment, or EOT, of 96% (25/26) including 100% in Phase 2a (10/10) and 94% in Phase 2b (15/16) as well as the cure rate for oral vancomycin at EOT of 100% (14/14);
Ibezapolstat will now move forward to Phase 3 clinical trials. Preparation underway for End-of-Phase 2 FDA Meeting and advancement to Phase 3
No safety concerns were reported in either arm of the Phase 2b clinical trial or in the Phase 2a open label trial;
In consultation with its scientific advisors, the Company determined that clear evidence of clinical cure was established with ibezapolstat and ibezapolstat is clinically comparable to vancomycin, the standard of care to treat CDI;
Further data will be provided when available on all of the secondary and exploratory endpoints in the Phase 2b trial, including sustained clinical cure data, extended clinical cure data up to 94 days and impact on the microbiome when compared to vancomycin.
The Company anticipates that these secondary and exploratory endpoints will provide clear separation between these two therapeutic options and provide validation for front-line use of ibezapolstat to treat patients with CDI;.
In September 2023, the World Antimicrobial Resistance (AMR) Congress convened its annual meeting in Philadelphia where experts in the field from both the public and private sectors weighed in on the latest innovations to address AMR. Our Executive Chairman, Bob DeLuccia, presented an update entitled: "Novel DNA pol IIIC Inhibitors for Gram-positive Bacterial Infections: Preparing for the Next Pandemic".
The IDSA (Infectious Diseases Society of America) convened its annual meeting, called ID Week, in Boston from October 11-15, 2023. Acurx was featured at two scheduled events:
First, an oral presentation by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy, and the Principal Investigator for microbiome aspects of our ibezapolstat clinical trial program, was given on October 14 entitled: Elucidating the Gram-Positive Selective Spectrum Activity of Ibezapolstat; Secondary Analysis from the phase 2a trial.
Second, Acurx presented at the symposium entitled, "New Antimicrobials in the Pipeline" on October 12. At the symposium, Acurx presentation was entitled: "Novel DNA pol IIIC Inhibitors for Gram-positive Bacterial Infections."
Three scientific posters were presented during the CLOSTPATH conference held in Banff, Canada from September 19 to 23, 2023 and provided new information further supporting ibezapolstat's unique pharmacologic profile:
The first entitled: "Ibezapolstat modulates Clostridioides difficile virulence factors in vitro" showed Ibezapolstat reduces toxin production by the C. difficile bacteria…
The second entitled: "C. difficile In Vitro Biofilm Studies of Ibezapolstat And Comparator Antibiotics" showed ibezapolstat was as effective as the currently-used anti-C. difficile antibiotics fidaxomicin, vancomycin and metronidazole in reducing reduce biofilm-embedded C. difficile…
The third entitled: "Metagenomic Evaluation of Ibezapolstat Compared to Other Anti-C. difficile Agents" showed ibezapolstat and fidaxomicin both caused favorable proportional increases in Bacteroidetes but distinct from vancomycin and metronidazole, which caused unfavorable proportional increases in Proteobacteria.
All the presentations described above are available on our website.
Third Quarter 2023 Financial Results
Cash Position:
The Company ended the third quarter with cash totaling $7.1 million, compared to $9.1 million as of December 31, 2022. After the quarter end, the Company received an additional $2.2 million in cash associated with the conversion of approximately 680,000 warrants, which resulted in the issuance of approximately 680,000 shares.
R&D Expenses:
Research and development expenses for the three months ended September 30, 2023, were $1.3 million compared to $1.6 million for the three months ended September 30, 2022. The decrease was due to the timing of Phase 2b trial related costs. For the nine months ended September 30, 2023, research and development expenses were $4.1 million versus $3.3 million for the nine months ended September 30, 2022. The increase is due primarily to Phase 2b trial related costs and an increase in consulting costs.
G&A Expenses:
General and administrative expenses for the three months ended September 30, 2023, were $1.8 million compared to $2.0 million for the three months ended September 30, 2022. The decrease was due primarily to a $0.2 million decrease in professional fees. For the nine months ended September 30, 2023, general and administrative expenses were $5.4 million versus $5.5 million for the nine months ended September 30, 2022. The amounts reflect a decrease in professional fees of $0.3 million, offset by an increase of $0.2 million in share-based compensation.
Net Loss:
The Company reported a net loss of $3.1 million or $0.24 per diluted share for the three months ended September 30, 2023 compared to a net loss of $3.5 million or $0.32 per diluted share for the three months ended September 30, 2022, and a net loss of $9.5 million or $0.77 per share for the nine months ended September 30, 2023, compared to a net loss of $8.8 million or $0.84 per diluted share for the nine months ended September 30, 2022 for the reasons previously mentioned.
The Company had 13,005,128 shares outstanding as of September 30, 2023.
Conference Call
As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:
Date:
Tuesday, November 14, 2023
Time:
8:00 a.m. ET
Toll free (U.S. and International):
877-790-1503
Conference ID:
13742354
About the Ibezapolstat Phase 2 Clinical Trial
On November 2, 2023, we reported top-line data from the Phase 2 clinical trial including the ibezapolstat clinical cure rate at end of treatment, or EOT, of 96% (25/26) including 100% in Phase 2a (10/10) and 94% in Phase 2b (15/16) as well as the cure rate for oral vancomycin at EOT of 100% (14/14). No safety concerns were reported in either arm of the Phase 2b clinical trial or in the Phase 2a open label trial. In consultation with its scientific advisors, the Company has determined that clear evidence of clinical cure has been established with ibezapolstat and is clinically comparable to vancomycin. Ibezapolstat will now move forward to Phase 3 clinical trials. Further data will be provided when available on all of the secondary and exploratory endpoints in the Phase 2b trial, including sustained clinical cure data, extended clinical cure data up to 94 days and impact on the microbiome compared to vancomycin.We anticipate that these secondary and exploratory endpoints will provide clear separation between these two therapeutic options.
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542).
This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. This Phase 2 clinical trial will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy.
Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200;
doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes early-stage antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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With Acurx, here's what Dew had to say about the company when I asked him several weeks ago (link below). He makes some excellent points about the dwindling cash level, as well as the potential for warrants being exercised soon, which could bring in some cash -
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=173027440
The CEO Luci is a finance guy, and they did a $4 mil money raise in May, and a similar one in 2022. Acurx was also in the running for approx $11 mil in funding for a pre-clinical stage program, but that fell through in August -
>>> The Company was notified by CARB-X that its application for a non-dilutive grant to fund its pre-clinical antibiotic candidate, ACX375C, was not approved. CARB-X noted that the 2023 round of funding was very competitive and that their Scientific Advisory Board was enthusiastic about pol IIIC as the bacterial target of our molecules and that the sufficiently good PK and safety properties of the compounds justified the proposed lead optimization plan. CARB-X encouraged us to re-apply for potential future requests for proposals or RFPs that CARB-X will continue to promulgate from time to time for CARB-X funding consideration. <<<
https://www.acurxpharma.com/news-media/press-releases/detail/60/acurx-pharmaceuticals-inc-reports-second-quarter-2023
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>>> Acurx Announces Positive Top-Line Ibezapolstat Phase 2 Efficacy Results with 96% Clinical Cure Rate in Patients with C. difficile Infection
PR Newswire
November 2, 2023
https://finance.yahoo.com/news/acurx-announces-positive-top-line-110100342.html
In a total of 26 ibezapolstat-treated patients in Phases 2a and 2b, the Clinical Cure rate is 96%
Meets protocol primary objective of assessing the primary efficacy endpoint of the Clinical Cure rate after 10 days of oral treatment
Ibezapolstat was well tolerated; no drug-related Serious Adverse Events
Further analyses forthcoming regarding secondary and exploratory endpoints, including Sustained Clinical Cure data, Extended Clinical Cure data up to 94 days and comparative effects on gut microbiome
Preparation underway for End-of-Phase 2 FDA Meeting and advancement to Phase 3
Ibezapolstat has previously received FDA Qualified Infectious Disease Product and Fast-Track Designation
Management will be available for Q&A on November 14, 2023 earnings call https://www.acurxpharma.com/news-media/press-releases/detail/65/acurx-pharmaceuticals-to-discuss-third-quarter-2023
STATEN ISLAND, N.Y., Nov. 2, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced efficacy results from the Phase 2 clinical trial (Phase 2a segment and Phase 2b segment) of ibezapolstat for the treatment of C. difficile Infection (CDI).
The Company previously announced that it decided to terminate the Phase 2b vancomycin-controlled trial segment early based on aggregate blinded data showing a high observed clinical cure rate with no emerging safety concerns. The Company made this decision in consultation with its medical and scientific advisors based on the compelling clinical observation that the clinical cure rate for ibezapolstat was projected to be at least 90% pooled across the open-label Phase 2a and the blinded Phase 2b segments with no safety concerns noted. Other factors also influenced the decision, including the cost of maintaining clinical trial sites and the challenging enrollment environment in the U.S. due to the COVID-19 pandemic and its aftermath.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
The overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced clinical cure. The Company is confident that based on the pooled Phase 2 ibezapolstat clinical cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October, 2022).
According to Stuart Johnson, MD, Professor of Medicine, Loyola University (Infectious Disease) and Acurx Scientific Advisory Board member: "I am very encouraged by the accumulating data showing that ibezapolstat is clinically comparable to vancomycin in treating CDI. Since there is only one other antibiotic besides vancomycin approved for treatment of this serious disease, there is a clear need for more first-line therapeutic agents in our armamentarium. Moreover, the advancement of a small synthetic molecule with a novel bactericidal mechanism to treat CDI is especially important in this era of emerging antimicrobial resistance. I am very supportive of the decision by the Company to end the Phase 2 trial and plan for Phase 3."
Kevin Garey, PharmD, MS, Professor and Chair, University of Houston College of Pharmacy, the Principal Investigator for microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member stated: "These results confirm and extend our data from the open-label component of the Phase 2 study and demonstrate the potent activity of ibezapolstat against C. difficile. I anticipate our ongoing microbiome studies will confirm the microbiologic eradication of C. difficile and also compare microbiome changes to advance knowledge of anti-CDI recurrence properties of ibezapolstat. Our previous data showed that ibezapolstat unexpectedly spares other Firmicutes along with the important Actinobacteria phylum necessary for maintaining a healthy microbiome. These characteristics, in conjunction with ibezapolstat's ability to favorably increase the ratio of secondary-to-primary bile acids in the colon, suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to standard of care vancomycin."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These ibezapolstat observed clinical cure rate results are impressive for an investigational antibiotic in a Phase 2 trial for CDI. They greatly enhance our scientific evidence base and, in our view, provide robust support for an anticipated End-of-Phase 2 FDA Meeting to occur towards end of first quarter next year with advancement into Phase 3 clinical trials to follow. Additional analyses of secondary and exploratory endpoints of the Phase 2b clinical trial will be forthcoming as soon as available and will include: Sustained and Extended Clinical Cure rates up to 94 days, systemic exposure to ibezapolstat, comparative effects on gut microbiome and, patient reported outcomes."
Mr. DeLuccia added: "I thank all of our clinical trial investigators and their staffs and patients who participated in the trial, as well as all our stakeholders whose support contributed to reaching this important clinical development milestone which is one step closer to commercialization for patients-in-need of a promising new class of antibiotic for treatment of CDI."
David P. Luci, the Company's President and Chief Executive Officer, stated: "Ultimately the marketplace will determine the antibiotic of choice for front-line treatment of CDI. But, in our view, as we plan to enter Phase 3 pivotal clinical trials, ibezapolstat appears to have the properties for ultimate competitive advantage including high clinical cure rates, low recurrent infection, minimal microbiome disruption and manufacturing efficiencies to allow competitive pricing. We believe the market will recognize and appreciate these advantages."
The Company recognizes the month of November as C. difficile Awareness Month as designated by the US Centers for Disease Control and Prevention (CDC) and supports the work of the Peggy Lillis Foundation and the C Diff Foundation in raising awareness, educating and advocating for the Prevention, Treatments, Clinical Trials, and Environmental Safety of Clostridioides difficile (C. difficile) Infections worldwide. Please visit their websites:
Peggy Lillis Foundation: https://cdiff.org/
Cdiff Foundation: https://cdifffoundation.org/.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti- recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. The Company's Scientific Advisory Board concurred with this recommendation.
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19. The Company has determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee will not be required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipates that this decision will allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind.
In the Phase 2 clinical trial, the Company will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care-associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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>>> Acurx Announces Ibezapolstat Scientific Posters and Presentations at ClostPath 2023 and IDWeek 2023 Scientific Conferences
PR Newswire
October 19, 2023
https://finance.yahoo.com/news/acurx-announces-ibezapolstat-scientific-posters-110100090.html
Three scientific posters highlighting novel anti-virulence pharmacologic properties of oral ibezapolstat for C. difficile Infection; effects on toxin production, biofilm and the gut microbiome
A podium presentation entitled First of a New Class of Antibiotics (pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens; Preparing for the Next Pandemic: Antimicrobial Resistance in Gram-positive Bacterial Infections
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Oct. 19, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced three scientific posters were presented during the 13th International Conference on Molecular Biology and Pathogenesis of Clostridia (ClostPath) held in Banff, Canada from September 19 to 23, 2023. Additionally, two podium presentations were made at the Infectious Disease Society of America (IDSA) IDWeek™ 2023 Conference held October 11-15, 2023 in Boston, MA. Highlights of each are shown below.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "In light of our recent decision to discontinue the Phase 2b ibezapolstat clinical trial earlier than planned and prepare for Phase 3 clinical trials, the new information contained in these scientific posters and presentations at these conferences will add to our evidence-based briefing package for an End of Phase 2 FDA meeting planned for in the first half of next year." He also added: "We are currently compiling and verifying all data from the Phase 2b trial and we will report topline clinical efficacy for the primary clinical endpoint and safety data in the coming weeks, with other outcome data available later this year".
ClostPath:
Ibezapolstat modulates Clostridioides difficile virulence factors in vitro
Presented by Eugenie Basseres, et al; University of Houston College of Pharmacy
Ibezapolstat reduces toxin production by C. difficile
C. difficile In Vitro Biofilm Studies of Ibezapolstat And Comparator Antibiotics
Presented by M. Jahangir Alam et al; University of Houston College of Pharmacy
Ibezapolstat was as effective as the currently-used anti-C. difficile agents fidaxomicin, vancomycin and metronidazole to reduce biofilm-embedded C. difficile quantity and biofilm biomass
Metagenomic Evaluation of Ibezapolstat Compared to Other Anti-Clostridioides difficile Agents
Presented by Jinhee Jo, University of Houston College of Pharmacy
Ibezapolstat and fidaxomicin caused proportional increases in Bacteroidetes distinct from vancomycin and metronidazole, which caused proportional increases in Proteobacteria
IDWeek:
First of a New Class of Antibiotics (pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens
Presented by Michael Silverman, MD, FACP, Acurx's Medical Director; at the New Antimicrobials in the Pipeline session
Among the promising data for ibezapolstat in the treatment of C. difficile are in vitro potency, anti-virulence activities, high human fecal concentrations, 100% Clinical Cure rate in a 10-patient open-label trial, favorable safety profile to date, and potentially beneficial effects on the gut microbiome
Elucidating the Gram-Positive Selective Spectrum Activity of Ibezapolstat; Secondary Analysis from the Phase 2a trial; Presented by Kevin Garey, PharmD, MS, Professor& Chair, University of Houston, School of Pharmacy
Ibezapolstat showed variable selectivity against Firmicutes helping to elucidate its narrow spectrum of activity against certain pathogenic Firmicutes including C. difficile
The posters and presentations are available on the Company's website www.acurxpharma.com.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment.
The Phase 2b clinical trial segment has been discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19. The Company has determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee will not be required to perform an interim analysis of this Phase 2b trial data as originally planned. Acurx will analyze the data and report topline efficacy results promptly. The Company anticipates that this decision will allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind.
This Phase 2 clinical trial will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. In the event noninferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About ClostPath
The ClostPath conferences, which began in 1995, have been a leading venue to bring together top scientists and clinicians studying the molecular biology of clostridia and their role in health and disease. The scientific program of ClostPath 13 included lectures by internationally recognized leaders in clostridial research and clinical practice. In addition to state-of-the-art invited talks on the most recent and exciting discoveries in the field, short oral contributions were selected from submitted abstracts. Poster presentations gave attendees the opportunity to discuss their ongoing work with a broad audience in line with the goal to bring together basic science with clinical and translational research issues.
About the IDSA and IDWeek
The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). Over 9,500 participants attended this conference in October 2022.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported. (CID, 2022)
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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Acurx Pharma -- Pasteur Act -- >>> Bennet, Young, Bipartisan House Colleagues Reintroduce Bipartisan PASTEUR Act to Fight Antimicrobial Resistance
April 27, 2023
https://www.bennet.senate.gov/public/index.cfm/2023/4/bennet-young-bipartisan-house-colleagues-reintroduce-bipartisan-pasteur-act-to-fight-antimicrobial-resistance
Bipartisan, Bicameral Legislation Would Support Development of Innovative Antibiotics to Treat Resistant Infections and Improve Appropriate Antibiotic Use
Washington, D.C. — Today, Colorado U.S. Senator Michael Bennet and U.S. Senator Todd Young (R-Ind.), alongside U.S. Representatives Scott Peters (D-Calif.), Drew Ferguson (R-Ga.), Mike Levin (D-Calif.), and Jake LaTurner (R-Kan.) reintroduced the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act to encourage innovative drug development targeting the most threatening infections, improve the appropriate use of antibiotics, and ensure domestic availability of antibiotics when needed.
“Right now, we don’t have the tools to address the threat posed by antimicrobial resistance – and infectious disease experts are warning us that it will only get worse,” said Bennet. “The bipartisan PASTEUR Act is the strongest bill ever written to strengthen antibiotic development and use. It will fix our market failures, expand the pipeline for next generation antibiotics, and save lives. We can’t sit on our hands as this public health crisis arrives – we have to act now.”
“Americans understand that we must take every reasonable and responsible measure to prevent future public health crises. Antimicrobial resistance has become a growing crisis in recent years. Market failures have resulted in a lack of needed research and development in this field which is a threat to public health. Our bill would incentivize the development of new innovative antibiotics and focus on educating health care providers on how to avoid overuse or misuse of these life-saving medications in order to slow the emergence of antibiotic-resistant pathogens,” said Young.
“Antimicrobial resistance poses a growing and significant threat to Americans’ health,” said Peters. “The PASTEUR Act will help us develop better antibiotics to counter resistant infections and help doctors ensure these drugs are used responsibly to stop the emergence of new superbugs. In the wake of the COVID-19 pandemic, we must do everything in our power to prevent the next public health crisis.”
“Antibiotics make modern medicine possible and the U.S. is at risk of losing these critical drugs. Antibiotic resistant infections are becoming more commonplace, and Congress must take action so that the foundation of modern medicine doesn’t crumble,” said Ferguson. “The PASTEUR Act brings together the public and private sectors to address these drug development market failures, increase public health preparedness, and help usher in a new era of antibiotic development. This essential legislation will also improve appropriate antibiotic use across the healthcare system while enhancing and safeguarding new antibiotic development. Simply put, we must act now to keep research and development from falling behind.”
“Each year in the United States, at least 2.8 million people become infected with pathogens that are resistant to treatment and for which advanced antimicrobials are needed. Unfortunately, as the COVID-19 pandemic made clear, our country needs stronger resources to develop those antimicrobials and prevent another global pandemic,” said Levin. “Our PASTEUR ACT empowers the Department of Health and Human Services to seek expertise on the development of antimicrobials and devise a plan to make them widely available. I thank Sen. Bennet and Rep. Ferguson for leading this bicameral, bipartisan legislation and look forward to it moving through the legislative process.”
“The COVID-19 pandemic reminded us how crucial it is for our nation to continue investing in healthcare research to prevent future public health emergencies,” said LaTurner. “America can't afford to be asleep at the wheel when it comes to the threat of antimicrobial resistance. That's why I'm proud to join my colleagues in introducing the bipartisan PASTEUR Act to bolster new antibiotic development and help medical professionals prevent the overuse of lifesaving drugs.”
According to the Centers for Disease Control and Prevention’s (CDC) Antibiotic Resistance Threats in the United States report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, and at least 35,000 people die as a result. In March 2015, the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria directed federal agencies to accelerate a coordinated, full government response to antibiotic resistance and take action to expand the ability of our health care system to prevent, identify, and respond to the infection pandemic threat posed by antimicrobial resistance. Part of this plan was to increase and incent development of innovative antimicrobial drugs to treat resistant infections. Because of severe market failures in the health care system, many of the innovative antibiotic companies doing this work have filed for bankruptcy and stopped producing their critical drugs completely.
The PASTEUR Act would address this market failure and increase public health preparedness by keeping novel antibiotics on the market and improving appropriate use across the health care system. While current contracts between the government and drug makers base payment on volume, the PASTEUR Act would establish a subscription-style model which would offer antibiotic developers an upfront payment in exchange for access to their antibiotics, encouraging innovation and ensuring our health care system is prepared to treat resistant infections.
Statements of Support
“Millions will continue to die from resistant bacteria because we are out of treatment options. Antibiotics aren't working any more for most people who contract a superbug. The science is extraordinary, it's the business model that's broken. We desperately need a new way to pay for these drugs - antibiotics, antifungals, and phage therapy. The Pasteur Act is that rare, bipartisan idea that solves an incredible problem for an affordable price,” said Professor Kevin Outterson, Boston University.
“Antibiotics play a vital role in modern medicine, and we know that preserving access to these drugs is essential to any pandemic or public health emergency response. Yet the medicines that the U.S. relies on to treat serious infections have remained largely the same for nearly 40 years and are increasingly ineffective against quickly evolving bacteria. In 2023, the U.S. has already experienced several alarming antibiotic-resistant threats—and the emergence of new superbugs will continue and will only get worse. The bipartisan PASTEUR Act has the support of a diverse group of more than 230 public health and health care organizations, because it will help us fix the broken antibiotic drug pipeline and deliver important new therapies to physicians and the patients who need them. Reintroduction of the bill is an encouraging sign that policymakers remain committed to ensuring that lifesaving antibiotics are available when Americans need them most,” said David Hyun, director of The Pew Charitable Trusts’ Antibiotic Resistance Project.
"The need for legislative solutions to address the public health challenges posed by antimicrobial resistance (AMR) has been mounting for quite some time now, and we applaud the sponsors of the PASTEUR Act for their leadership. This bill will make new novel antibiotics a reality for patients and providers and fortify our healthcare system for future generations. AMR impacts us all and protection against the increasing threats of infection is not a partisan issue. We encourage broad support and quick passage of the PASTEUR Act,” said Candace DeMatteis, Vice President of Policy, Partnership to Fight Infectious Disease.
"For decades, we have seen antimicrobial resistance (AMR) soar around the world, while the pipeline for new treatments slows to a trickle due to the broken ecosystem for antimicrobial innovation. The PASTEUR Act is an integral solution to addressing the global public health crisis of AMR. The bipartisan bill will help repair the foundational challenges of the antimicrobial marketplace and drive the development of new, innovative treatments for patients,” said Rachel King, Interim President and CEO of the Biotechnology Innovation Organization.
“Infectious diseases physicians see firsthand the devastating impact of antimicrobial-resistant infections on our patients. We urgently need novel antimicrobials and investments in antimicrobial stewardship to preserve the efficacy of these precious drugs and optimize patient outcomes. The PASTEUR Act will deliver the tools we need to protect modern medicine and strengthen our preparedness for future emergencies,” said Carlos del Rio, MD, FIDSA, President, Infectious Diseases Society of America; and Interim Dean, Emory University School of Medicine.
“For people living with cystic fibrosis, difficult-to-treat infections are an unfortunate but common occurrence, and the fear of not having enough treatment options is an all too familiar concern. There is an urgent need to pass the PASTEUR Act to help ensure availability of novel antibiotics, not only for the CF community today, but for patients everywhere who could face a public health crisis tomorrow if Congress refuses to take action now,” said Mary Dwight, Senior Vice President and Chief Policy and Advocacy Officer, Cystic Fibrosis Foundation.
“Patients with drug resistant diseases are defenseless without new treatments, many of us are fighting rare diseases and we desperately need the treatments supported by the PASTEUR Act. PASTEUR is a bill for patients, and without it, too many of us will not survive our fight and those that do are facing a reduced quality of life. The new treatments created through the PASTEUR Act could one day cure me and others fighting disease with limited or no treatment options. Until then, I wake up every day hoping the medications available do not fail me again,” said Rob Purdie, Cofounder, MyCARE (MyCology Advocacy, Research & Education).
Specifically, the PASTEUR Act would:
Establish a subscription model to encourage innovative antimicrobial drug development aimed at treating drug-resistant infections. This model will be fully delinked, meaning that participating developers would not receive income, as a part of their subscription payments, based on volume or quantity of sales.
Subscription contracts would contain terms and conditions including product availability to individuals on a government health insurance plan, supporting appropriate use, and completion of postmarketing studies. These contracts could be valued between $750 million and $3 billion.
Build on existing frameworks to improve usage of the CDC National Healthcare Safety Network, the Emerging Infections Program, and other programs to collect and report on antibiotic use and resistance data.
Include transition measures such as smaller subscription contracts to support novel antimicrobial drug developers that need a financial lifeline.
Form a Committee on Critical Need Antimicrobials, consisting of representatives from federal agencies, doctors, patients, and outside experts, to develop and implement necessary guidance regarding infections of concern, and the favored characteristics of potential treatments.
Bennet and Young first introduced the PASTEUR Act in September 2020.
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>>> Acurx Pharmaceuticals, Inc. Reports Second Quarter 2023 Results and Provides Business Update
August 14, 2023
https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-second-110100020.html
STATEN ISLAND, N.Y., Aug. 14, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the second quarter ended June 30, 2023.
Highlights of the second quarter ended June 30, 2023 include:
Acurx continues to enroll patients in its Phase 2b clinical trial, which includes 28 U.S. clinical trial sites, for patients with C. difficile infection (CDI);
The Phase 2b clinical trial will compare the efficacy of oral ibezapolstat, the Company's lead antibiotic candidate, to oral vancomycin, the current standard of care for patients with CDI;
Acurx anticipates completing enrollment of the 36 patients required for an interim review of the Phase 2b data by a newly appointed Independent Data Monitoring Committee (IDMC) in the coming months, with only 5 patients to enroll forward;
In April 2023 two presentations were made at the 33rd Annual European Congress of Clinical Microbiology and Infectious Disease (ECCMID) in Copenhagen. First, a scientific poster entitled "Novel Pharmacology and Susceptibility of Ibezapolstat Against C. difficile Isolates with Reduced Susceptibility to C. difficile-directed Antibiotics" was presented by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy, and Principal Investigator for microbiome aspects of our ibezapolstat clinical trial program. Second, Acurx Executive Chairman, Bob DeLuccia, presented an update regarding the Company's preclinical, systemic oral and IV program for treatment of other gram-positive infections caused by MRSA, VRE and DRSP at the "Pipeline Corner" featured session at ECCMID, organized by Dr. Ursula Theuretzbacher, a world-renowned microbiology expert involved in antibacterial drug research, discovery and development strategies and policies for clinical and public health needs. These presentations are available on the Company's website at www.acurxpharma.com .
Acurx announced that it has been approved for presentations in 2H 2023 at two of the most prestigious scientific conferences in our sector; namely, the World Antimicrobial Resistance Conference (Philadelphia, PA) in September 2023 as well as at ID Week sponsored by the Infectious Disease Society of America (Boston, MA) in October 2023.
The Company is continuing its R&D collaboration with Leiden University Medical Center (Holland) under a previously awarded grant from the Dutch Government of approximately $500,000 USD to further evaluate the mechanism-of-action of Acurx's inhibitors against the DNA pol IIIC enzyme, which is the bacterial target of our antibiotic pipeline for the systemic treatment (IV and oral) of gram-positive bacterial infections;
The Company was notified by CARB-X that its application for a non-dilutive grant to fund its pre-clinical antibiotic candidate, ACX375C, was not approved. CARB-X noted that the 2023 round of funding was very competitive and that their Scientific Advisory Board was enthusiastic about pol IIIC as the bacterial target of our molecules and that the sufficiently good PK and safety properties of the compounds justified the proposed lead optimization plan. CARB-X encouraged us to re-apply for potential future requests for proposals or RFPs that CARB-X will continue to promulgate from time to time for CARB-X funding consideration.
Second Quarter 2023 Financial Results
Cash Position:
The Company ended the second quarter with cash totaling $9.1 million compared to $9.1 million as of December 31, 2022.
R&D Expenses:
Research and development expenses for the three months ended June 30, 2023 were $1.7 million compared to $0.9 million for the three months ended June 30, 2022. The increase was due to an increase in Phase 2b trial related costs. For the six months ended June 30, 2023 research and development expenses were $2.8 million compared to $1.7 million for the six months ended June 30, 2022. The increase is due primarily to an increase in Phase 2b trial related costs and an increase in consulting costs.
G&A Expenses:
General and administrative expenses for the three months ended June 30, 2023 were $1.7 million compared to $1.7 million for the three months ended June 30, 2022. Professional fees decreased by $0.1 million, offset by an increase of $0.1 million in employee related compensation costs. For the six months ended June 30, 2023, general and administrative expenses were $3.6 million compared to $3.6 million for the six months ended June 30, 2022. Professional fees decreased by $0.2 million, offset by an increase of $0.2 million in employee related compensation costs.
Net Income/Loss:
The Company reported a net loss of $3.4 million or $0.28 per diluted share for the three months ended June 30, 2023, compared to a net loss of $2.6 million or $0.26 per diluted share for the three months ended June 30, 2022, and a net loss of $6.3 million or $0.53 per diluted share for the six months ended June 30, 2023, compared to a net loss of $5.3 million or $0.52 per diluted share for the six months ended June 30, 2022 for the reasons previously mentioned.
Conference Call
As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:
Date:
Monday, August 14, 2023
Time:
8:00 a.m. ET
Toll free (U.S. and International):
877-790-1503
Conference ID:
13740293
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study is now followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial is designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. In the currently enrolling Phase 2b, trial segment, patients with CDI will be enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments will be identical in appearance, dosing times, and number of capsules administered to maintain the blind. This Phase 2 clinical trial will also evaluate pharmacokinetics (PK) and microbiome changes and continue to test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes early-stage antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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Acurx CEO presentation from earlier in the year. This provides an excellent overview -
Acurx - >>> Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections
Wei-Chu Xu 1, Michael H Silverman 2, Xiang Yang Yu 2, George Wright 2, Neal Brown 2
PMID: 31221610 DOI: 10.1016/j.bmc.2019.06.017
Abstract
Despite the growing global crisis caused by antimicrobial drug resistance among pathogenic bacteria, the number of new antibiotics, especially new chemical class of antibiotics under development is insufficient to tackle the problem. Our review focuses on an emerging class of antibacterial therapeutic agents that holds a completely novel mechanism of action, namely, inhibition of bacterial DNA polymerase IIIC. The recent entry of this new class into human trials may herald the introduction of novel drugs whose novel molecular target precludes cross-resistance with existing antibiotic classes. This review therefore examines the evolution of DNA pol IIIC inhibitors from the discovery of 6-(p-hydroxyphenylazo)uracil (HPUra) in the 1960s to the development of current first-in-class N7-substituted guanine drug candidate ACX-362E, now under clinical development for the treatment of Clostridioides difficile infection.
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Acurx - >>> Here's Why We're Watching Acurx Pharmaceuticals' (NASDAQ:ACXP) Cash Burn Situation
Simply Wall St
October 8, 2023
https://finance.yahoo.com/news/heres-why-were-watching-acurx-140059801.html
There's no doubt that money can be made by owning shares of unprofitable businesses. For example, although software-as-a-service business Salesforce.com lost money for years while it grew recurring revenue, if you held shares since 2005, you'd have done very well indeed. But while history lauds those rare successes, those that fail are often forgotten; who remembers Pets.com?
So, the natural question for Acurx Pharmaceuticals (NASDAQ:ACXP) shareholders is whether they should be concerned by its rate of cash burn. For the purposes of this article, cash burn is the annual rate at which an unprofitable company spends cash to fund its growth; its negative free cash flow. Let's start with an examination of the business' cash, relative to its cash burn.
See our latest analysis for Acurx Pharmaceuticals
Does Acurx Pharmaceuticals Have A Long Cash Runway?
You can calculate a company's cash runway by dividing the amount of cash it has by the rate at which it is spending that cash. As at June 2023, Acurx Pharmaceuticals had cash of US$9.1m and no debt. Importantly, its cash burn was US$7.2m over the trailing twelve months. So it had a cash runway of approximately 15 months from June 2023. That's not too bad, but it's fair to say the end of the cash runway is in sight, unless cash burn reduces drastically. You can see how its cash balance has changed over time in the image below.
How Is Acurx Pharmaceuticals' Cash Burn Changing Over Time?
Acurx Pharmaceuticals didn't record any revenue over the last year, indicating that it's an early stage company still developing its business. Nonetheless, we can still examine its cash burn trajectory as part of our assessment of its cash burn situation. As it happens, the company's cash burn reduced by 10% over the last year, which suggests that management are maintaining a fairly steady rate of business development, albeit with a slight decrease in spending. Clearly, however, the crucial factor is whether the company will grow its business going forward. For that reason, it makes a lot of sense to take a look at our analyst forecasts for the company.
Can Acurx Pharmaceuticals Raise More Cash Easily?
Even though it has reduced its cash burn recently, shareholders should still consider how easy it would be for Acurx Pharmaceuticals to raise more cash in the future. Generally speaking, a listed business can raise new cash through issuing shares or taking on debt. Many companies end up issuing new shares to fund future growth. By looking at a company's cash burn relative to its market capitalisation, we gain insight on how much shareholders would be diluted if the company needed to raise enough cash to cover another year's cash burn.
Since it has a market capitalisation of US$25m, Acurx Pharmaceuticals' US$7.2m in cash burn equates to about 29% of its market value. That's fairly notable cash burn, so if the company had to sell shares to cover the cost of another year's operations, shareholders would suffer some costly dilution.
So, Should We Worry About Acurx Pharmaceuticals' Cash Burn?
On this analysis of Acurx Pharmaceuticals' cash burn, we think its cash runway was reassuring, while its cash burn relative to its market cap has us a bit worried. Even though we don't think it has a problem with its cash burn, the analysis we've done in this article does suggest that shareholders should give some careful thought to the potential cost of raising more money in the future. Separately, we looked at different risks affecting the company and spotted 6 warning signs for Acurx Pharmaceuticals (of which 2 can't be ignored!) you should know about.
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>>> Acurx Announces Presentation and Update of Its pol IIIC R&D Pipeline at the World Antimicrobial Resistance Scientific Congress
PR Newswire
September 12, 2023
https://finance.yahoo.com/news/acurx-announces-presentation-pol-iiic-110100399.html
Ibezapolstat is currently enrolling in a Phase 2b trial for C. difficile infection in U.S. centers across the country and nearing its goal to reach a targeted 36 patients at which point an Interim Analysis of the unblinded primary clinical endpoint and safety data will be reviewed by an Independent Data Monitoring Committee
Ibezapolstat has received FDA QIDP and Fast-Track Designation
Also presented was an update on the Company's pre-clinical antibiotic program in Lead Optimization stage for systemic gram-positive bacterial infections, including Acute Bacterial Skin and Skin Structure Infections caused by MRSA
The company's preclinical pipeline also targets systemic infections caused by other gram-positive bacteria such as VRE and DRSP which are expected to be QIDP and Fast-Track eligible as product candidates advance in development
STATEN ISLAND, N.Y., Sept. 12, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced that a presentation was given by Acurx Executive Chairman, Robert J. DeLuccia, at the World Antimicrobial Resistance Scientific Congress on September 7, 2023. In his presentation at the Innovation Showcase session, he highlighted that the Company anticipates completing enrollment of the 36 patients required for an interim review of the Phase 2b data by the Independent Data Monitoring Committee (IDMC) in the coming months.
Mr. DeLuccia also presented an update on the Company's preclinical GPSS™ (Gram Positive Selective Spectrum) program for systemic oral and IV treatment of other gram-positive infections including MRSA, VRE and DRSP. Mr. DeLuccia summarized the progress stating that "Our potential lead compound meets Theurezbacher's criteria for antibiotic innovation in that it is a new chemical class, has novel mechanism and bacterial target, and has not shown cross-resistance in early in vitro microbiology studies." He further stated: "Having established clinical validation of the pol IIIC bacterial target in a Ph2a proof-of-principal trial showing 100% cure of C. difficile Infection, with no recurrence after 30 days' follow up, we have made substantial progress toward lead compound selection of our gram-positive IV and oral compounds. We've made significant improvements in invitro and invivo safety and have demonstrated oral and IV efficacy in a number of mouse infection models. Our current focus is to prioritize the oral form for acute bacterial skin and skin structure staph infections, including MRSA, to speed lead product selection and advancement to the clinic."
The presentation is available on the Company's website www.acurxpharma.com.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
The Company currently is enrolling patients in a Ph2b clinical trial of ibezapolstat to treat patients with C. difficile infection (CDI). The Company successfully completed Phase 1 and Phase 2a clinical trials of ibezapolstat. The Phase 2a trial demonstrated 100% clinical cure and 100% sustained clinical cure in patients with CDI, along with beneficial microbiome changes during treatment including overgrowth of Actinobacteria and Firmicutes phylum species while on therapy and new findings which demonstrate potentially beneficial effects on bile acid metabolism. The Ph2b clinical trial is designed to enroll 64 patients and is a randomized (1:1), non-inferiority, double-blind trial of oral ibezapolstat compared to oral vancomycin, a standard of care to treat CDI.
The FDA has accepted the Company's plan to have an Independent Data Monitoring Committee (IDMC) conduct an interim review of clinical outcome from the ongoing Ph2b clinical trial of patients with C. difficile Infection (CDI). The interim review will be conducted upon reaching enrollment of 36 patients in total. FDA's acceptance was based on the Company's filing of a protocol amendment to its Investigational New Drug Application (IND) with FDA in January 2023. The Company's filing and intention for the IDMC to conduct an interim review of data was based on the observed blinded data to date from the ongoing Ph2b clinical trial at that time. Upon conducting the interim review, the IDMC will determine and recommend to the Company whether the most appropriate course of action is to terminate the Ph2b clinical trial early due to success, as the Company had done with the Ph2a clinical trial, or to continue patient enrollment. The Company intends to report available data promptly after the IDMC conducts this interim review. The IDMC initial organizational meeting was conducted in March 2023 and it has completed all organizational matters required to ensure readiness for data review.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About the World Antimicrobial Resistance Congress
Since 2015, the World Antimicrobial Resistance Congress has attracted top thought leaders, hospitals, companies, and policymakers as the annual, go-to event in the Antimicrobial Resistance (AMR) space. It has grown into the most impactful event in advancing solutions to combat current and future pressing global health crises. Diagnostic developers, antibiotic biotechs & pharmaceutical companies, stewardship technologies, access firms, and many more, rely on our event for business development opportunities, networking and showcasing of new products and solutions. Over 1,300 attendees were expected to attend with over 200 speakers presenting over the two-day conference held in Philadelphia, PA on September 7-8, 2023.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care-associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported. (CID, 2022)
About the Ibezapolstat Phase 2 Clinical Trial
The multicenter, open-label single-arm segment of this study (Phase 2a) is to be followed by a double- blind, randomized, active-controlled segment (Phase 2b) which, together, comprise the Phase 2 clinical trial. The Phase 2 clinical trial is designed to evaluate ibezapolstat in the treatment of CDI. Phase 2a of this trial is completed and was an open- label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment, the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study. Based on the recommendation of Acurx's Scientific Advisory Board (SAB) and Trial Oversight Committee, we terminated enrollment in Phase 2a early and are now advancing to Phase 2b. The SAB unanimously supported the early termination of the Phase 2a trial after 10 patients were enrolled in the trial instead of 20 patients as originally planned. The early termination was based on the evidence of meeting the primary and secondary endpoints of eliminating the infection (100%), with no recurrences of infection (100%), and with an acceptable adverse event profile. In the Phase 2b, approximately 64 additional patients with CDI will be enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments will be identical in appearance, dosing times, and number of capsules administered to maintain the blind. This Phase 2 clinical trial also will evaluate pharmacokinetics (PK) and microbiome changes and continue to test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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>>> Acurx Pharmaceuticals Announces Successful Completion and Early Discontinuation of the Ibezapolstat Phase 2b Trial for Treatment of C. difficile Infection
PR Newswire
October 2, 2023
https://finance.yahoo.com/news/acurx-pharmaceuticals-announces-successful-completion-110100751.html
Based on observed aggregate blinded data the Company has determined that both treatments, ibezapolstat and the control antibiotic vancomycin, have performed as expected
High rates of Clinical Cure were observed without any emerging safety concerns
Data will be analyzed and topline efficacy results will be reported as soon as possible
This successful milestone will allow advancement of this first-in-class, FDA QIDP/Fast Track-designated antibiotic candidate to Phase 3 clinical trials more expeditiously
STATEN ISLAND, N.Y., Oct. 2, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today that the Company has discontinued the Phase 2b clinical trial of its lead antibiotic candidate, ibezapolstat, for the treatment of patients with Clostridioides difficile infection (CDI) due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19. The Company has determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns.
Accordingly, the Independent Data Monitoring Committee will not be required to perform an interim analysis of this Phase 2b trial data as originally planned and the Company has discontinued the trial. Acurx will analyze the data and report topline efficacy results promptly. The Company anticipates that this decision will allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "Considering the totality and weight of evidence of our preclinical, Phase 1 and Phase 2a clinical results and now with the observed aggregate blinded data, we determined it was in the best interests of the Company and its shareholders to discontinue the Phase 2b clinical trial early and prepare for Phase 3 clinical trials. Mr. DeLuccia stated further, "We look forward to compiling, analyzing the data and reporting topline results for the study's primary clinical endpoint and safety aspects as soon as possible". He further stated: "We thank the clinical trial investigators and patients across the country who participated in this study allowing advancement of this promising new antibiotic into late-stage clinical trials for this serious and life-threating infection which is classified by FDA and CDC as an urgent priority for which new classes of antibiotics are needed."
David P. Luci, the Company's President and Chief Executive Officer, stated: "We also look forward to reporting the full ibezapolstat data which will include the most extensive data for any antibiotic on sustained clinical cure to date in patients with CDI, as well as a comparison of the effect on the microbiome between oral ibezapolstat and oral vancomycin. We believe that, if approved by FDA for marketing, these attributes will support the use of ibezapolstat for front-line treatment of CDI."
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. In the now discontinued Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. This Phase 2 clinical trial will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long- term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme, and its R&D pipeline includes early-stage antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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>>> Being vegetarian may be partly determined by your genes
New Scientist
by Clare Wilson
https://www.msn.com/en-us/health/other/being-vegetarian-may-be-partly-determined-by-your-genes/ar-AA1hHHA2?OCID=ansmsnnews11
People’s likelihood of being vegetarian appears to be influenced by several genetic variants, and two of the three most important genes found so far seem to be involved in fat metabolism.
This hints that some people find it easier to give up meat because they naturally produce certain fat molecules, says Nabeel Yaseen at Northwestern University in Chicago. “Maybe there’s some fat that’s essential for some people to have in their diet but not for others,” he says.
About 5 per cent of people in the UK and US avoid all meat and fish. But surveys indicate that some people who say they are vegetarian still eat meat sometimes. That suggests that some people would like to be vegetarian but find it too hard, says Yaseen.
Genetic factors are known to influence other aspects of diet, such as whether people like coffee or alcohol. To see if genes also affect vegetarianism, Yaseen and his team turned to the UK Biobank, a large study where people filled in lifestyle and medical surveys and had their DNA sequenced. They analysed about 5300 people who said they were strict vegetarians and another 330,000 people who were meat eaters.
Three gene variants were more common in vegetarians. Two, called NPC1 and RMC1, are involved in the transport and metabolism of cholesterol and other fatty molecules called glycolipids. The third gene, called RIOK3, has various functions, including affecting the immune system.
It isn't known exactly how these genes could relate to vegetarianism. But one of the chief differences between animal-based foods and plant-based ones is the chemical make-up of their fats or oils, collectively known as lipids. Yaseen and his colleagues speculate that some people may function better on a vegetarian diet because they are more able to synthesise certain lipid molecules that are present in meat.
People who try vegetarianism but give up may be doing so because the body becomes deficient in the postulated essential lipids, says Yaseen. “They decide that this diet is not for them or gradually creep back into an omnivore diet. Some people might think they just don't have the willpower.”
Yaseen says, however, that another possibility is that the apparently vegetarianism-promoting gene variants affect people’s taste. “A lot of information about genes is yet to be known,” he says.
Albert Koulman at the University of Cambridge says most research into how food nutrients influence satiety and food choices has focused on proteins rather than fats. “We don’t know enough about [this idea] to either accept or dismiss it,” he says.
Richard McIlwain at the UK Vegetarian Society says the number of vegetarians has been rising in recent years, almost doubling in the UK between 2012 and 2019. “That would seem to suggest something other than underlying genetic factors are at play,” he says.
“People go vegetarian because, more and more, they are concerned about climate, about animal welfare or about their health. Psychological factors, such as tradition, education and awareness of animal suffering in food production, and ‘taste preferences’ are far more important determinants of vegetarianism than any physiological factors,” says McIlwain.
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CRDF reports 2nd quarter results. Much expanded relationship with PFE. Stock up 22% in AH.
- Advance to first-line RAS-mutated mCRC follows the strong signal from new clinical and preclinical data, and agreement with FDA -
- First-line mCRC represents substantial increase in patient impact and market opportunity over second-line -
- Pfizer Ignite will be responsible for the clinical execution of new first-line mCRC trial with interim topline data expected in mid-2024 -
- Cash position on June 30, 2023 was $89.4 million; sufficient to fund operations into 2025 and through interim topline results from mCRC trial -
- Company will hold a conference call today at 5:00 p.m. ET/2:00 p.m. PT -
SAN DIEGO, Aug. 7, 2023 /PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers, today announced plans to advance the company's lead program to the first-line setting of metastatic colorectal cancer (mCRC) and conduct its new CRDF-004 trial with study execution support from Pfizer Ignite, a new end-to-end service for biotech companies.
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SoC) therapeutics in clinical programs targeting indications such as KRAS/NRAS-mutated metastatic colorectal cancer (mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC), as well as in investigator-initiated trials in triple negative breast cancer (PRNewsfoto/Cardiff Oncology, Inc.)
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SoC) therapeutics in clinical programs targeting indications such as KRAS/NRAS-mutated metastatic colorectal cancer (mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC), as well as in investigator-initiated trials in triple negative breast cancer (PRNewsfoto/Cardiff Oncology, Inc.)More
"Our advance to the first-line mCRC setting is the result of a comprehensive data-driven review coupled with the agreement and support of the FDA. Ultimately, this decision moves Cardiff Oncology into a stronger position to realize the promise of onvansertib for the benefit of patients and all of our stakeholders," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We are delighted to expand our relationship with Pfizer and conduct this new first-line trial beginning this fall through Pfizer Ignite, leveraging its clinical execution capabilities and expertise."
The company estimates that there are 48,000 new patients in the U.S. annually in the first-line RAS-mutated mCRC setting for whom there are no ongoing clinical trials and no new treatments approved in the past 20 years.
Dr. Erlander continued: "Key to today's decision has been our discovery of a novel mechanism of action by which onvansertib inhibits angiogenesis by turning off a 'survival switch' for tumorigenesis. This has helped us understand onvansertib's interaction with bevacizumab, and the compelling clinical results we observed in our Phase 1b/2 second-line KRAS-mutated mCRC trial."
The clinical activities of the company's new CRDF-004 trial in first-line RAS-mutated mCRC will be conducted with support from Pfizer Ignite. This expands the relationship established in November 2021 when Pfizer made an equity investment in Cardiff Oncology and nominated Adam Schayowitz, Ph.D., Vice President & Medicine Team Group Lead for Breast Cancer, Colorectal Cancer and Melanoma, Pfizer Global Product Development as a Scientific Advisory Board member.
Pfizer Ignite is a new end-to-end service for biotech companies with high potential science that leverages Pfizer Inc.'s significant R&D capabilities, scale and expertise to accelerate the development of breakthrough therapies.
Cardiff Oncology will maintain full economic ownership and control of onvansertib.
"We believe onvansertib, by inhibiting PLK1, has the potential to play a meaningful role in the treatment of several types of cancer, including the lead program in RAS-mutated mCRC," said Dr. Schayowitz. "We believe that by combining Pfizer's clinical development capabilities and expertise, with onvansertib's promising novel clinical findings, we have an opportunity to accelerate the advancement of this program for the benefit of the many patients in the RAS-mutated mCRC setting."
Cardiff Oncology's new lead program in first-line RAS-mutated mCRC will consist of two trials that will be conducted sequentially. The first trial will be CRDF-004, a Phase 2 randomized trial generating preliminary safety and efficacy data and evaluating two different doses of onvansertib to confirm an optimal dose. Onvansertib will be added to standard-of-care consisting of FOLFIRI plus bevacizumab, or FOLFOX plus bevacizumab. A total of 90 patients will be randomized in a 1:1:1 ratio to either 20mg of onvansertib plus standard-of-care, 30mg of onvansertib plus standard-of-care, or standard-of-care alone. Interim topline results from this trial are expected in mid-2024.
Contingent upon the results of CRDF-004, Cardiff Oncology will initiate a Phase 3, randomized trial with registrational intent. The FDA has agreed that a seamless trial with objective response rate (ORR) at an interim point is an acceptable endpoint to pursue accelerated approval, with progression-free survival (PFS) and trend in overall survival being the endpoints for full approval.
"The stand-out results from our Phase 1b/2 second-line mCRC trial of onvansertib were observed in a well-defined subset of patients, namely those who had not previously been treated with bevacizumab in the first-line setting," said Fairooz Kabbinavar, MD, Chief Medical Officer of Cardiff Oncology. "Bev naïve patients in our Phase 1b/2 trial who received FOLFIRI, bevacizumab and onvansertib had a remarkable 73% ORR and 15-month mPFS, comparing favorably against historical controls that report an ORR of approximately 25% with a 7 to 8-month mPFS. Such high levels of efficacy have not been previously observed in 2nd line mCRC. The clinical and preclinical data we are reporting today confirm our initial finding, and based on highly encouraging interactions with the FDA and Pfizer, we are moving into first-line RAS-mutated mCRC where we believe enrollment should occur more quickly given the significantly larger number of first-line patients versus second-line."
Consistent with the strategic decision to focus on first-line RAS-mutated mCRC, Cardiff Oncology will discontinue enrollment in its ONSEMBLE second-line trial to focus resources on its new lead first-line program. This decision is driven by the fact that both trials essentially test the same clinical hypothesis, the importance of deploying the Company's capital efficiently, and the FDA's suggestion that Cardiff Oncology consider focusing on the first-line RAS-mutated mCRC setting.
All other Cardiff Oncology programs remain unaffected by this decision.
Conference Call and Webcast
Cardiff Oncology will host a corresponding conference call and live webcast at 5:00 p.m. ET/2:00 p.m. PT on August 7, 2023. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Investors" section of the company's website at www.cardiffoncology.com. A webcast replay will be available in the investor relations section on the company's website for 30 days following the completion of the call.
About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers. The company's lead asset is onvansertib, a PLK1 inhibitor being evaluated in combination with standard-of-care (SoC) therapeutics in clinical programs targeting indications such as RAS-mutated metastatic colorectal cancer (mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC), as well as in investigator-initiated trials in triple negative breast cancer (TNBC) and small cell lung cancer (SCLC). These programs and the company's broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SoC alone. For more information, please visit https://www.cardiffoncology.com.
Bladerunner
>>> Vistagen Therapeutics, Inc. (VTGN), a late clinical-stage biopharmaceutical company, primarily focus to transform the treatment landscape for individuals living with anxiety, depression, and other central nervous system (CNS) disorders. The company's pipeline includes six clinical stage product candidates, including five investigational agents belonging to drugs known as pherines. Its product pipeline comprises PH94B, a fasedienol nasal spray, which is in Phase III development for the treatment of social anxiety disorder; and PH10, a Ituvone nasal spray which is in Phase II development for the treatment of major depressive disorder. In addition, the company is also developing PH15, an early-stage investigational synthetic neuroactive steroid for the treatment of cognition improvement; PH80, an odorless and tasteless synthetic investigational pherine for the treatment of menopausal hot flashes and migraine; PH284, an early-stage investigational synthetic neuroactive steroid for the treatment of wasting syndrome Cachexia; and AV-101, an oral nmdr glycine site antagonist for depression and neurological disorders. Further, it has a license and collaboration agreement with EverInsight Therapeutics Inc. to develop and commercialize to address ophthalmologic and CNS disorders. The company was founded in 1998 and is headquartered in South San Francisco, California. <<<
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Blade, Instead of Ozempic for weight loss, you should check out cardiologist Dr. Steve Gundry (link below). Using his approach, I lost over 50 lbs (from 260 down to 205), and have easily kept it off, just by changing the types of foods consumed and by shortening the 'eating window' down to 8 hours/day (which replicates the natural eating cycle).
Gundry explains why most Americans are 'metabolically inflexible', and literally cannot burn fat at the mitochondrial level. He has numerous best selling books dealing with the various aspects, but following the info in his videos is sufficient to get the basic idea. It's a variation on the Mediterranean diet, but you need to avoid most grains (wheat, corn, soy, etc) since they contain 'lectins' (which cause leaky gut), and avoid processed foods, junk food, etc.
The ancient grains like sorghum and millet are fine, and beans are good but must be pressure cooked. Also lean meats and lots of organic vegetables. On the vegetable side, there are some to be avoided due to their lectin content, but most are fine. Peanuts and cashew are to be avoided (extremely high in lectins), but true nuts like pistachios and walnuts are great. Fruit intake is limited to in season (late summer, fall), although fruits like kiwis and avocados are good to eat all year.
Anyway, check out Gundry. Not only did I easily lose 50 lbs (less than 1 year), but my high blood pressure returned to normal, and autoimmune problems (primarily related to leaky gut) disappeared. Most of Gundry's diabetes and autoimmune patients (thousands) have been able to go off their meds, as the source of the immune system overactivity (leaky gut) is resolved.
A big key in Gundry's approach is reversing 'leaky gut' (intestinal hyperpermeability) and rebuilding the person's intestinal microbiome, which is extremely critical for good health.. Between over usage of antibiotics in medicine, and glyphosate herbicide residues on wheat, corn, the average American's gut microbiome has been absolutely devastated. Glyphosate / Roundup kills the intestinal flora by blocking the shikimate pathway, which is the same pathway associated with its weed killing ability. Glyphosate was originally patented by Monsanto as an antibiotic.
Gundry also has a lot to say about heart disease and cancer. Check him out -
>>> Moolec Science Presents 'Piggy Sooy', a Soybean Platform That Can Produce Significantly High Amounts of Pork Proteins
Accesswire
Moolec Science SA
June 26, 2023
https://finance.yahoo.com/news/moolec-science-presents-piggy-sooy-123000813.html
LUXEMBOURG / ACCESSWIRE / June 26, 2023 / Moolec Science SA ((NASDAQ:MLEC) "Company"; "Moolec"), a science-based food ingredient company focused on producing animal proteins in plants through Molecular Farming technology, announced today an outstanding achievement in its Meat Replacements Program for the Soybean platform, as its new "Piggy Sooy" produced a significantly high amount of pork protein.
Piggy Sooy
Piggy Sooy
The animal protein reached a high expression level up to 26.6% of total soluble protein in soy seeds, 4x higher than initially projected by the Company. The result can be directly observed due to the pink color of Moolec's soybeans, the same color as the pig (access the picture by clicking here). After this achievement, the Company's soybean platform was renamed "Piggy Sooy".
The breakthrough accomplishment has led Moolec to file a new patent utilizing a novel approach aiming to provide the Company with a frictionless regulatory pathway going forward.
Moolec's CEO & Co-Founder Gastón Paladini said: "Piggy Sooy represents tangible and visual proof that Moolec's technology has the capacity to achieve significant yields in plants to produce meat proteins. With this groundbreaking achievement, Moolec consolidates its position as a category creator and a pioneer in Molecular Farming for the food industry. Our plant biology team is writing the history of science in food, I couldn't be prouder of them."
This scientific milestone consolidates the Molecular Farming path as one of the most valuable alternative technologies to produce animal proteins, given that plants can function as animal protein factories in a more efficient manner than initially expected. This enhanced efficiency of plants has the potential to improve the economics of the Company's business model.
Moolec Science is producing several meat proteins in plants as functional ingredients to improve the taste, appearance, texture, and nutrition of meat alternatives. Due to its enhanced functionality and final application, the Company also highlighted that these food ingredients could also be potentially commercialized within the ~$600 billion traditional processing meat industry.
Amit Dhingra, Ph.D., Chief Science Officer of Moolec said: "This achievement opens up a precedent for the entire scientific community that is looking to achieve high levels of protein expression in seeds via Molecular Farming." He further emphasized: "Moolec has developed a unique, successful, and patentable platform for the expression of highly valuable proteins in the seeds of economically important crops such as soybeans. This platform has the potential to be used across a wide variety of proteins of interest for a broad range of industries, such as the pharma, cosmetic, diagnostic reagents, and other food industries."
About Moolec Science SA
Moolec is a science-based food ingredient company focused on producing animal proteins in plants through Molecular Farming, a disruptive technology in the alternative protein landscape. Its purpose is to upgrade the taste, nutrition, and affordability of alternative protein products while building a more sustainable and equitable food system. The Company's technological approach aims to have the cost structure of plant-based solutions with the organoleptic properties and functionality of animal-based ones. Moolec's technology has been under development for more than a decade and is known for pioneering the production of a bovine protein in a crop for the food industry. The Company's product portfolio and pipeline leverages the agronomic efficiency of broadly used target crops, like safflower, soybean, and pea. Moolec has a growing international patent portfolio (24, both granted and pending) for its Molecular Farming technology. The Company is run by a diverse team of Ph.Ds and Food Insiders, and operates in the United States, Europe, and South America. For more information, visit moolecscience.com.
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OCGN getting a nudge. Corp deck https://ocugen.gcs-web.com/static-files/e4bb4434-d94d-4d09-b119-ccfcb30af927
Candida Auris - >>> A deadly fungal infection is spreading in hospitals. Here's what to know.
by Jennifer Hassan and Fenit Nirappil
The Washington Post
March 21, 2023
https://www.yahoo.com/news/deadly-fungal-infection-spreading-hospitals-164045552.html
A deadly fungal infection is spreading at "an alarming rate" inside health facilities and long-term-care hospitals across the United States, the Centers for Disease Control and Prevention said Monday.
Here's what to know about the highly drug-resistant fungus - a strain of a kind of yeast known as Candida auris (or C. auris for short) that the CDC says "presents a serious global health threat."
While healthy people are not likely to contract the infection, those with lower immunity and people living in nursing homes are more likely to fall sick and be unable to fight the infection, and the outcome can be fatal.
What is Candida auris?
Candida is a family of yeasts that can be found on the skin and inside the body. Usually, the fungus lives in areas such as the mouth, throat, gut and vagina, without causing health problems. Common types of Candida include "Candida albicans," which causes the yeast infection thrush.
Sometimes, however, certain types of Candida can cause infection in older people and those battling other health issues.
C. auris was first discovered in the ear canal of a patient in Tokyo in 2009. It can enter the body during medical treatment, including operations or when urinary catheters, tubes or drips are inserted. It can also infect surgical wounds.
While the number of cases recorded by the CDC is only in the thousands, it is considered a serious global public health threat because it is drug resistant and has the potential to spread among the most medically vulnerable. It is also difficult to identify using standard laboratory methods, and it has caused outbreaks in health-care environments across the country.
What are the symptoms?
Candida auris can enter the bloodstream and spread throughout the body, causing invasive infections. Fever and chills that don't improve after antibiotic treatment for suspected bacterial infections are the most common symptoms of invasive candidiasis, the CDC notes.
The infection can aggravate various parts of the body, including the ears, heart, kidneys, eyes and brain.
How is the fungus transmitted?
The infection spreads easily from person to person - especially within hospital environments and among the medically vulnerable. It can also be spread through contact with infected surfaces and lingers on objects including hospital equipment such as bed rails, chairs and windowsills.
The infection can also be resistant to certain cleaning products, making it harder for the fungus to be eradicated from hospital wards.
People can also carry the infection without experiencing symptoms, unknowingly spreading the infection to other people who may be more at risk, such as people in long-term health-care facilities, including nursing home patients on ventilators, those with diabetes and cancer patients.
Those who take lots of antibiotics or antifungal medications appear to be at highest risk of infection, according to the CDC.
Between 30 percent and 60 percent of hospitalized people who develop bloodstream infections are estimated to die, according to CDC data. However, the CDC notes that many of these patients had other serious illnesses that increased their risk of death.
The CDC says more work is needed to understand how the infection spreads.
Which U.S. states has the fungus been identified in so far?
C. auris was diagnosed in a handful of patients in the United States in 2016, where clinicians on American soil had been warned by health officials to be on the lookout for the infection.
It has since been detected in more than 20 states, with the most cases recorded in Nevada, California, Florida New York, Illinois and Texas in the past 12 months, according to case counts provided to the CDC by local and state health departments.
Fungal infections from Candida auris tripled nationally from 476 in 2019 to 1,471 in 2021, the CDC said Monday.
Where else in the world have outbreaks been reported?
Since it was first reported in Asia in 2009, the fungus has been reported in a slew of countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Korea, Venezuela and Britain.
Transmission of the infection was facilitated by international travel, according to the CDC, though experts say that climate change may also be fueling the infection. The infection also worsened amid the coronavirus pandemic, which hospitalized more people around the world, overburdening health-care staff who were forced to reuse personal protective equipment.
Clinical cases of C. auris soared about 60 percent in 2020 compared to 2019, according to a 2022 report from the CDC that noted the global pandemic "likely intensified spread of C. auris and hindered detection of additional cases."
One leading theory suggests that Candida has evolved to survive in a warming world, while other theories suggest that widespread use of antifungal drugs along with heavy use of fungicide on crops may have sparked the emergence of the fungus.
How can the spread be prevented?
The CDC says that several infection control measures can help prevent C. auris, including adherence to hand hygiene and thoroughly cleaning hospital environments. Equipment that is shared among patients, such as blood pressure cuffs, temperature probes and ultrasound machines, should be thoroughly disinfected frequently.
Alcohol-based hand sanitizer, gowns and gloves should also be used to reduce the spread of infection inside health-care facilities.
According to the CDC, those who have the infection and their close contacts do not have to self-isolate and can participate in social activities as long as they maintain good hand hygiene.
How is the infection diagnosed and treated?
The infection is difficult to identify with standard laboratory methods because the yeast can be mistaken for other organisms, so specific technology is needed, the CDC says.
While the CDC says most C. auris infections are treatable with antifungal medications called echinocandins, some strains of the infection have developed a resistance to antifungal drugs, making it harder to treat patients, and cases of reinfection have also been recorded.
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>>> Researchers discover way to combat superfungi
The News Glory
06/07/2023
https://thenewsglory.com/researchers-discover-way-to-combat-superfungi/
Researchers discover way to combat superfungi
A study conducted at USP reveals that brilacidin, a new drug tested for illnesses ranging from bacterial skin infections to Covid-19, can kill resistant strains of fungi when combined with two classes of antifungals available on the market.
The new potential application of the medicine, now patented and described in the journal Nature Communications, was discovered by researchers from the Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP), in the interior of São Paulo, supported by FAPESP.
The problem of drug resistance is a challenge recognized by the WHO (World Health Organization), but the process of developing a new drug is very expensive and time-consuming.
“For this reason, we sought to identify the antifungal activity of chemical molecules that were already known, but which until then had not been studied in terms of their effects on controlling fungal growth. In this case, we started by exploring 1,400 chemical compounds until we arrived at this one”, says Thaila Fernanda dos Reis, postdoctoral fellow at FCFRP-USP and first author of the article.
Thanks to the use of different methods, the researchers concluded that the combination of brilacidin with two different antifungal drugs (caspofungin or voriconazole) has the ability to kill resistant strains of several species of fungus that cause infections in humans, such as Aspergillus fumigatus, the causative agent of invasive pulmonary aspergillosis.
Aspergillosis is a common infection in patients admitted to intensive care units (ICUs), which can lead to death in between 60% and 90% of individuals. It also affects patients with a certain degree of immune impairment, such as those undergoing cancer treatments.
In addition to combinations with antifungals for lung infections, brilacidin alone blocked the growth of the A. fumigatus and disease development in an animal model of keratitis, an infection that affects the cornea.
The eye disease affects 1 to 2 million people a year worldwide, especially in tropical countries with great agricultural activity. In the United States and other developed countries, the use of contact lenses contaminated with mold is the main risk factor.
Mechanism of action
Drug resistance occurs when the microorganism (fungus, bacteria or virus) finds a way to survive and continue to multiply even in the presence of the drug that should have stopped its growth.
Therefore, it is important to have drug options that act in different ways on the pathogen, in order to eradicate the infection even when the strain is resistant to some drug. However, while there are nine classes of antibacterials, there are only four classes of antifungals commercially available.
Caspofungin, for example, is an antifungal that has been available on the market for a long time. Its mechanism of action consists of inhibiting the synthesis of the cell wall, a structure that surrounds the plasma membrane and maintains the integrity of the fungal cell.
When in contact with the drug, however, not infrequently, the fungus activates a repair system, which bypasses the action of the drug and allows it to survive in its presence. Hence the potential of the combination of caspofungin and brilacidin. In tests, the presence of the new molecule disabled the repair system triggered by caspofungin.
“Caspofungin does not kill the fungus A. fumigatus, but hinders its multiplication. This is often enough for the host’s immune system to control the infection, but not always. That is why it is important to identify drugs capable of acting in synergy with One of the options would be to create a single drug that combined caspofungin and brilacidin simultaneously, so that they could act together”, summarizes Gustavo Henrique Goldman, a professor at FCFRP-USP who coordinated the study.
Superfungi
Another advantage of brilacidin is that the combination with caspofungin or voriconazole had action against different species of fungus.
In tests with animal models, in addition to A. fumigatus, the combination of brilacidin with caspofungin was effective in inhibiting other fungal species such as Candida albicans, Candida auris and Cryptococcus neoformans.
Called “superfungi” because of their high drug resistance, some of these strains have been blamed for serious nosocomial infections. Recently, they have become more common due to the large number of hospitalizations in ICUs due to the COVID-19 pandemic.
The synergistic action of brilacidin with voriconazole, in turn, was effective both against A. fumigatus and against Mucorales, a fungus that occurs mainly in India and Pakistan and causes serious deformations of the face.
For the effects to be proven in humans, however, clinical trials are needed. Together with the company that owns the brilacidin patent, the North American Innovation Pharmaceuticals Incorporated, the researchers are now looking for a Brazilian company that can license the medicine in the country and carry out the clinical tests, necessary to prove the effects in humans and, in case of successfully make the drug available on the market.
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>>> Axsome aims to give its balance sheet a boost
https://www.fool.com/investing/2023/06/28/as-the-bull-roars-shareholders-hate-how-these-2-co/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Shares of Axsome Therapeutics were down 9% early Wednesday morning. The biopharmaceutical company specializing in treatments for central nervous system disorders announced that it would sell shares of common stock.
Axsome's motivation is clear. As a biotech with a pipeline of candidate drugs, Axsome needs cash in order to run late-stage clinical trials on its most promising treatments, and the proceeds from the offering will go toward both existing and potential new clinical programs in the future. In addition, Axsome will need capital to expand its commercialization efforts for its already-approved Sunosi drug for sleep disorders and its antidepressant drug Auvelity.
The filed prospectus did not indicate a specific number of shares that Axsome intends to sell. However, the offering will fall under an existing shelf registration statement.
In the past couple of weeks, Axsome has told investors that it expects its top treatments to generate as much as $11.5 billion in revenue in the U.S. market at peak sales, which dramatically exceeds what most analysts following the stock had projected. Moreover, if Auvelity pans out as a possible treatment that could help Alzheimer's disease as well as those looking to quit smoking, then it could dramatically expand its addressable market and add to Axsome's overall success.
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>>> Has the Serotonin Hypothesis Been Debunked?
Not really. It never meant anything.
Psychology Today
Nassir Ghaemi M.D., M.P.H.
October 1, 2022 |
https://www.psychologytoday.com/us/blog/mood-swings/202210/has-the-serotonin-hypothesis-been-debunked#:~:text=The%20serotonin%20hypothesis%20of%20depression%2C%20popular%20from%20the%201990s%20until,was%20proven%20to%20begin%20with.
KEY POINTS
The serotonin hypothesis of depression never was a legitimate scientific hypothesis that could be proven or disproven.
It was meaningless in the sense of being too broad, and clearly false when defined more narrowly.
A recent review paper simply points out the absence of evidence for it, which was well-known for decades.
The serotonin hypothesis of depression, popular from the 1990s until now, is false, and has been known to be false for a long time, and never was proven to begin with. The norepinephrine hypothesis of depression, which preceded the serotonin hypothesis in the 1960s to the 1980s, also was false, and has been known to be false for a long time, and never was proven to begin with. The same holds for the dopamine hypothesis of schizophrenia, which began in the 1960s and 1970s, and more generally for the “chemical imbalance” metaphor for all mental illness.
All of these are major oversimplifications, which most scientists realize are major oversimplifications, but which the general public and many clinicians have assumed to be true. A recent review paper merely documents the absence of much if any scientific evidence for these oversimplified false hypotheses. So it’s not new scientifically at all. The first author of the review has been a major critic of psychiatric medications in general, especially serotonin reuptake inhibitors (SRIs), and thus the main purpose of the paper may be to seek to undermine the use of SRIs. It may indeed do so for the general public and those clinicians who have believed the false concepts of chemical imbalance and/or the serotonin hypothesis of depression. But for scientists and researchers, the use of SRIs is completely unrelated to these false metaphors. The use of SRIs should be based solely on the efficacy data shown for those agents in randomized clinical trials. Those data are indeed weak, and thus, I hold the view that SRIs should be used much less than they are, and for shorter durations, but this view has nothing to do with the already known false concepts of a serotonin theory of depression.
Another feature of the paper, which usually isn’t acknowledged, is that the absence of a relationship between measures of serotonin and “depression” also is expected and routine because that is the case with any biological marker of any kind in psychiatry in the past 40 years and any DSM-based diagnosis. By “depression” these studies usually mean DSM-defined “major depressive disorder” (MDD), and almost all studies for the last 40 years find that no biological marker correlates with most DSM diagnoses (with important exceptions in schizophrenia and bipolar illness). The problem is that DSM diagnoses are not biologically valid because they are not scientifically based; they are not based solely on scientific evidence but rather are social constructions of the American psychiatric profession. Hence they are not useful for biological research and almost always produce negative results, as in this paper. The NIMH leadership acknowledged this major problem in 2013 when the DSM-5 came out and since that time the NIMH policy has been to not use DSM diagnoses for biological research. So again this review is only documenting what is already known in general: Most DSM diagnoses, like MDD, do not correlate with any biological measure, like serotonin.
More generally: It is obvious that these false views are based on backward logic. Since SRIs improved depressive symptoms somewhat in clinical trials (though much less than people believe), it was assumed that depression had a basis in “low” serotonin. This would be like saying that since aspirin is a prostaglandin inhibitor, and it reduces fever, then fever is a prostaglandin disorder. In fact, prostaglandin effects is just one way to reduce fever, and it is only a last step to reducing fever. The real way to reduce fever is to stop the cause of fever earlier in the process, as with antibiotics for the bacteria that cause infections that produce fever.
Similarly with SRIs and serotonin. SRIs are only symptomatic drugs; they reduce symptoms of depression somewhat, just as aspirin reduces symptoms of fever. Their mechanism, increasing serotonin, may have nothing at all to do with the psychiatric diseases that cause depression, such as manic-depressive illness, just as the mechanism of aspirin has nothing to do with the infectious diseases that cause fever.
Also, the brain just doesn’t work that way. It’s not about “high” this or “low” that. There are many chemicals in the brain interacting with each other in a very complex manner, with negative and positive feedback loops, so that there is no sense at all to say that anything in the brain relevant to any illness has to do with simply having too much or too little of any chemical. Further, besides the chemicals often discussed, like serotonin, norepinephrine, and dopamine, there are hundreds of other proteins, called second messengers, that relay information inside neurons related to these chemicals. And those second messengers interact with each other in a myriad of ways. If SRIs partially influence depression by their effects on serotonin – even if we accept this simple statement – those effects are then transmitted by hundreds of other proteins and second messengers in ways that are far too complex to describe.
So how should clinicians explain depression to their patients? This is what I do and recommend:
“Depression is not a disease; it is a set of symptoms, like fever, chills, and night sweats. I would be a bad doctor if I just gave you anti-fever pills and anti-chill pills and anti-night sweat pills, instead of treating the infection that caused all those symptoms. Similarly, antidepressants like SRIs improve the symptoms of depression somewhat, but don’t get at the cause. Just like aspirin and Tylenol can improve the symptoms of fever somewhat, but don’t get at the cause. We might use antidepressants short-term for symptom benefit, but we should also try to find the disease that is causing your depression, such as manic-depressive illness.”
THE BASICS
What Is Depression?
Further, I could say: “Depression is not a ‘chemical imbalance’ because there is no ‘chemical balance.’ These are false metaphors. The brain is complex and many chemicals are active in many different directions in the brain. Your depression may be biological disease, in which chemicals are functioning abnormally, but it’s not about just having too much or too little of anything. And it’s not about getting everything into some ‘balance.’ It’s about treating the disease itself.”
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(also - the 'placebo effect' can be a very significant factor with antidepressant meds. The placebo effect is sometimes in the 50% range in clinical trials)
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>>> Study drugs make people worse at problem solving, not better
The Economist
June 20, 2023
https://finance.yahoo.com/news/study-drugs-people-worse-problem-171714158.html
FOR MORE THAN six months Americans have been struggling to get their hands on medications like dextroamphetamine (better known as Adderall) and methylphenidate (Ritalin). Officially, these stimulant drugs—alongside another, Modafinil (Provigil)—are used to treat attention-deficit hyperactivity disorder (ADHD).
Unofficially, the drugs are also popular with devotees of “nootropics”—chemicals that supposedly boost brainpower. Students and workers in industries from tech to finance take the medications in the hope they will improve concentration and ability to get things done. But a new paper suggests that this may be ill-advised. The drugs seem to make people slightly worse at solving problems, not better.
In a paper published on June 14th in Science Advances, a group of researchers led by Peter Bossaerts, an economist at the University of Cambridge, tested how Adderall, Provigil and Ritalin affected 40 healthy people’s ability to perform optimisation problems. They used the “knapsack task”, in which participants had to work out which items to put into a bag. The idea was to maximise the value of the items without exceeding the carrying weight of the sack. The researchers used several trials of varying difficulty, each with different weight limits and lists of items.
The participants visited the lab on four separate days. On each day they were given either a placebo pill or one of the drugs under study. The study was double-blind, meaning neither the participants taking the pills nor the experimenters handing them out knew which had been administered on which day. They found that participants achieved slightly worse end results on the task after taking a drug. The drugs did not impair people’s ability to find an optimal solution. Participants managed this in around half of the trials, whether they took the drugs or the placebo pills. But they did cause a small drop in the value of participants’ knapsacks across all trials, by making the non-optimal solutions worse.
Perhaps more striking was how drugs changed the way people attacked the task. After taking Adderall or Ritalin (but not Provigil) the participants spent far longer working on their knapsacks than they did when they had taken the placebo pill. (Participants were given four minutes to complete each trial but could submit an answer earlier if they thought they had found a good solution). When given Ritalin in particular, subjects were around 50% slower at completing trials. That was roughly equivalent to the delay expected from going from the easiest to the most difficult trial in the placebo session.
This extra time was spent moving items in and out of the knapsack, somewhat erratically. The authors assessed the productivity of each move by measuring how much it increased the value of a sack, and found that participants were about 9% less productive when they had taken one of the study drugs compared with a placebo pill. “It was like they were trying to solve a jigsaw puzzle by randomly throwing pieces in the air,” says Dr Bossaerts.
The authors argue that although the drugs made people more motivated and helped them put more effort into the task, this was more than cancelled out by the fact that the drugs decreased the quality of all that effort. In other words, although people tried harder, they became far less competent. Just how much the drugs hindered performance seemed to depend on how good a participant was without them. Star performers during the placebo session fell to the bottom of the pack when they had taken the drugs.
Popping stimulants is commonplace in industries like software and finance. One survey of 6,500 American college students reported that 14% had used the drugs for non-medical reasons. This latest study adds to a growing pile of evidence suggesting that such drugs do little to improve cognitive performance in people who do not need them. For tech bosses looking for efficient employees, and workers hoping to clock off at a reasonable hour, the stimulant shortage may be a good thing.
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>>> Aaron Rodgers talks about mental heath at a psychedelics conference
San Diego Union Tribune
by JESSE BEDAYN
6-21-23
https://www.msn.com/en-us/sports/nfl/aaron-rodgers-talks-about-mental-heath-at-a-psychedelics-conference/ar-AA1cPMMC
An eclectic crowd of thousands — podcasters, vendors, startups, seekers — swarmed a psychedelics conference in Denver this week to experience everything from a dimly lit hall packed with kaleidoscope art and a wide-ranging lineup of speakers from a former Republican governor to NFL star quarterback Aaron Rodgers.
The conference, put on by a psychedelic advocacy group, took place months after Colorado’s voters decided to join Oregon in decriminalizing psychedelic mushrooms. While it’s a sign of growing cultural acceptance for substances that proponents say may offer benefits for things like post-traumatic stress disorder and alcoholism, medical experts caution that more research is needed on the drugs’ efficacy and the extent of the risks of psychedelics, which can cause hallucinations.
Rodgers, who’ll soon debut with the New York Jets after years with the Green Bay Packers, spoke Wednesday night with podcaster Aubrey Marcus. Rodgers described taking ayahuasca with his teammates as “radically life-changing,” and claimed many other pro athletes have reached out to him.
“I found a deeper self love,” said Rodgers of his ayahuasca experience. “It unlocked that whole world of what I’m really here to do is to connect, to connect with those guys, and to make those bonds and to inspire people.”
The organization hosting the conference, the Multidisciplinary Association for Psychedelic Studies, is the largest U.S. advocacy group. It has strategized to reach the full political spectrum, said Nicolas Langlitz, a historian of science who’s researched the boom and bust of psychedelic movements.
“At the time when any topic gets politically polarized, ironically, these super-polarizing substances now get bipartisan support," Langlitz said. Still, he added, the conference is “purely designed to promote the hype."
“Any kind of overselling is not good for science because science should be accurate rather than pushing things," he said. “It’s a tradeoff. (The conference) generates interest, it generates ultimately more research, even though the research might be skewed toward positive results.”
Psychedelics are illegal at the federal level, though acceptance and interest in studying their potential benefits has grown. For example, some researchers believe psilocybin, the compound in psychedelic mushrooms, changes the way the brain organizes itself and can help users overcome things like depression and alcoholism.
The drugs themselves — and the interest in them — are not new. Mid-last century, Aldous Huxley, Timothy Leary and Ken Kesey helped spur the use of psychedelics during the counterculture movement, and optimism brimmed among some psychologists over the drugs’ potential.
But the Nixon administration criminalized psychedelics, pushing them underground.
“In both cases you have this upwelling of exuberance that may or may not be irrational,” said author Michael Pollan, who wrote a book on psychedelics and will be speaking at the conference. “But I think a big difference (now) is that the enthusiasm for the potential of psychedelics cuts across a much more representative slice of the population — it’s not about a counterculture."
Republican strongholds, including Utah and Missouri, have or are considering commissioning studies into the drugs, partly inspired by veterans’ stories. Former Texas Republican Gov. Rick Perry spoke Wednesday about helping get a bill passed in the Texas legislature in 2021 to fund a study of psilocybin for veterans, though he doesn't support recreational use. In Congress, similar veteran-focused proposals brought progressive Democratic Rep. Alexandria Ocasio-Cortez from New York and far-right Rep. Matt Gaetz from Florida into an unlikely alignment.
Public interest also appears to be growing. Just six years ago in Oakland, California, the Multidisciplinary Association for Psychedelic Studies held a conference with roughly 3,000 attendees and a smattering of lesser-known speakers and die-hard proponents.
This time, organizers estimate at least 10,000 attendees. Other famous speakers will include former NHL player Daniel Carcillo, who owns a company specializing in psychedelic therapies; Olympic silver-medal figure skater Sasha Cohen; rapper and actor Jaden Smith; comedians Reggie Watts and Eric Andre, top-10 podcaster Andrew Huberman; and Carl Hart, the chair of Columbia University's psychology department.
Recruiting that celebrity support for psychedelics is part of MAPS' public relations strategy, founder Rick Doblin said. When asked whether platforming a non-expert like Rodgers could mislead the public, Doblin demurred, adding it would be “dangerous” for anyone to claim that there are no risks to taking psychedelics.
Doblin said taking MDMA should happen “only under the direct supervision of a therapist, it's never a take-home medicine.” He also emphasized what many speakers echoed during the first day about psychedelics being paired with mental health professional: “The treatment is not the drug, it’s the therapy that the drug makes more effective."
That was a more tempered approach than his introductory speech, when, to an overflowing theater, Doblin espoused grandiose goals such as “net-zero” trauma by 2070 through the use of psychedelics.
The American Psychiatric Association has not endorsed the use of psychedelics in treatment, noting the Food and Drug Administration has yet to offer a final determination. The FDA did designate psilocybin as a “breakthrough therapy” in 2018, a label that’s designed to speed the development and review of drugs to treat a serious condition. MDMA, often called ecstasy, also has that designation for PTSD treatment.
Both Pollan and Langlitz believe further research is key — especially as the nation faces an unprecedented mental health crisis and people struggle to find adequate treatment. But, Langlitz said, it's important to let research shape the narrative.
“I would just try to keep my mind open to the possibility that in retrospect we will tell a very different story from the one that the protagonists of psychedelic therapies are currently predicting,” he said.
<<<
---
>>> Synthetic human embryos created in groundbreaking advance
Exclusive: Breakthrough could aid research into genetic disorders but raises serious ethical and legal issues
Analysis: advances leave legislators needing to catch up
The Guardian
Hannah Devlin
14 Jun 2023
https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in-groundbreaking-advance
Scientists have created synthetic human embryos using stem cells, in a groundbreaking advance that sidesteps the need for eggs or sperm.
Scientists say these model embryos, which resemble those in the earliest stages of human development, could provide a crucial window on the impact of genetic disorders and the biological causes of recurrent miscarriage.
However, the work also raises serious ethical and legal issues as the lab-grown entities fall outside current legislation in the UK and most other countries.
The structures do not have a beating heart or the beginnings of a brain, but include cells that would typically go on to form the placenta, yolk sac and the embryo itself.
Prof Magdalena Zernicka-Goetz, of the University of Cambridge and the California Institute of Technology, described the work in a plenary address on Wednesday at the International Society for Stem Cell Research’s annual meeting in Boston.
“We can create human embryo-like models by the reprogramming of [embryonic stem] cells,” she told the meeting.
There is no near-term prospect of the synthetic embryos being used clinically. It would be illegal to implant them into a patient’s womb, and it is not yet clear whether these structures have the potential to continue maturing beyond the earliest stages of development.
The motivation for the work is for scientists to understand the “black box” period of development that is so called because scientists are only allowed to cultivate embryos in the lab up to a legal limit of 14 days. They then pick up the course of development much further along by looking at pregnancy scans and embryos donated for research.
Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute in London, said: “The idea is that if you really model normal human embryonic development using stem cells, you can gain an awful lot of information about how we begin development, what can go wrong, without having to use early embryos for research.”
Previously, Zernicka-Goetz’s team and a rival group at the Weizmann Institute in Israel showed that stem cells from mice could be encouraged to self-assemble into early embryo-like structures with an intestinal tract, the beginnings of a brain and a beating heart. Since then, a race has been under way to translate this work into human models, and several teams have been able to replicate the very earliest stages of development.
The full details of the latest work, from the Cambridge-Caltech lab, are yet to be published in a journal paper. But, speaking at the conference, Zernicka-Goetz described cultivating the embryos to a stage just beyond the equivalent of 14 days of development for a natural embryo.
The model structures, each grown from a single embryonic stem cell, reached the beginning of a developmental milestone known as gastrulation, when the embryo transforms from being a continuous sheet of cells to forming distinct cell lines and setting up the basic axes of the body. At this stage, the embryo does not yet have a beating heart, gut or beginnings of a brain, but the model showed the presence of primordial cells that are the precursor cells of egg and sperm.
“Our human model is the first three-lineage human embryo model that specifies amnion and germ cells, precursor cells of egg and sperm,” Zernicka-Goetz told the Guardian before the talk. “It’s beautiful and created entirely from embryonic stem cells.”
The development highlights how rapidly the science in this field has outpaced the law, and scientists in the UK and elsewhere are already moving to draw up voluntary guidelines to govern work on synthetic embryos. “If the whole intention is that these models are very much like normal embryos, then in a way they should be treated the same,” Lovell-Badge said. “Currently in legislation they’re not. People are worried about this.”
There is also a significant unanswered question on whether these structures, in theory, have the potential to grow into a living creature. The synthetic embryos grown from mouse cells were reported to appear almost identical to natural embryos. But when they were implanted into the wombs of female mice, they did not develop into live animals. In April, researchers in China created synthetic embryos from monkey cells and implanted them into the wombs of adult monkeys, a few of which showed the initial signs of pregnancy but none of which continued to develop beyond a few days. Scientists say it is not clear whether the barrier to more advanced development is merely technical or has a more fundamental biological cause.
“That’s very difficult to answer. It’s going to be hard to tell whether there’s an intrinsic problem with them or whether it’s just technical,” Lovell-Badge said. This unknown potential made the need for stronger legislation pressing, he said.
<<<
---
OCGN 5 min volume. Holding cash shares.
Blade, Phenomenal move, and I see that analysts have price targets of $10 and $20, so could be lots more to go :o)
>>> Why Shares of Gracell Biotechnologies Jumped Tuesday
Motley Fool
By Jim Halley
Jun 13, 2023
https://www.fool.com/investing/2023/06/13/why-shares-of-gracell-biotechnologies-jumped-tuesd/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
KEY POINTS
Two analysts upgraded their ratings for Gracell Biotechnologies' stock.
Over the weekend, Gracell announced positive follow-up trial data regarding its lead therapy.
The clinical-stage biotech has no revenue and cash of $186 million, as of the first quarter.
Gracell climbed higher for a second consecutive day.
What happened
Shares of Gracell Biotechnologies (GRCL 28.06%) were up 21.5% Tuesday afternoon. The healthcare stock rose for the second consecutive day, boosted by an analyst's upgrade, as well as by positive trial news. The stock is up more than 156% so far this year.
So what
Gracell is a clinical-stage biotech company that makes cell therapies to treat cancers and autoimmune diseases. Over the weekend, the company announced positive long-term follow-up trial data regarding its lead therapy, GC012F, to treat patients with relapsed/refractory B-cell non-Hodgkin's lymphoma. The CAR-T therapy is a CD19 and B-cell maturation antigen.
In the study, all nine patients showed an overall response rate nine months after the therapy, with 77.8% having a complete response (CR) rate at three months and 66.7% having a CR at six months. The study comes on the heels of an announcement on June 3 that said GC012F did well in long-term follow-ups as a therapy to treat relapsed/refractory multiple myeloma.
In likely responses to the trial data, BTIG analyst Justin Zelin reiterated his buy rating on the stock with a price target of $20, and analyst Joseph Catanzaro from Piper Sandler maintained his buy rating on Gracell, with a price target of $10.
Now what
The company's pipeline has 12 programs, including six potential indications for GC012F. That the therapy has shown a strong safety profile, as well as long-term efficacy, is a big deal, but it is still in early-stage trials.
It's also worth noting that the small patient population size -- only nine participants -- means it may be difficult replicating GC012F's results in a larger relapsed/refractory B-cell non-Hodgkin's lymphoma patient group.
The company had, as of the first quarter, $186 million in cash, enough to probably finance operations into 2026.
<<<
---
GRCL sets new 52-week high at $6.37 obliterating its previous high of $5.94. Up almost 30%.
Bladerunner
GRCL up 25% today hitting it's 52-week high. Pulling back a bit as I write this.
Blade
Blade, Thanks. Looks great, and the stock has been flying :o) I see the company also has 3 proprietary platform technologies, so a good sign. Hopefully US-China relations don't deteriorate too far, but either way the ex-US market for GRCL should be plenty big.
Btw, looks like MRSN is also having a nice bounce, and JSPR is hanging in there after its big move :o)
---
GRCL present updated results at EHA. These rsults are outstanding, albeit in a small sample size.
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GlobeNewswire
Gracell Biotechnologies Presents Longer-Term Results for FasTCAR-T GC012F in B-Cell Non-Hodgkin’s Lymphoma at EHA2023, Highlighting 100% Overall Response Rate
Gracell Biotechnologies Inc.
Sat, June 10, 2023 at 7:30 AM PDT·7 min read
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Gracell Biotechnologies Inc.
Gracell Biotechnologies Inc.
Data on CD19/BCMA dual-targeting FasTCAR-T GC012F showed 100% overall response rate (ORR) and 66.7% 6-month complete response (CR) rate among treated patients, all with diffuse large B-cell lymphoma (DLBCL) subtype
Data on GC012F for treatment of relapsed/refractory multiple myeloma (RRMM) and donor-derived CAR-T GC007g for treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) have been presented as posters on June 9 at EHA2023
SAN DIEGO, Calif., and SUZHOU and SHANGHAI, China, June 10, 2023 (GLOBE NEWSWIRE) -- Gracell Biotechnologies Inc. ("Gracell" or the "Company", NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing innovative and highly efficacious cell therapies for the treatment of cancer and autoimmune disease, today presented longer-term follow-up data from a first-in-human study evaluating GC012F, a CD19 and B-cell maturation antigen (BCMA) dual-targeted autologous CAR-T therapeutic candidate, in patients with relapsed/refractory B-cell non-Hodgkin’s Lymphoma (r/r B-NHL) as an oral presentation (abstract #S234) at the European Hematology Association (EHA2023) Congress.
While CD19-directed CAR-T cell therapy has been demonstrated to be a valuable treatment option for r/r B-NHL, other studies have identified that 39% to 97% of clinical B-NHL samples express BCMA as well.1,2,3 To further improve safety and efficacy of NHL treatment, Gracell is exploring the clinical potential of GC012F, a CD19 and BCMA dual-targeting CAR-T cell therapy, for treatment of r/r B-NHL. GC012F is manufactured through a novel next-day FasTCAR process and demonstrated a younger phenotype of CAR-T cells and highly effective tumor killing activity in preclinical animal models.
In the single-arm, open label investigator-initiated trial (IIT), nine r/r B-NHL patients were enrolled and treated with GC012F, and completed at least three months of follow-up. Doses range between 3.7x104 to 3x105 CAR-T cells/kg. All nine patients are classified as relapsed/refractory DLBCL. All patients’ lymphoma samples expressed CD19, and samples from seven out of eight tested patients expressed BCMA.
As of the April 12, 2023 data cutoff date, with a median follow-up of 293 days (range: 131-546 days), patients treated with GC012F achieved a high response rate and outstanding durability of response:
100% (9/9) overall response rate (ORR) at 3 months among nine patients with r/r DLBCL;
77.8% (7/9) complete response (CR) rate at 3 months;
66.7% (6/9) CR rate at 6 months;
GC012F CAR-T cells were detectable in tumor biopsies from all tested patients, indicating the infiltration of CAR-T cells into the tumor lesions.
GC012F also continued to show a favorable safety profile:
Cytokine release syndrome (CRS) was mostly Grade 1 (56%; 5/9). Grade 3 CRS was observed in one patient (duration of 2 days) with quick recovery after standard of care treatment. No Grade 4/5 CRS events occurred;
No neurotoxicity or immune effector cell-associated toxicity (ICANS) of any grade were observed.
“One year after we reported initial data from the IIT evaluating FasTCAR-T GC012F in B-NHL at EHA2022, we are proud to be back at EHA presenting longer-term results from more patients as an oral presentation,” said Dr. Wendy Li, Chief Medical Officer of Gracell. “Durable responses, enhanced safety, and timely access to cell therapy remain significant unmet needs for NHL patients. With a 100% ORR at 3 months and CR rates of 78% at 3 months and 67% at 6 months, particularly among DLBCL patients, the updated data further support the clinical potential and wide applicability of GC012F, and the benefits of a CD19/BCMA dual-targeting approach combined with FasTCAR next-day manufacturing.”
Gracell is also evaluating GC012F in RRMM, newly-diagnosed multiple myeloma (NDMM), and systemic lupus erythematosus (SLE).
On June 9, Gracell also presented the following during poster sessions:
First results from a Phase 1 study of the donor-derived allogeneic CAR-T GC007g (abstract #P369), showing 100% ORR and a favorable safety profile for treatment of r/r B-ALL;
Updated results from the IIT evaluating GC012F for the treatment of RRMM (abstract #P869), which were also presented as an oral presentation at the 2023 ASCO Annual Meeting. The data demonstrated 100% minimal residual disease (MRD) negativity and 82.8% MRD negative stringent complete response (sCR) in a predominantly high-risk RRMM population.
Additional information about the presentations and the EHA2023 Hybrid Congress is available on the EHA website.
[1] Blood Cancer Journal (2020); 10:73.
[2] Blood (2017); 130:2755.
[3] Hum Gene Ther (2018); 29(5): 585.
About GC012F
GC012F is Gracell's FasTCAR-enabled BCMA/CD19 dual-targeting autologous CAR-T cell therapy, which aims to transform cancer and autoimmune disease treatment by driving fast, deep and durable responses with improved safety profile. GC102F is currently being evaluated in investigator-initiated trials in multiple hematological cancers as well as autoimmune disease, and has demonstrated a consistently strong efficacy and safety profile. In February 2023, Gracell announced regulatory clearance of Investigational New Drug applications in the United States and China to commence clinical trials evaluating GC012F for the treatment of relapsed/refractory multiple myeloma. Gracell has also initiated an investigator-initiated trial evaluating GC012F for the treatment of SLE.
About FasTCAR
Introduced in 2017, FasTCAR is Gracell's revolutionary next-day autologous CAR-T cell manufacturing platform. FasTCAR is designed to lead the next generation of therapy for cancer and autoimmune diseases, and improve outcomes for patients by enhancing effect, reducing costs, and enabling more patients to access critical CAR-T treatment. FasTCAR drastically shortens cell production from weeks to overnight, potentially reducing patient wait times and probability for their disease to progress. Furthermore, FasTCAR T-cells appear younger than traditional CAR-T cells, making them more proliferative and effective at killing cancer cells. In November 2022, FasTCAR was named the winner of the Biotech Innovation category of the 2022 Fierce Life Sciences Innovation Awards for its ability to address major industry obstacles.
About Gracell
Gracell Biotechnologies Inc. ("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CAR™ technology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors and autoimmune disease. For more information on Gracell, please visit www.gracellbio.com. Follow @GracellBio on LinkedIn.
Cautionary Noted Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.
CONTACT: Media contacts Marvin Tang marvin.tang@gracellbio.com Jessica Laub jessica.laub@westwicke.com Investor contacts Gracie Tong gracie.tong@gracellbio.com Stephanie Carrington stephanie.carrington@westwicke.com
Bladerunner
>>> Acurx Announces Ibezapolstat Scientific Poster and Update on its Pol IIIC Pipeline Presented at ECCMID 2023 Scientific Conference
PR Newswire
Apr 19, 2023
https://finance.yahoo.com/news/acurx-announces-ibezapolstat-scientific-poster-110100500.html
A scientific poster highlighting a novel pharmacologic property of oral ibezapolstat for C. difficile Infection likely related to its unique mechanism of action was presented at ECCMID 2023
An update on the Company's pre-clinical antibiotic program in Lead Optimization stage for systemic gram-positive bacterial infections was also presented
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., April 19, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced two presentations were given at the 33rd Annual European Congress of Clinical Microbiology and Infectious Disease (ECCMID) in Copenhagen. The scientific poster entitled "Novel Pharmacology and Susceptibility of Ibezapolstat Against C. difficile Isolates with Reduced Susceptibility to C. difficile-directed Antibiotics" was co-presented on April 17 by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy, and the Principal Investigator for microbiome aspects of our ibezapolstat clinical trial program, and by Dr. Eugénie Bassères, Research Scientist Faculty at the University of Houston. According to Dr. Garey: "Our work is based on the hypothesis that ibezapolstat's mechanism of action is not only bactericidal to C. difficile but also could inhibit some of its virulence mechanisms. C. difficile strains with reduced susceptibility to metronidazole, vancomycin, or fidaxomicin were susceptible to ibezapolstat, confirming its unique mechanism of action. To study anti-virulence effect, our group investigated an under-studied virulence property of C difficile, namely, flagellar movement of the organism. Using sub-MIC concentrations of ibezapolstat, we demonstrated decreased movement of C. difficile through a semi-solid agar in concert with reduced expression of the primary genes used to synthesize flagella. All of these positive and unexpected findings reflect the unique mode of action in inhibiting DNA pol IIIC and support the continued development of ibezapolstat to treat C. difficile infection."
Also, Acurx Executive Chairman, Robert J. DeLuccia, presented an update on April 15 on the Company's preclinical, systemic oral and IV program for treatment of other gram-positive infections caused by MRSA, VRE and DRSP at the "Pipeline Corner" featured session at ECCMID, organized by Dr. Ursula Theuretzbacher, a world-renowned microbiology expert involved in antibacterial drug research, discovery and development strategies and policies for clinical and public health needs. Mr. DeLuccia summarized the progress of the company's GPSS™ (Gram Positive Selective Spectrum) program stating: "Our potential lead compound meets Dr. Theurezbacher's criteria for innovation in that it is a new chemical class, has novel mechanism and bacterial target, and has not shown cross-resistance in early in vitro microbiology studies. He further stated: "Following clinical validation of the pol IIIC bacterial target in a Ph2a proof-of-principal trial showing 100% cure of C. difficile Infection, with no recurrence after 30 days' follow up, we have made substantial progress toward lead compound selection of our pan-active, gram-positive IV and oral compounds. We've made significant improvements in cytotoxicity, solubility and protein binding, in vitro and in vivo safety and have demonstrated oral and IV efficacy in a number of mouse infection models."
The poster and presentation are available on the Company's website www.acurxpharma.com.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
The Company currently is enrolling patients in a Ph2b clinical trial of ibezapolstat to treat patients with C. difficile infection (CDI). The Company successfully completed Phase 1 and Phase 2a clinical trials of ibezapolstat. The Phase 2a trial demonstrated 100% clinical cure and 100% sustained clinical cure in patients with CDI, along with beneficial microbiome changes during treatment including overgrowth of Actinobacteria and Firmicutes phylum species while on therapy and new findings which demonstrate potentially beneficial effects on bile acid metabolism. The Ph2b clinical trial is designed to enroll 64 patients and is a randomized (1:1), non-inferiority, double-blind trial of oral ibezapolstat compared to oral vancomycin, a standard of care to treat CDI.
The FDA has accepted the Company's plan to have an Independent Data Monitoring Committee (IDMC) conduct an interim review of clinical outcome from the ongoing Ph2b clinical trial of patients with C. difficile Infection (CDI). The interim review will be conducted upon reaching enrollment of 36 patients in total. FDA's acceptance was based on the Company's filing of a protocol amendment to its Investigational New Drug Application (IND) with FDA in January 2023. The Company's filing and intention for the IDMC to conduct an interim review of data was based on the observed blinded data to date from the ongoing Ph2b clinical trial at that time. Upon conducting the interim review, the IDMC will determine and recommend to the Company whether the most appropriate course of action is to terminate the Ph2b clinical trial early due to success, as the Company had done with the Ph2a clinical trial, or to continue patient enrollment. The Company intends to report available data promptly after the IDMC conducts this interim review. The IDMC initial organizational meeting was conducted in March 2023 and it has completed all organizational matters required to ensure readiness for data review.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About ECCMID
ECCMID (European Congress of Clinical Microbiology and Infectious Diseases) is recognized as the largest international forum for presentations and discussions of research in the fields of clinical microbiology and infection for experts from academia, the clinical setting and the industry. ESCMID's (European Society of Clinical Microbiology and Infectious Diseases) yearly congress attracts over 14,000 participants. ECCMID offers a wide range of sessions including: keynotes, symposia, poster sessions, educational workshops, meet-the-expert sessions and more. The society's executive power is vested in ESCMID in Executive Committee elected by the ESCMID members. The administrative ESCMID office is in Basel, Switzerland.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200;
doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported. (CID, 2022)
About the Ibezapolstat Phase 2 Clinical Trial
The multicenter, open-label single-arm segment of this study (Phase 2a) is to be followed by a double- blind, randomized, active-controlled segment (Phase 2b) which, together, comprise the Phase 2 clinical trial. The Phase 2 clinical trial is designed to evaluate ibezapolstat in the treatment of CDI. Phase 2a of this trial is completed and was an open- label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment, the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study. Based on the recommendation of Acurx's Scientific Advisory Board (SAB) and Trial Oversight Committee, we terminated enrollment in Phase 2a early and are now advancing to Phase 2b. The SAB unanimously supported the early termination of the Phase 2a trial after 10 patients were enrolled in the trial instead of 20 patients as originally planned. The early termination was based on the evidence of meeting the primary and secondary endpoints of eliminating the infection (100%), with no recurrences of infection (100%), and with an acceptable adverse event profile. In the upcoming Phase 2b, approximately 64 additional patients with CDI will be enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments will be identical in appearance, dosing times, and number of capsules administered to maintain the blind. This Phase 2 clinical trial also will evaluate pharmacokinetics (PK) and microbiome changes and continue to test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com.
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>>> Gracell Biotechnologies Reports First Quarter 2023 Unaudited Financial Results, and Provides Corporate Update
Gracell Biotechnologies Inc.
May 15, 2023
https://www.globenewswire.com/news-release/2023/05/15/2668595/0/en/Gracell-Biotechnologies-Reports-First-Quarter-2023-Unaudited-Financial-Results-and-Provides-Corporate-Update.html
Presenting longer-term follow-up data from investigator-initiated trial (IIT) evaluating BCMA/CD19 dual-targeting FasTCAR-T GC012F in relapsed/refractory multiple myeloma (RRMM) at 2023 ASCO and EHA
On track to commence a Phase 1b/2 clinical trial in U.S. and a Phase 1/2 clinical trial in China evaluating GC012F for the treatment of RRMM in the second quarter and third quarter of 2023, respectively
Launched the new IIT evaluating GC012F in systemic lupus erythematosus (SLE)
Presenting updated data from the ongoing IIT evaluating GC012F in relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) at 2023 ASCO and EHA2023
Presenting the Phase 1 clinical data of donor-derived allogeneic CAR-T GC007g in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) at EHA2023
Hosting KOL call on May 22 at 9:00 am ET to highlight unmet clinical need for RRMM in U.S.
Well-funded with cash runway to the end of 2024
Management to host conference call at 8:00 a.m. ET today
SAN DIEGO and SUZHOU, China and SHANGHAI, China, May 15, 2023 (GLOBE NEWSWIRE) -- Gracell Biotechnologies Inc. (NASDAQ: GRCL) (“Gracell” or the “Company”), a global clinical-stage biopharmaceutical company dedicated to discovering and developing highly efficacious and affordable cell therapies for the treatment of cancer and autoimmune diseases, today reported first quarter unaudited financial results for the period ended March 31, 2023, and provided corporate updates.
“We continue to focus our efforts on the advancement of our lead candidate GC012F, a FasTCAR-enabled autologous CAR-T therapy candidate dual-targeting B cell maturation antigen (BCMA) and CD19. We look forward to showcasing the updated clinical data of GC012F in two indications RRMM and r/r B-NHL at both 2023 ASCO and EHA2023, including in two oral presentations. We are on track to initiate the U.S. IND trial for GC012F in RRMM in the second quarter of 2023,” said Dr. William (Wei) Cao, founder, Chairman and CEO of Gracell. “We are also pleased to present the first clinical data from the Phase 1/2 clinical trial evaluating the donor-derived allogeneic CAR-T GC007g for the treatment of r/r B-ALL at EHA2023, demonstrating a 100% minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi) in a challenging set of patients.”
Dr. Cao continued, “We are excited to announce our strategic decision to pursue clinical development in systemic lupus erythematosus (SLE) for GC012F. We believe the FasTCAR-T GC012F is well positioned as an ideal candidate for a wide range of autoimmune indications, given its CD19/BCMA dual-targeting capability, consistently favorable safety profile demonstrated in the over 50 patients treated across three IITs, and the proprietary FasTCAR manufacturing technology. We recently commenced an IIT in China in refractory SLE patients and plan to file IND in U.S. and China subsequently.”
Pipeline Updates
FasTCAR Platform: Next-day manufacturing for autologous CAR-T cell therapy with enhanced cell fitness.
GC012F: FasTCAR-enabled autologous CAR-T therapy candidate dual-targeting BCMA and CD19, currently being evaluated for the treatment of RRMM, newly-diagnosed multiple myeloma (NDMM) and B-NHL.
Longer term follow-up from a multicenter IIT evaluating GC012F for the treatment of RRMM in heavily pretreated, mostly high-risk patients will be presented as oral presentation at 2023 American Society of Clinical Oncology Annual Meeting (2023 ASCO) and as poster presentation at European Hematology Association 2023 Congress (EHA2023).
Company-sponsored Phase 1b/2 clinical trial in U.S. (NCT05850234) evaluating GC012F in RRMM on track to initiate in the second quarter of 2023.
Company-sponsored Phase 1/2 clinical trial in China evaluating GC012F in RRMM expected to initiate in the third quarter of 2023.
Follow-up continued in the ongoing IIT evaluating GC012F in NDMM.
The first clinical data presented at ASH 2022 demonstrated that one single infusion of GC012F achieved a 100% overall response rate (ORR) and 100% minimal residual disease (MRD) negativity in 16 newly-diagnosed, high risk, transplant eligible patients across all dose levels. 75% of the treated patients did not experience any cytokine release syndrome.
On track to share updated clinical data in 2023.
Enrollment and follow-up continued in the IIT in China evaluating GC012F in r/r B-NHL.
Updated data to be presented as oral presentation at EHA2023 and as poster presentation at 2023 ASCO.
Initiated a new IIT evaluating GC012F in refractory SLE.
GC007g for the treatment of B-ALL: Allogeneic CD19-targeted CAR-T cell therapy, derived from human leukocyte antigen (HLA) matched donor, for the treatment of r/r B-ALL patients who failed transplant and may not be eligible for autologous CAR-T therapy.
Phase 1 data to be presented at EHA2023 in a poster presentation.
Between March 2021 and May 2022, nine r/r B-ALL patients were enrolled and treated in the Phase 1 portion of the registrational Phase 1/2 clinical trial at two different dose levels.
At day 28 after infusion, 100% patients achieved MRD- CR/CRi.
With a median follow-up duration of 445 days (range 218-649 days), seven of nine (78%) patients remained in CR/CRi.
Phase 2 portion of the registration Phase 1/2 clinical trial in China is ongoing.
TruUCAR Platform: Novel designs enabling “off-the-shelf” allogeneic CAR-T therapy.
GC502: CD19/CD7 dual-directed allogeneic CAR-T cell therapy candidate being studied in a Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured from T cells of non-HLA-matched healthy donors.
Data from an IIT evaluating GC502 in r/r B-ALL patients were presented at EHA2022. Three of four patients achieved MRD- CR/CRi at day 28 post-infusion.
SMART CARTTM Technology Module: With unique construct to take advantage of the suppressive tumor microenvironment (TME) and effectively combat solid tumors, SMART CARTTM is designed to enhance CAR-T cell proliferation and duration of killing, and to resist exhaustion with improved persistence of CAR-T cells.
On track to commence a China IIT for GC506 in Claudin18.2-positive solid tumors in the second quarter of 2023.
Financial Results for the First Quarter Ended March 31, 2023
As of March 31, 2023, the Company had RMB1,277.3 million (US$186.0 million) in cash and cash equivalents and short-term investments. In addition, the Company had short-term borrowings and current portion of long-term borrowings of RMB122.4 million (US$17.8 million) and long-term borrowings of RMB41.7 million (US$6.1 million).
Net loss attributable to ordinary shareholders for the three months ended March 31, 2023 was RMB151.7 million (US$22.1 million), compared to RMB158.6 million for the corresponding prior year period.
Research and Development Expenses
Research and development expenses for the three months ended March 31, 2023 were RMB137.5 million (US$20.0 million), compared to RMB121.8 million in the corresponding prior year period. The increase was primarily due to the increased spending on research, development, and clinical trials, including license expenses with Seagen Inc.
Administrative Expenses
Administrative expenses for the three months ended March 31, 2023 were RMB29.1 million (US$4.2 million), compared to RMB37.9 million for the corresponding prior year period. The decrease was primarily driven by a decrease in professional service as well as a decrease in share-based compensation expenses.
Interest income for the three months ended March 31, 2023 was RMB14.6 million (US$2.1 million), compared to RMB2.5 million for the corresponding prior year period. Interest expense for the three months ended March 31, 2023 was RMB1.7 million (US$0.2 million), compared to RMB1.4 million for the corresponding prior year period.
As of March 31, 2023, 338,573,189 ordinary shares (excluding 24,817,479 ordinary shares issued to depositary bank as of March 31, 2023, for bulk issuance of American depository shares (ADSs) reserved for future issuances upon the exercise or vesting of awards granted under our share incentive plans), par value of US$0.0001 per share, were issued and outstanding. As of March 31, 2023, 18,927,261 options were granted and 15,049,943 options were outstanding, and 1,974,391 restricted share units (“RSUs”) were granted under our employee stock option plan. Each of our ADS represents five ordinary shares.
Conference Call and Webcast Details:
Monday, May 15, 2023 @ 8:00am ET
Investor domestic dial-in: (800) 715-9871
Investor international dial-in: (646) 307-1963
Conference ID: 2756776
Live webcast link: https://ir.gracellbio.com/news-events/events-and-presentations
A replay of the webcast will be available on ir.gracellbio.com shortly after the conclusion of the event for 90 days.
About FasTCAR
Introduced in 2017, FasTCAR is Gracell’s revolutionary next-day autologous CAR-T cell manufacturing platform. FasTCAR is designed to lead the next generation of cancer and autoimmune disease therapy and improve outcomes for patients by enhancing efficacy, reducing costs, and enabling more patients to access critical CAR-T treatment. FasTCAR drastically shortens cell production from weeks to overnight, potentially reducing patient wait times and probability for their disease to progress. Furthermore, FasTCAR T-cells appear younger and are more robust than traditional CAR-T cells, making them more proliferative and effective at killing cancer cells. In November 2022, FasTCAR was named the winner of the Biotech Innovation category of the 2022 Fierce Life Sciences Innovation Awards for its ability to address major industry obstacles.
About TruUCAR
TruUCAR is Gracell’s proprietary technology platform and is designed to generate high-quality allogeneic CAR-T cell therapies that can be administered “off-the-shelf” at lower cost and with greater convenience. With differentiated design enabled by gene editing of unique genes, TruUCAR is designed to control host vs graft rejection (HvG) as well as graft vs host disease (GvHD) without the need of being co-administered with additional immunosuppressive drugs.
About SMART CARTTM
SMART CARTTM is Gracell’s proprietary technology module designed to strengthen the functionality of CAR-T cells further, and aims to overcome tumor microenvironment (TME). SMART CARTTM includes altered expression of the receptor and signaling mechanism of an inhibitory TME molecule to enhance expansion and persistence and to reduce the exhaustion of CAR T cells. This design reverses and turns immunosuppressive signals of TME into stimulatory reactions of CAR-T cells. SMART CARTTM technology can be applied to many targets for the treatment of solid tumors.
About Gracell
Gracell Biotechnologies Inc. (“Gracell”) is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTTM technology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit www.gracellbio.com and follow @GracellBio on LinkedIn.
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GRCL reports earning on the 15th. IOVA should know by the end of May whether the FDA has accepted their BLA for review. That will be a big deal for IOVA. IOVA is also hoping for accelerated approval.
Blade
Blade, Thanks, I'll check them out :o)
I see GRCL is a Chinese company, early stage, but looks like they have almost 1.5 Bil in cash (per Yahoo) which is unusual. Btw, nice to see IMGN having success :o)
One fairly conservative one I found is Simulations Plus (SLP). Not a biotech per se, but their technology is used by biopharma companies to accelerate development. A nice 10 year chart, and I'm hoping it resumes its upward trajectory -
>>> Simulations Plus (SLP) is a premier developer of groundbreaking drug discovery and development simulation software, which is licensed and used for drug research by major pharmaceutical and biotechnology companies worldwide. <<<
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171750833
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Take a look at: CRDF, JSPR, IOVA, MRSN, GRCL
Bladerunner
Dew - Apellis Pharma - >>> APLS’ Syfovre has_impressive_first_month—contrary to my skepticism about the drug’s efficacy:
https://www.globenewswire.com/news-release/2023/05/04/2662038/0/en/Apellis-Pharmaceuticals-Reports-First-Quarter-2023-Financial-Results.html
APLS sold $18.4M of Syfovre during March (the commercial launch was 3/1/23). Some of this may be a stocking bolus by medical practices.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171843665
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>>> Apellis Pharmaceuticals, Inc. (APLS), a commercial-stage biopharmaceutical company, focuses on the discovery, development, and commercialization of therapeutic compounds through the inhibition of the complement system for autoimmune and inflammatory diseases.
It offers EMPAVELI for the treatment of paroxysmal nocturnal hemoglobinuria, cold agglutinin disease, C3 glomerulopathy and immune complex membranoproliferative glomerulonephritis, amyotrophic lateral sclerosis, and hematopoietic stem cell transplantation-associated thrombotic microangiopathy; and -
SYFOVRE for treating geographic atrophy (GA). The company also develops -
APL-2006, a bispecific C3 and VEGF inhibitor for treating wet age-related macular degeneration and GA;
APL-1030, a C3 inhibitor for the treatment of various neurodegenerative diseases;
and the combination of EMPAVELI and a small interfering RNA for reducing the production of C3 proteins by the liver.
It has a collaboration and license agreement with Swedish Orphan Biovitrum AB (publ) for development and commercialization of pegcetacoplan; and a collaboration with Beam Therapeutics Inc. focused on the use of Beam's base editing technology to discover new treatments for complement-driven diseases. The company was incorporated in 2009 and is based in Waltham, Massachusetts.
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https://finance.yahoo.com/quote/APLS/profile?p=APLS
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>>> Apellis Pharma's Newly Approved Drug Exceeds Sales Projections, Bullish Analyst Raises Expectations
Benzinga
Vandana Singh
May 5, 2023
https://finance.yahoo.com/news/apellis-pharmas-newly-approved-drug-195711302.html
Apellis Pharmaceuticals Inc (NASDAQ: APLS) reported Q1 revenues of $44.8 million, surpassing the consensus of $26.10 million and $14.38 million a year ago.
The company reported an EPS loss of $(1.56), higher than $(1.42) a year ago and missing the consensus of $(1.46).
Needham writes that Syfovre's sales of $18.4 million were well above their estimate of $5 million and the Street's $1.5 million estimates. The analyst has raised the price target to $110 from $80, with a Buy rating.
The management has tempered expectations for 2023 sales given the relatively short launch time and noted that demand and sales might be lumpy in 2023.
In February, the FDA approved Apellis' Syfovre (pegcetacoplan) for geographic atrophy (GA) secondary to age-related macular degeneration. Syfovre is the first and only FDA-approved treatment for GA.
The analyst has raised the 2023 Syfovre sales estimate to $113 million from $100 million, and it anticipates the pre-1Q23 Street 2023 estimate of $61.5 million to go up after the strong 1Q23 showing.
Empaveli sales of $20.4 million exceeded Needham's $22.0 million estimate.
Empaveli self-injector PDUFA was initially set for March 15, 2023, but FDA has extended its review of the sNDA for an undetermined amount of time. The company is awaiting further detail on timing.
Price Action: APLS shares are up 10.63% at $93.29 on the last check Friday.
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>>> Eli Lilly Surges On Promising Data From Late-Stage Alzheimer's Drug Trial
"This is the first Phase 3 trial of any investigational medicine for Alzheimer's disease to deliver 35% slowing of clinical and functional decline," Eli Lilly said.
The Street
by MARTIN BACCARDAX
MAY 3, 2023
https://www.thestreet.com/investing/stocks/eli-lilly-surges-on-promising-data-from-alzheimers-drug-trial
Eli Lilly (LLY) - shares moved firmly higher Wednesday after the drugmaker posted promising data from a late-stage trial of its developing Alzheimer's treatment.
Eli Lilly said the treatment, known as donanemab, slowed the progression of Alzheimer's in Phase 3 trial patients by 35%, when compared to placebo, with a 40% decline on the "ability to perform activities of daily living."
The results improve on Lilly's Phase 2 trial, which was published in late January, and suggest donanemab -- which targets amyloid plaque -- proteins found in spaces between nerve cells that can disrupt communication to the brain -- could find favor with the U.S. Food & Drug Administration.
The FDA rejected Eli Lilly's request for an accelerated review of donanemab earlier this year, citing "the limited number of patients with at least 12 months of drug exposure data provided in the submission." Eli Lilly said the speed at which donanemab reduced amyloid plaque meant that some patients left the Phase 2 study, known as Trailblazer, after six months, reducing its overall same size. (?)
Alzheimer's disease is a progressive brain disorder that affects more than 50 million people around the world. To date, no drug has been found to address the disease, which can accelerate into dementia and other more serious cognitive conditions.
"Over the last 20 years, Lilly scientists have blazed new trails in the fight against Alzheimer's disease by elucidating basic mechanisms of AD pathology and discovering imaging and blood biomarker tools to track the pathology," said Daniel Skovronsky Lilly's chief scientific and medical officer.
"We are extremely pleased that donanemab yielded positive clinical results with compelling statistical significance for people with Alzheimer's disease in this trial," he added. "This is the first Phase 3 trial of any investigational medicine for Alzheimer's disease to deliver 35% slowing of clinical and functional decline."
Eli Lilly shares were marked 3.7% higher in early Wednesday trading immediately following news of the trial data to change hands at $419.08 each.
Late last year, European drugmaker Roche AG said that trials of its gantenerumab, a drug used to treat patients with early-stage Alzheimer's, failed to reach the primary endpoint of preserving cognitive functions affected by the disease.
The results leave Biogen (BIIB) - which unveiled better-than-expected results from a late-stage study of its Alzheimer's treatment developed with Japan-based partner Eisai Co Ltd., as well as Eli Lilly, as potential market leaders in the multi-billion market.
Treatment pricing, however, has been a controversial issue and the U.S. Centers of Medicare and Medicaid Services noted in September that its decision to only cover treatment with Aduhelm -- Biogen's FDA-approved Alzheimer's drug -- if patients are enrolled in a clinical trial as a major factor in lowering overall premiums for Medicare Part B.
Biogen was forced to slash the price of Aduhelm by around 50%, to $28,200 per year, in order to help expand its potential reach following the CMS decision late last year.
Aduhelm, Biogen noted in earlier studies, has been show to erode amyloid beta, a plaque which builds up around the brain and can lead to neuron damage.
The FDA approved Aduhelm for the treatment of Alzheimer’s through its accelerated approval pathway, which can be used for a drug for a serious or life-threatening illness that provides a meaningful therapeutic advantage over existing treatments, last year.
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>>> Why long COVID could be a ticking time bomb for public health
Salon
by Philip Finkelstein
4-24-23
https://www.msn.com/en-us/health/medical/why-long-covid-could-be-a-ticking-time-bomb-for-public-health/ar-AA1ahhqo?ocid=hpmsn&cvid=9d045fab09154240833b24ee52f26fbe&ei=28
The 1918 influenza pandemic, commonly referred to as the Spanish Flu, infected approximately one-third (500 million) of the world's population (then 1.8 billion) and killed an estimated 50 million. With such a high mortality rate, even among young and healthy individuals, this acute infectious disease took its toll, erasing from existence nearly 3% of all people on Earth. But the damage did not stop there: across the globe, survivors of the initial viral infection reported "long flu" symptoms — profound fatigue, brain fog, depression, tremors, sleeplessness, and a litany of neurological disorders.
While the initial pandemic forced governments to organize a response to the sudden crisis, an epidemic of chronic illness may not raise alarms that spur us into immediate action.
This "long flu," an echo of sorts of the Spanish Flu epidemic itself, has its parallel in long COVID today — a similar cluster of symptoms that persist in those who were previously infected with COVID-19. And the similarities suggest that what we think of as long COVID is not necessarily a novel condition, but merely one more instance of the medical aftermath that accompanies certain infections.
The medical establishment calls this condition post-acute infection syndrome (PAIS). Back in 1918, these mysteriously persistent long flu symptoms wreaked havoc on human health and local economies. For example, many claim that debilitating lethargy caused by this post-viral syndrome led to the "famine of corms" in the region that is Tanzania today, as farmers lacked the energy to plant, harvest, and shear months after getting sick.
Around the same time, cases of a new brain-attacking disease called encephalitis lethargica started to emerge, affecting up to one million people worldwide. The cause of encephalitis lethargica remains one of the largest medical mysteries of the 20th century, though some scientists contend that the Spanish Flu may have been the trigger. The condition was colloquially known as "sleeping sickness," as those infected developed extreme fatigue, neurocognitive impairments, psychiatric illness, and movement disorders. A subset of these individuals fell into a semi-comatose state that lasted for decades. About one-third of encephalitis lethargica patients eventually died from respiratory failure caused by neurological dysfunction, while many survivors continued to suffer from ongoing Parkinson's-disease-like (neurocognitive) symptoms.
In 1969, as chronicled in his book "Awakenings," the neurologist Oliver Sacks discovered that temporary remission of these chronic symptoms, coined post-encephalitic parkinsonism, could be achieved through the use of the Parkinson's drug L-DOPA. Like with Parkinson's disease itself, the benefits of the drug wore off over time, but the finding indicated that encephalitis lethargica impacted the substantia nigra (the part of the brain that helps control movement).
We now have a plethora of information suggesting that COVID-19 is the latest addition to the list of infections spawning post-acute infection syndrome.
Although the medical community has long known that acute infectious diseases are not always entirely self-limiting, chronic sequelae (meaning the secondary symptoms that appear after an infection) receive little attention, remain under-researched, and continue to be misdiagnosed and overlooked by doctors. According to a study published in the scientific journal Nature, post-acute infection syndrome is associated with a number of infections, including Epstein Barr virus, cytomegalovirus, Lyme disease, Q fever, West Nile virus, Dengue fever, and the aforementioned influenza. Often presenting well after the initial infection, post-acute infection syndrome manifests as a complex and variable disorder, typically entailing severe fatigue, gastrointestinal issues, confused sensory perception, and neurocognitive abnormalities.
Despite the growing pool of data from patients suffering from post-acute infection syndrome, a comprehensive explanation of the biological mechanisms by which the syndrome's symptoms arise has yet to be established. This lack of scientific understanding creates an untold degree of hardship for those dealing with severe and chronic sequelae of infections. Worse, when doctors cannot find a biological explanation for reported symptoms, patients are often left with little recourse and the feeling that their doctor believes the cause of their suffering is rooted in mental illness.
Years into our current pandemic, we now have a plethora of information suggesting that COVID-19 is the latest addition to the list of infections spawning post-acute infection syndrome; that is, "long COVID." Multinational surveys have been conducted, with thousands upon thousands of adult participants reporting that recovery from an initial COVID infection took more than 35 weeks. Some of these studies highlight the fact that new ailments are reported 6-12 months after an initial COVID infection, which most commonly include fatigue, post-exertional malaise, and cognitive dysfunction.
According to the CDC, in June 2022, almost one in five American adults who had COVID-19 still had long COVID. This statistic seems to be borne out by my anecdotal experience; I have met with and spoken to many people around the world who have lost their sense of smell, had to take medical leave, been fired from work, seen a drop in their focus during school, experienced overwhelming exhaustion and migraines, or become depressed after being infected with COVID. My home state's newspapers recently shared the sad medical saga of a man, Charlie Vallee, whom I grew up with in Vermont. After only mild respiratory symptoms during his initial bout of COVID-19, Vallee went on to develop such severe long COVID symptoms, including brain fog, that he left his job as an intelligence officer in D.C. and tragically took his own life. His family has set up a foundation to fund long COVID research in the hopes of one day understanding how this pernicious form of post-acute infection syndrome can cause an otherwise happy and healthy individual to die by suicide.
In other words, long COVID is affecting more people than we likely know. And it eerily parallels other post-acute infection syndrome scenarios throughout history, including those potentially linked to epidemics of parkinsonism. In other words, the threat of long COVID could lead to a future public health catastrophe, much as the "long" effects of the Spanish Flu did a hundred years ago. Unfortunately, the pharmaceutical and medical community are not approaching long COVID with the same fervor that they had for COVID-19. As a result, there is a real danger that a broad-scale investigation into the origin of long COVID is postponed or neglected by funding agencies and the medical establishment.
While the initial pandemic forced governments to organize a response to the sudden crisis, an epidemic of chronic illness may not raise alarms that spur us into immediate action. Like climate change, a gradually-evolving threat, especially one perceived to be far away, is much harder to address. But the threat here is not that far off, as emerging science reveals — which is why it is of grave importance that we push for an explanatory theory of long COVID (and post-acute infection syndrome) that can fully account for the totality of symptoms observed after an initial infection with SARS-CoV-2 despite no clinical findings of active infection.
Multiple studies published in the journal Nature (one published last year and one published in February of this year) explain how COVID-19 has the ability to trigger the aggregation of proteins within the human body. The research suggests that SARS-CoV-2 can cause normal proteins to abnormally misfold. These misfolded proteins are known as "amyloids," which are toxic to cells when they build up.
Specifically, amyloids occur when proteins misfold into twisted clumps and form long fibers, hindering cellular function. These so-called clumps can start stacking excessively, creating harmful deposits in the body — sort of like cholesterol in the bloodstream but at the cellular level. When misfolding of a protein named "alpha-synuclein" in the nervous system occurs, the amyloid buildup this causes in a neuron can lead to the formation of what is known as a "Lewy body," which is resistant to breakdown and clearance. Think of it as plaque buildup in the nervous system. Lewy bodies spread as pieces of these amyloids break away and seed the formation of new Lewy bodies in neighboring neurons.
The scariest thing about this? Misfolded alpha-synuclein is a hallmark of Parkinson's disease, Lewy body dementia, multiple system atrophy, and pure autonomic failure — all neurodegenerative diseases collectively known as synucleinopathies. And what can cause alpha-synuclein misfolding? Genetic mutations, exposure to certain toxins, and infections. COVID-19 may be one such infection — and that means long COVID symptoms may be a reflection of a developing neurological disorder.
Alarmingly, two studies published by the Mayo Clinic and the Medical University Innsbruck corroborate the findings in the Nature articles, recording signs of dream-enactment sleep disorder among one-third of patients after being infected with COVID-19. Over 80% of patients with dream-enactment sleep disorder go on to develop a Parkinson's-like disease within two decades.
So we need to ask the question: is the recent rise of dream-enactment sleep disorder after COVID related to neurodegeneration? Preliminary research from Stanford University and Beth Israel Deaconess Medical Center suggests that this may be the case, as disease-causing clumps of alpha-synuclein have been discovered in some long COVID patients.
So how does all of this connect? Basically, if dream-enactment sleep disorder is more common in those who have had COVID, and the vast majority of those who suffer from this kind of sleep disorder ultimately develop neurological diseases like Parkinson's, then COVID-19 could lead to an explosion of these diseases in the coming years.
This is not mere speculation; animal models further substantiate these claims. For example, a study of macaques demonstrated that SARS-CoV-2 induces Lewy body formation (a feature of Parkinson's disease), even after an asymptomatic infection. And, whether or not COVID is determined to be a direct cause of Parkinson's, it could also accelerate the disease course in patients who are predisposed. This was exemplified by a study performed by infecting mice with COVID-19, which found that the virus made the brain more susceptible to toxic compounds known to cause Parkinson's disease. The lead researcher on this study, Richard Smeyne, PhD, who serves as Chair of the Department of Neuroscience at Thomas Jefferson University and Director of the Jefferson Comprehensive Movement Disorder Center reviewed this article before publication, affirming what has been outlined and reiterating his study's findings: "Should the predicted risk from SARS-CoV-2 manifest, the diverse consequences would represent a substantial burden on patients, families, and society."
Dr. Smeyne elaborated on the seriousness of these findings, telling Salon, "Our studies in mice predict a 30-50% increase in Parkinson's risk for those moderately to severely infected with the Alpha variant. While on an individual basis this only changes a person's risk from 2% to 3% for developing Parkinson's, over the whole of the population we would expect to see millions more develop Parkinon's disease than would have if not for their COVID infection."
"We still have to examine if the newer strains of SARS-CoV-2 also have the potential to increase the risk for Parkinson's disease."
A prominent theory for explaining Parkinson's disease, put forth by Heiko Braak, a German doctor who studies Parkinson's, aligns well with all these long COVID findings. It states that Parkinson's is caused by a pathogen affecting either the nasal cavity or digestive system, thereby first initiating protein misfolding in the peripheral nervous system before spreading into the brain later on (sometimes decades later). This is why the onset of Parkinson's often entails autonomic dysfunction — which means involuntary processes like heart rate, blood pressure, respiration, etc. are compromised. As autonomic dysfunction is a common symptom of long COVID, it is thus possible that the post-acute infection syndrome mechanism responsible for long COVID progresses to the central nervous system over time and could eventually present as Parkinson's disease or a similar disorder.
In other words, while long COVID is not caused by the lingering viral remnants of COVID-19 per se, the initial infection could be precipitating amyloid buildup and Lewy body formation. If this is so, long COVID would mimic a chronic or slowly-evolving infection caused by the virus, similar to other post-acute infection syndrome cases, with the symptoms fluctuating and emerging unpredictably as the amyloids slowly spread throughout the nervous system.
Braak's hypothesis was based on autopsy data, which indicated a distinct pattern of aggregated alpha-synuclein in those who died from/with Parkinson's disease. However, according to Dr. Smeyne, "As of yet, there is no good non-invasive marker for alpha-synuclein aggregation in living patients, which is why The Michael J. Fox Foundation is offering a $2 million prize to any person or group that successfully develops such a marker."
The way forward
To investigate these claims, larger studies need to evaluate patients with long COVID for markers of Parkinson's-like diseases, such as misfolded alpha-synuclein. A clinical trial is currently underway to do just that — so that the history of post-encephalitic parkinsonism in the years following the Spanish Flu does not repeat itself. Considering the mounting evidence, it is crucial that we address the long COVID public health emergency promptly, to provide answers to those suffering from long COVID and prevent a potential increase in "post-COVID parkinsonism."
When asked about his outlook for the future, Dr. Smeyne said, "We are entering a period where we will have to learn to live with COVID being present as a fact of life. This means we still have to examine if the newer strains of SARS-CoV-2 also have the potential to increase the risk for Parkinson's disease and whether vaccination against this virus can reduce the increased Parkinson's risk, as has been shown following vaccination against influenza. Once we determine the answers to these questions, we can begin to look at other ways to interfere with the process."
Salon then asked what it will take to definitively prove whether COVID-19 can trigger a Parkinson's-like disease and whether long COVID is in fact the early stages of such a disease. Dr. Smeyne responded, "My best guess is we will need anywhere from five to ten years from the initial outbreak to see any statistically measurable effect."
Encouragingly, Dr. Smeyne went on to say, "One bright spot in these observations is that there is a considerable period, often about a decade, between viral exposure and the development of a neurological disease like Parkinson's. And there are currently scientists devoting their lives' efforts to find ways to solve this problem — the lag between exposure and disease gives me hope that we will find a way to stop the progression from infection to disease in its tracks."
There have been more than 760 million globally documented cases of COVID-19, with the real number of cases, including asymptomatic cases, presumably much higher. More than 750 million have survived, but, as reported, long COVID is occurring in 20-30% of these cases, meaning that hundreds of millions of people could be at higher risk of developing Parkinson's disease or other neurodegenerative issues later in life. If it comes to pass, the public health resources required to help will be astronomical. It behooves us to study long COVID now, lest we end up in such a crisis.
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>>> Simulations Plus (SLP) is a premier developer of groundbreaking drug discovery and development simulation software, which is licensed and used for drug research by major pharmaceutical and biotechnology companies worldwide.
https://finance.yahoo.com/news/4-low-beta-tech-stocks-143202937.html
Currently, Simulations Plus has a Zacks Rank #2. It has a beta of 0.54. Shares of SLP have climbed 15.9% YTD.
Lancaster, CA-headquartered SLP’s performance is being driven by strength in its Services revenues, which increased 4% to $5.3 million in second-quarter fiscal 2023. In March, the company partnered with the Sino-American Cancer Foundation to boost the development of anticancer therapies. Earlier in the same month, it collaborated with the Institute of Medical Biology of the Polish Academy of Sciences to design new compounds for the ROR?/ROR?T nuclear receptors. As part of the agreement, the company is leveraging artificial intelligence/machine learning technologies in the ADMET Predictor platform for the development of new compounds.
The Zacks Consensus Estimate for SLP’s fiscal 2023 earnings is pegged at 66 cents, unchanged over the past seven days. The consensus mark for fiscal 2024 earnings has also remained steady for the past seven days at 71 cents, suggesting an 8.3% year-on-year rise.
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>>> Skin cancer vaccine (mRNA) an 'exciting' advance in reducing risk of melanoma relapse, trial shows
NBC News
by Linda Carroll and Reynolds Lewis
April 17, 2023
https://news.yahoo.com/mrna-cancer-vaccine-exciting-advance-170100554.html
In 2019, Gary Keblish got a diagnosis from his surgeon that left him stunned. The flat, dark-brown mole he’d had on his back for as long as he could remember had turned into a melanoma that was already advanced, putting him at risk of dying.
“I felt numb,” the Brooklyn teacher, 61, said in an interview.
Fortunately, Keblish was able sign on for a small clinical trial testing a preventive vaccine that might possibly keep the disease from coming back.
The trial focused on a personalized vaccine using mRNA technology that used mutations to target mutations unique to a patient’s cancer but not the healthy cells in the body. All participants in the trial would receive the immunotherapy drug Keytruda (pembrolizumab), the standard of care for high-risk melanoma patients like Keblish. Two-thirds of the participants would also receive the vaccine.
Keblish was one of those who received the vaccine — which teaches the body’s immune system to recognize cancer cells as different from normal cells so that, working along with the immunotheraoy drug, it can attack them.
After two years, Keblish's cancer hasn't returned.
Personalized cancer vaccine shows benefit
On Sunday, the results of the phase 2 trial, which showed that the combination of the vaccine and immunotherapy reduced the risk of recurrence by nearly half, were presented at the annual meeting of the American Association for Cancer Research.
It's the first randomized, controlled trial to show a benefit from this type of cancer vaccine, said senior investigator Dr. Jeffrey Weber, a deputy director of NYU Langone’s Perlmutter Cancer Center and a professor of medicine at the NYU Grossman School of Medicine.
To test the effectiveness of the vaccine, the international team of researchers recruited 157 melanoma patients whose tumors had been surgically removed and who were at high risk of experiencing a recurrence of their cancers. Fifty patients received only the immunotherapy medication and 107 also got the personalized vaccination.
One of the ways cancer evades the immune system is to fool the body into thinking the threat is over, at which point the natural braking system that prevents the immune system from staying constantly on kicks in. Weber compares the way pembrolizumab works to cutting a stuck brake cable on a car so it can go forward.
Once the system’s braking system has been partially disabled, “the immune system works really well,” Weber said, adding that the downside of “cutting brake cable” is that the immune system stays turned up and some people end up with inflammation and something that resembles an autoimmune disease.
One other way cancer can avoid being destroyed is through mutations, so the immune system’s soldiers cease to recognize it as a threat.
That’s where the personalized mRNA vaccine comes in. After a patient’s tumor is removed, doctors identify proteins that are specific to that person’s tumor and no other cells in the body. As many as 34 proteins from a patient’s tumor were then the target of the vaccine.
In the trial, 40% of the patients who received only the immunotherapy drug had a recurrence of their cancer during the two-year follow-up. In comparison, 22.4% of patients who got the drug plus the vaccine had a recurrence, leading to a difference of 44% between the two groups.
The new findings are significant, said Dr. Antoni Ribas, a professor of medicine at the University of California, Los Angeles, and director of Tumor Immunology Program at UCLA’s Jonsson Comprehensive Cancer Center.
It’s the first time a cancer vaccine has been shown to have this level of benefit, close to a 50% decrease in the risk of relapse,” said Ribas. “It tells us these vaccines actually work and can turn on an immune response against the patient’s own cancer."
The trial’s results are “very exciting,” said Dr. Thomas Marron, director of the Early Phase Trials Unit at the Tisch Cancer Institute and an associate professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.
“Once the tumor is removed, we know it can come back because tiny microscopic bits have traveled elsewhere in the body and set up shop there,” Marron said. The recurrence often appears quickly, between six months and two years, he said.
The beauty of the vaccine in this study is that it targets up to 34 mutations, Marron said. “That’s like taking 34 shots on goal," he said. You’re teaching the immune system to recognize 34 different things that are unique to that cancer.”
The researchers anticipate the phase 3 trial, scheduled to launch this summer, to show similar results. With follow-up and monitoring, it could be at least two years before data is registered with the Food and Drug Administration and up to three years before the vaccine combination would be approved for use in patients, Weber said.
Still, it's an exciting advance in the field of cancer vaccines, particularly for stopping melanoma, the deadliest form of skin cancer, experts said.
The study is “important because it’s the first randomized study of a cancer vaccine with a clinically meaningful endpoint: stopping tumors from coming back,” said Dr. Margaret Callahan, research director of the Memorial Sloan Kettering Immunotherapeutics Program, who expressed cautious optimism about the findings.
“This is an exciting advance in the field of cancer vaccines, an area notoriously tough to make progress in,” Callahan said.
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>>> Merck to buy Prometheus Biosciences for about $11 billion
Reuters
4-16-23
https://www.msn.com/en-us/money/companies/merck-to-buy-prometheus-biosciences-for-about-11-billion/ar-AA19VksJ?OCID=ansmsnnews11
(Reuters) - Merck & Co has agreed to acquire Prometheus Biosciences Inc for about $10.8 billion to bolster the company's presence in immunology, the companies said on Sunday.
The joint statement said that Merck, through one of its subsidiaries, will pay $200 per share for the biotechnology company that specializes in products for treatment of immunological diseases. That represents a 75% premium to the $114.01 closing price for Prometheus shares on Friday.
Prometheus had a market capitalization of $5.42 billion at Friday's close.
Merck has been looking for deals to protect itself from eventual revenue loss as patents on its cancer immunotherapy Keytruda begin to expire towards the end of the decade.
"The agreement with Prometheus will accelerate our growing presence in immunology where there remains substantial unmet patient need. This transaction adds diversity to our overall portfolio," said Merck Chairman and Chief Executive Robert Davis.
The deal, which was first reported by the Wall Street Journal, is expected to close in the third quarter of the year, the companies said.
Merck in February forecast 2023 earnings below Wall Street estimates and an expected steep decline in sales of its COVID-19 antiviral treatment.
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>>> As superbug infections grow more common, the world is running out of drugs to treat them
NBC News
by Caroline Hopkins
March 29, 2023
https://investorshub.advfn.com/secure/post_new.aspx?board_id=37829
Late last year, one of Dr. Vance Fowler’s patients — a man in his 60s who’d returned to North Carolina from visiting his family in Nepal — died of a bacterial infection. He’d been treated at a top U.S. hospital with access to the strongest antibiotics. But the infection, a drug-resistant strain of E. coli, surged on.
“Antibiotic resistance is a real problem that, with little or no warning, can affect the lives of any of us at any time,” said Fowler, an infectious disease specialist at Duke Health. “We don’t have enough drugs.”
Health officials have warned the public about antibiotic resistance for decades. That’s become more urgent in light of an upcoming World Health Organization report tallying only a handful of new antibiotics in development.
Preliminary data from the report, released by the WHO this month, paint a dire picture: Just 27 new antibiotics for the most threatening infections are in the clinical trial stage of drug development. In contrast, there were more than 1,300 cancer drugs in clinical trials in 2020, according to a report from the trade organization Pharmaceutical Research and Manufacturers of America.
Of the antibiotics in trials, the WHO considers only six of them innovative enough to overcome antibiotic resistance, and just two capable of targeting the most resistant bacteria. Agency officials will present the full report during the European Congress of Clinical Microbiology and Infectious Diseases next month.
There’s no telling whether this handful of new drugs in clinical trials will work, either. From 2017 to 2021, just one new antibiotic, cefiderocol, was approved that could treat the superbugs on WHO’s most critical list, including strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. These pathogens can cause a range of potentially severe infections in the lungs, urinary tract, ears, blood, open wounds, or even the brain and the spinal cord.
Resistance on the rise
Drug-resistant bacteria are growing more common. In the United States alone, the Centers for Disease Control and Prevention estimates more than 2.8 million people develop drug-resistant infections each year, and more than 35,000 people die as a result. Certain drug-resistant strains of gonorrhea are on its list of urgent superbugs, as is Clostridioides difficile, or C. diff, which can cause life-threatening diarrhea and colon inflammation. The CDC estimates 12,800 people die of C. diff each year.
One of the most common superbugs in the U.S., methicillin-resistant Staphylococcus aureus, or MRSA, kills 9,800 people each year. MRSA can spread rapidly in long-term care facilities and hospital settings, where cases spiked 13% during the first year of the Covid pandemic.
Infections from the drug-resistant Shigella bacteria, often resulting in severe diarrhea and stomach pain, have been climbing at an alarming rate, too. In February, the CDC warned that last year, 5% of Shigella infections were “extensively drug-resistant” — meaning they didn’t respond to a number of antibiotics — up from zero percent in 2015. Shigella can spread through sexual contact, particularly among men who have sex with men.
Bacteria aren’t the only culprit. In the U.S., antifungal drug-resistant infections from the fungus Candida auris increased 60% in 2020, according to the CDC.
The WHO has identified 12 resistant superbugs deemed “priority pathogens,” and the CDC tracks a list of 18 drug-resistant bacteria and fungi.
Globally, more than 5 million people die from antibiotic resistance, outnumbering deaths from HIV, tuberculosis and malaria combined, said Valeria Gigante, a team lead within the WHO’s antimicrobial resistance division.
“Antimicrobial resistance is one of the top global health threats facing humanity,” she said. “We shouldn’t call it a silent pandemic anymore. We should be loud and clear: it is indeed a pandemic.”
Bacteria and fungi are more likely to develop resistance the more they’re exposed to antibiotics or antifungals. In the case of Fowler’s patient, the specific E. coli bacteria strain had a gene that makes a protein called NDM-1, which can break down even the strongest, last-resort antibiotics, called carbapenems. Right now, most E. coli strains — there are more than 700 — aren’t deadly. But beyond E. coli, several strains of Klebsiella, Enterobacter and Acinetobacter already have this gene, and according to Fowler, more may soon acquire it.
“They don’t need a passport to travel,” Fowler said. And bacteria can swap DNA “kind of like baseball cards.”
“Maybe five or 10 years down the road, the U.S. will be facing resistance patterns reasonably similar to what we’re facing in India or Greece,” said Dr. Venkatasubramanian Ramasubramanian, president of the Clinical Infectious Diseases Society of India. Both countries have seen outbreaks of bacteria resistant to the strongest, last-resort antibiotics. “It’s a matter of time.”
The WHO says the rate of antibiotic resistance is accelerating. From 1970 to 2000, the average time it took for resistance to develop to new antibiotics was just two to three years, down from the 11-year average from 1930 to 1950. Resistance skyrocketed during the early days of the pandemic when many health systems overused antibiotics, which have no impact on Covid because it is caused by a virus, not a bacterium.
Where are all the new drugs?
The economic model for new drugs — pharmaceutical companies invest large sums upfront to test a drug’s safety and efficacy, then earn that money back in sales once it’s approved — “doesn’t work for antibiotics,” Ramasubramanian said.
Developing one new antibiotic can take up to two decades and usually costs $568 million to $700 million according to PhRMA. And just 1 in 30 of these drugs are ultimately approved to treat patients. But unlike medicines meant for widespread use, there’s an international push to use fewer antibiotics. Excessive or unnecessary antibiotic use ups the odds of a pathogen developing resistance.
“With a new antibiotic, we say, ‘don’t use it,’ or ‘use it sparingly so it lasts longer,’” Ramasubramanian said. “It is not an attractive proposition for anyone in the industry.”
Some countries have rolled out what they call “antibiotic stewardship programs.” These encourage doctors to prescribe the drugs only when there’s a clear need. In the U.S., for instance, the CDC offers training courses and guidelines to help curb antibiotic use and stave off resistance.
Even in cases where antibiotics are truly necessary, they’re often prescribed for just days or weeks, making them far less lucrative than long-term, daily-use drugs for chronic conditions such as blood pressure or diabetes.
“At the end of the day, the ‘supply and demand’ model is not tenable for antibiotics,” Fowler said.
No easy answer
If drugmakers don’t start developing new antibiotics soon, the world may be facing a “doomsday scenario,” WHO officials warned.
More people could die from once-treatable infections, such as bacterial pneumonia, gonorrhea or salmonella. Those who need antibiotics most, like immunocompromised people and those undergoing cancer treatment, will be most vulnerable.
“We have arrived in the post-antibiotic era,” Ramasubramanian warned in a statement March 15. “The current antibacterial pipeline is woefully insufficient to make a difference in tackling the ongoing threat of antibiotic resistance.”
Fowler, who wasn’t involved in the WHO report, agreed with the organization’s use of bold “doomsday” language. “The WHO is 100% spot-on,” he said. “I was thrilled to see them make such a strong statement because I think it’s true.”
While there’s no single fix for catalyzing new antibiotic development, Gigante said, government funding and policy could help move the needle. For instance, some countries have devised new economic models for incentivizing antibiotic development.
In the U.S., lawmakers are debating a legislation called the PASTEUR Act that would pay pharmaceutical companies contractually to make these critical new drugs available.
“It would fundamentally be a Netflix-like subscription model,” Fowler said. Drug companies wouldn’t have to rely on the minimal revenue they’d get selling their antibiotics on the commercial market. The proposed model has been controversial and hasn’t become law, but it’s an example of the type of “new economic model” WHO officials like Gigante want policymakers to explore.
U.S. taxpayer dollars do support some new antibiotics research already. For instance, Fowler leads a program called the Antibacterial Resistance Leadership Group, which funds new trials with grants from the National Institutes of Health.
“It’s an enormous amount of money, but there’s a great deal more that’s needed,” he said.
Better tests could help
Beyond calling for new antibiotics, the WHO officials want to see better, faster, ways of diagnosing bacterial infections. Right now, for the first 48 hours or so after a patient comes in with an infection, “you don’t know what germ you’re treating,” Fowler said.
The more quickly and accurately doctors zero in on the specific bug infecting their patients, the less likely they’ll be to prescribe antibiotics that won’t work, which could cause more resistance.
The diagnostic process involves collecting a swab, sending it to a lab, growing the bacteria from that swab until there’s enough to test, then, while still in the lab, trying out a bunch of different antibiotics to see which will work. It can take days or weeks, and the sickest patients can’t wait that long.
“It’s not through any lack of good clinical practice, but the state-of-the-art in treating infection in 2023 is an educated guess,” Fowler said. “It’s frightening when you think about it.”
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>>> DNA from Beethoven's hair reveals new details into his cause of death over a century later: study
Researchers discover Beethoven was genetically predisposed to liver disease and had hepatitis B in the months before his death
By Elizabeth Pritchett
Fox News
https://www.foxnews.com/health/dna-beethovens-hair-reveals-new-details-cause-death-centuries-later-study
A genetic study conducted on locks of Ludwig van Beethoven's hair revealed more details about the composer's death at a relatively young age in March 1827.
The University of Cambridge biological anthropologist Tristan Begg, the lead researcher in the study "Genomic analyses of hair from Ludwig van Beethoven," which was published in Current Biology on Wednesday, said eight strands of hair attributed to the German musician were tested in hopes of explaining potential underlying genetic and infectious causes of his illnesses.
It was already known that Beethoven, who died at the age of 56 from a protracted illness, began losing his hearing in his 20s and was functionally deaf by his mid-40s. He was also known to have experienced severe abdominal pains and chronic bouts of diarrhea since he was 22.
Though the study did not find a primary cause for his hearing loss or gastrointestinal problems, it shed light on other health issues the composer experienced during his lifetime.
Five of the eight strands of hair tested were found to be "perfect genetic matches" and were deemed "almost certainly authentic," the study said, allowing researchers to determine Beethoven had a genetic predisposition for liver disease – something that was thought to have contributed to his death.
The testing also discovered that the famous composer had a hepatitis B infection during the months prior to his death, at the least.
Researchers concluded that his genetic predisposition and heavy alcohol consumption presented "plausible explanations" for Beethoven's severe liver disease.
During the study, researchers also came across an unexpected result as an analysis of Y chromosomes from five living members of the Van Beethoven patrilineage compared with the DNA from Beethoven's hair revealed a mismatch in paternal ancestry generations before his birth.
"This finding suggests an extrapair paternity event in his paternal line between the conception of Hendrik van Beethoven in Kampenhout, Belgium in c.1572 and the conception of Ludwig van Beethoven seven generations later in 1770, in Bonn, Germany," Begg wrote.
The study also debunked a forensic investigation completed in 2007 that suggested lead poisoning could have sped up his death, if not the primary cause for the symptoms that ultimately claimed his life.
Though lead poisoning was probable due to drinking from lead vessels and medical treatments of the time that used lead, the hair used to complete that study nearly 16 years ago was found to have come from an unknown woman, not the composer.
Researchers said the hairs used in the study were gathered from public and private collections during the last six years of Beethoven's life.
Following Beethoven's death on March 26, 1827, various researchers and medical professionals studied the cause of his hearing loss – something the composer had requested in writing years prior.
He initially wanted his favorite physician, Dr. Johann Adam Schmidt, to reveal his health struggles to the public, but Schmidt died before Beethoven.
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Vertex Pharmaceuticals - >>> Vertex Pharmaceuticals (VRTX 1.23%) has remained the premier presence in the cystic fibrosis treatment space for over a decade now since its first therapy to treat the underlying factors that cause the genetic disease was given the green light by the U.S. Food and Drug Administration.
https://www.fool.com/investing/2023/03/09/2-top-stocks-to-buy-in-march-and-hold-forever/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Since that time, Vertex has seen its portfolio of CFTR modulators -- the class of drugs that work to correct the root cause of cystic fibrosis -- expand to four approved therapies, and it remains the only company with approved CFTR modulators on the market at the time of this writing.
While its portfolio of top-selling therapies faces consistent and growing demand -- management estimates that as many as 20,000 cystic fibrosis patients could take its CFTR modulators but aren't yet doing so -- Vertex is looking toward future sources of growth to spur its business and financials forward in the years ahead.
Its current pipeline includes a non-opioid drug candidate for acute pain, a cystic fibrosis drug for patients who can't take CFTR modulators (management estimates that more than 5,000 patients fit this category), and a potential one-time functional care for two rare blood disorders, for which it's in the process of undergoing regulatory submissions.
The company is also wading into the lucrative diabetes care market. Last year, Vertex finished its acquisition of ViaCyte, a company that is working on stem cell therapies to treat type 1 and type 2 diabetes. The cystic fibrosis treatment market is set to reach a valuation of $32 billion by the year 2027, achieving a compound annual growth rate of more than 24% from its 2019 valuation of about $5 billion.
However, the broad opportunities within this space are just the tip of the iceberg for the long-term potential that Vertex appears to have as it continues to explore lucrative yet underpenetrated segments of the rare-disease drug market. For investors searching for a healthcare stock in which to retain a multi-year, buy-and-hold investment, Vertex looks like a compelling choice to consider.
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Name | Symbol | % Assets |
---|---|---|
Regeneron Pharmaceuticals Inc | REGN | 2.77% |
Moderna Inc | MRNA | 2.65% |
Gilead Sciences Inc | GILD | 2.43% |
Vertex Pharmaceuticals Inc | VRTX | 2.32% |
Biogen Inc | BIIB | 2.28% |
United Therapeutics Corp | UTHR | 2.26% |
Biomarin Pharmaceutical Inc | BMRN | 2.25% |
Seattle Genetics Inc | SGEN | 2.16% |
Exelixis Inc | EXEL | 2.06% |
ACADIA Pharmaceuticals Inc | ACAD | 2.04% |
Name | Symbol | % Assets |
---|---|---|
Regeneron Pharmaceuticals Inc | REGN | 4.88% |
Gilead Sciences Inc | GILD | 4.58% |
Qiagen NV | QGEN | 4.48% |
Biogen Inc | BIIB | 4.28% |
Seattle Genetics Inc | SGEN | 4.08% |
United Therapeutics Corp | UTHR | 3.93% |
Vertex Pharmaceuticals Inc | VRTX | 3.89% |
ACADIA Pharmaceuticals Inc | ACAD | 3.75% |
Biomarin Pharmaceutical Inc | BMRN | 3.69% |
Alnylam Pharmaceuticals Inc | ALNY | 3.53% |
Name | Symbol | % Assets |
---|---|---|
Pacific Biosciences of California Inc | PACB | 6.85% |
Teladoc Health Inc | TDOC | 5.94% |
CRISPR Therapeutics AG | CRSP | 5.77% |
Twist Bioscience Corp | TWST | 5.72% |
CareDx Inc | CDNA | 3.87% |
Iovance Biotherapeutics Inc | IOVA | 3.59% |
Exact Sciences Corp | EXAS | 3.58% |
Fate Therapeutics Inc | FATE | 3.47% |
Invitae Corp | NVTA | 3.42% |
Personalis Inc | PSNL | 3.26% |
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