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Sigma-1 Receptor -
>>> There has been much interest in the sigma-1 receptor and its role in age-related neurodegenerative diseases such as Alzheimer's disease. During healthy ageing, the density of sigma-1 receptors has been to increase. However, in diseases such as Alzheimer's disease, there appears to be a reduction in sigma-1 receptor expression. It has been suggested that targeting the sigma-1 receptor along with other receptors could increase neuron survival and function in neurodegenerative disease.[15] The activation of autophagy has also been suggested as a downstream mechanism linked to sigma-1 receptor activation.[32] <<<
https://en.wikipedia.org/wiki/Sigma-1_receptor
>>> The sigma-1 receptor (s1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor.[5] In humans, the s1 receptor is encoded by the SIGMAR1 gene.[6][7]
The s1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system.[8] It has been implicated in several phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, bipolar disorder, and cancer.[9][10] Much is known about the binding affinity of hundreds of synthetic compounds to the s1 receptor.
An endogenous ligand for the s1 receptor has yet to be conclusively identified, but tryptaminergic trace amines and neuroactive steroids have been found to activate the receptor.[11] Especially progesterone, but also testosterone, pregnenolone sulfate, N,N-Dimethyltryptamine (DMT) and dehydroepiandrosterone sulfate (DHEA-S) bind to the s1 receptor.[12]
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>>> Autophagy is a highly conserved eukaryotic cellular recycling process. Through the degradation of cytoplasmic organelles, proteins, and macromolecules, and the recycling of the breakdown products, autophagy plays important roles in cell survival and maintenance.<<<
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Pay attention everyone !!!!!
DR. BENNETT: But what it accounts for is the fact that this side effect is undoubtedly not rare. The cytochrome P450, out of 25 people we tested, or 54, we had 55 percent with the genetic – (inaudible). So the reason why people are not being protected is not because this is rare but because doctors won’t listen to it and won’t report it and won’t say anything about it and won’t count this. So we 100 percent believe this is a fairly common side effect, and if you walk around the world and talk to people you meet socially on the plane or at a restaurant or anywhere else, they say, this happened to me, happened to my aunt, my grandma, my mother, my brother.
>>> The Gut Microbiome: Unleashing the Doctor Within
Dexter Shurney, MD, MBA, MPH
Am J Lifestyle Med. 2019 May-Jun; 13(3): 265–268.
PMCID: PMC6506970
PMID: 31105489
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506970/#:~:text=Not%20surprisingly%2C%20it%20was%20Hippocrates,that%20reside%20in%20the%20gut.
Wisdom From the Past
Hippocrates said,
Everyone has a doctor in him or her; we just have to help it in its work. The natural healing force within each of us is the greatest force in getting well. Our food should be our medicine. Our medicine should be our food.
As we continue to embark on the transformation of health care, it will be increasingly important to educate and empower our patients about their body’s amazing ability to heal itself. While this is not always an easy task, new research continues to provide us, as lifestyle medicine practitioners, with new ways to deliver our message. Perhaps no research is quite as exciting for lifestyle medicine as that of the human gut microbiome and its incredible and undeniable impact on human health.
Not surprisingly, it was Hippocrates who also coined the phrase, “All diseases begin in the gut.” While 2000 years of time and research has demonstrated that not all diseases originate in the gut, an increasing number of conditions are linked to the complex ecosystem of microbes that reside in the gut. The most promising part? We have the unique ability to manipulate this ecosystem, and health outcomes, through practical methods, many of which just so happen to be the pillars of lifestyle medicine.
The Human Microbiome
The human gastrointestinal (GI) tract is the complex plumbing system within; it is our first line of defense and our largest interface between the outside world. It is the microbial ecosystem, referred to as the gut microbiome, that is partially responsible for maintaining human health and is also associated with various diseases.
‘It is the microbial ecosystem, referred to as the gut microbiome, that is partially responsible for maintaining human health and is also associated with various diseases.’
Trillions of microorganisms survive in our intestines that have protective, structural, and metabolic roles. Metabolically, the gut microbiota functions to produce vitamins and synthesize amino acids. It is also involved in bile acid biotransformation and the fermentation of nondigestible substrates into short-chain fatty acids, which further stimulates the absorption of salts and water. The microbiome ensures protection from pathogenic colonization by competing for attachment sites and nutrients as well as through its ability to produce and secrete antimicrobials. In addition, healthy gut microbiota are essential for the development and homeostasis of the immune system. Structurally, certain bacteria in the microbiome have been shown to strengthen the mucus layer of the intestinal wall, which works as an obstacle to the uptake of proinflammatory molecules and antigens. Other bacteria are involved with strengthening the tight junctions of intestinal cell wall, which is partially responsible for keeping pathogens from entering the bloodstream.1
Dysbiosis is a term used to refer to a microbiota community associated with a diseased state that can be differentiated from the microbiota community associated with a healthy control state. Many factors can alter the ecosystem of the GI tract including antibiotics, psychological and physical stress, radiation, altered peristalsis, and dietary changes.2 The exact relationship between dysbiosis and various disease pathogenesis is somewhat uncertain mainly due to the lack of definitive research in this area. It does appear clear that there is a bidirectional relationship between human gut dysbiosis and disease, especially diseases of inflammation. Not only does dysbiosis of the gut microbiome lead to certain diseases, certain diseases also alter the gut microbiome. Recent findings have illustrated a role of microbiota dysbiosis in cardiovascular disease, irritable bowel disease, Clostridium difficile infection, and inflammatory bowel disease,1 as well as rheumatoid arthritis,3 colorectal cancer,4 obesity,5 and diabetes.6...
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Excerpt - >>> DR. BENNETT: One of the most important things about a drug side effect (potentially ?) is an animal model, and my thinking is that deep in the woodwork at Johnson & Johnson and at Bayer their animal model data exists and it says that when you gave mice this drug, they produced long-term and short-term neuropsychiatric illness, because you would not get a drug to market without animal testing. And what we did in 2014 and 2012 and ’13 is with Dr. Raja Fayad. We gave mice increasing doses of Cipro, which apparently – in the laboratory setting, and we generated the exact same side effects we talk about now, in the mice, which is a really clearly convincing argument that the mice are – that this is a toxic drug, and why – the basic path of physiology is – and we identified it in a second set of series that my son led, who is now at Oxford in pharmacology. We did a series where we got blood samples from 25 people with neuropsychiatric illness, with quinolones, and 55 percent had a genetic abnormality to cytochrome P450 gene, which led them to mis-metabolize, under-metabolize the drug, which means the reason why it’s causing these psychiatric effects is many people have a genetic defect that leads them to poorly metabolize the drug and leads to tremendously large CNS-brain accumulation of drug. And then when Raja did the work with the mice to generate the exact same symptomatology, he called me up on a Monday and he says Charlie, I have it, I’ve nailed it, it is “this.” I went to see the mice and they were depressed, they couldn’t – (inaudible) – they couldn’t go through a maze, and as increasing dosages we had neuro-psychiatrically damaged mice from Cipro. That was on a Monday. Thursday I got an email at the University of South Carolina where I worked, and there had been a murder on campus and Raja was dead with the papers – with his dead body lying over his research. And his wife and he had had a fight and she shot him eight times and killed herself. So I was able to get his research and it was published – that was completed three days before his untimely murder. <<<
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>>> Bitter Pills: Inside the Hazardous World of Legal Drugs Paperback – May 4, 1999
by Stephen Fried (Author)
We take our medicines on faith. We assume our doctors are well-informed, our drug companies scrupulous, our FDA diligent—and our medications safe. All too often we're wrong. Just how wrong is documented in this critically acclaimed portrait of the international pharmaceutical industry by one of our most highly respected investigative journalists.
According to the Journal of the American Medical Association (JAMA), adverse drug reactions are the fourth leading cause of death in America. Reactions to prescription and over-the-counter medications kill far more people annually than all illegal drug use combined.
Stephen Fried's wife took a pill for a minor infection—and ended up in the emergency room. Some drug reactions go away in a few hours or days. Diane's did not. This emotionally wrenching experience launched Fried into a five-year examination of the entire pharmaceutical industry, the most profitable legal business in the world. Rigorously documented, Bitter Pills is a full-scale portrait of pill making and pill taking in America today, presented through the powerful human drama of doctors, patients, drug companies, the FDA, and government regulators as they war for control of our medicine cabinet
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https://www.amazon.com/Bitter-Pills-Inside-Hazardous-World/dp/055337852X
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Cipro -- Fluoroquinolone associated disability -
>>> “The Cost of Being a David,” a conversation with Dr. Charles Bennett
https://www.knowrisks.org/episode6
On this episode Dr. Charles Bennett joins Heather and Lee to discuss the forthcoming book, Taking On Big Pharma: Dr. Bennett’s Battle; black box warnings; citizens petitions; and his recent journal article, “Davids versus Goliaths,” where he talks about his story and that of 26 others and how they were retaliated against for reporting on drug safety, effectiveness, and data integrity concerns.
LEE: Awareness is power.
HEATHER: And it can save your life.
LEE: Welcome to our podcast, “Know Risks.”
HEATHER: I’m Heather.
LEE: And I’m Lee. We’re two moms, a lawyer and a nurse, who were brought together by a misfortune. Both our children were harmed by adverse drug reactions.
HEATHER: The purpose of this podcast is to educate people on the risk of any health treatments you put in or on your body.
LEE: We feel if we’d been properly informed and been our own experts, our children would not have been harmed.
HEATHER: In today’s world, with medicines being incentivized for profits, you need to educate yourself. Know the risk of health treatments and it can protect yourself and your loved ones from being harmed.
LEE: Thank you for joining us today on our episode, “The Cost of Being a David.” We are honored to have Dr. Charles Bennett with us to discuss his new book, Taking On Big Pharma, black box warnings, citizens petitions, and his publication, “Davids versus Goliaths,” where he talks about his story and that of 26 others and how they were retaliated against for reporting on drug safety, effectiveness, and data integrity concerns.
Here is Heather to tell us a little bit more about Dr. Charles Bennett.
HEATHER: Thanks, Lee.
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Dr. Charles Bennett, M.D., Ph.D., MPP
Charles L Bennett M.D., Ph.D., MPP, is the Frank P. and Josie M. Fletcher Chair, and the SmartState Chair and Director of the SmartState Center for Medication Safety and Efficacy at the University of South Carolina. Dr. Bennett was the first physician to hold the A.C. Buehler Chair of Economics and Medicine at the Northwestern University Kellogg School of Management and the Feinberg School of Medicine. He has led seven R01-funded research grants on pharmaceutical safety, with the initial decade funding the Research on Adverse Drug Events and Reports — also known as RADAR — at Northwestern University, and for the past six years, the R01 funding has supported the Southern Network on Adverse Reactions — also known as SONAR — at the University of South Carolina. The SONAR project includes active collaboration with clinicians and researchers throughout the United States, Europe, Canada, and Asia.
Dr. Bennett is an academic hematologist/oncologist who has been the principal investigator for over $15 million dollars in peer-reviewed grant support from the NIH, the American Cancer Society, and the Pfizer Foundation. Dr. Bennett is a Phi Beta Kappa and High Honors graduate of Swarthmore College (in 1977), a 1981 graduate of the University of Pennsylvania School of Medicine, and a 1989 recipient of a Ph.D. and Masters in Public Policy from the RAND Graduate School in Santa Monica, for which he received honors in social science research. He has published over 450 articles in peer-reviewed medical journals, including first-authored papers in the NEJM, JAMA, Lancet, Blood, and Journal of Clinical Oncology, and Lancet Oncology.
Dr. Bennett is currently the principal investigator of the American Cancer Society Institutional Research Grant at the University of South Carolina, which is now in its seventh year of funding. His current paper, “Davids and Goliaths: Scientists versus Pharma,” is published in The Journal of Scientific Practice and Integrity. He also has a book, Taking On Big Pharma: Dr. Charles Bennett's Battle, which will be out in January 2023. Dr. Bennett will touch on both of these most recent publications in our interview today.
LEE: Thank you so much. We are just honored to have you here with us today, Dr. Bennett. I know that you’ve had lots of contact with Heather but, for me, I’m just so pleased to finally put a face to the name, a name that helped me so much through my journey with my daughter, Charlie. The work that you have done on fluroquinolones has just been hugely instrumental in helping to get the black box warnings on that medication, that medication that just has such horrific side effects. And I know that as a community, survivors, fluoroquinolone survivors and loved ones of people harmed by fluoroquinolones, we almost consider you saint-like for the work that you’ve done and we just so greatly appreciate it.
I think it might be nice today if we could perhaps talk about these black box warnings. I know the fluoroquinolones have had several of them added over a period of years. And perhaps you could just walk us through that process, like what’s involved in trying to get those black box warning attached to these medications.
DR. BENNETT: Just to be clear, we tracked black box warnings, safety advisories, communications, side effects, adverse events. They have seven different sections on the label. And as Heather knows, very intimately, when you get to a package label, which is often attached to the product that you give to the pharmacy, you should set aside a couple days worth of reading time because the labels are – I’ve been up to places where they do product review for quality up in New York and Underwriters Laboratory and what they did was they printed one of the labels out in a font that you could actually see and the label went for 42 feet.
HEATHER: Oh, my gosh.
DR. BENNETT: Nobody could read it. And so, as you can imagine, the labels are primarily for lawyer protection. Heather, maybe you’ll agree with me –
HEATHER: Yes.
DR. BENNETT: – because Heather’s clearly a lawyer. And then they claim that it provides some insight into side effects of a drug and you would need to have a whole day worth of reading to do it. We have on the labels what used to be called black box warnings. The FDA, in their infinite wisdom, thought the color black was too sinister so they made them box warnings now; they took away the black box warnings because black box warnings – you could almost imagine somebody might want to read it. But a box warning, you can really get past and say there’s nothing different because the color’s not different. Box warning, by definition, to the FDA, is there’s no regulatory requirement of what gets you to a black box warning, so it’s sort of like they say at the Supreme Court, you know it when you get there, and there’s no – say if you have X, Y, Z, A, B, and C you’re in a black box. No such thing X, Y, and Z, A, B, C. The box warning is the hope that the patient who gets the label might read at least the box warning, which should have three to four major concerns, and that’s it. And that way they don’t have to read 57 pages in the warning and the four major concerns in the black box warning. So that’s what we’ve done over time. And in 2006 the box warning, black box at that time, was for Achilles’ tendon rupture, and I’ve known several people who have taken one or two doses of the quinolone – Cipro, Levaquin – and they end up with a bilateral or unilateral Achilles’ tendon rupture. Also shoulder rupture. You can rupture any tendon in the body. My lawyer came from his biopsy of his prostate where he got a dose of Cipro they said would be good to protect against infection, and then the parking lot at the place where he got it his biopsy, he fell down because both Achilles’ tendons ruptured about an hour after he took the biopsy.
Those black box warnings, 2006, weren’t easy to get black box. Ralph Nader’s group, which Sidney Wolfe led, helped petition and they were not – they being Johnson & Johnson and Cipro. FDA supported Johnson & Johnson/Cipro – (inaudible) – no black box. In the meantime, I had tried a clever idea that I had never thought about except for Richard Blumenthal, currently Senator Blumenthal of Connecticut. Then-attorney general of Connecticut said to me he liked one of my concerns on a different drug and wanted a black box warning on it and so he and I collaboratively – first collaborative black box warning from an attorney general. He was Connecticut attorney general at the time – on it, and we got a year later – one year later we got the first ever black box warning collaboratively from an attorney general and a public citizen, myself. And Sidney Wolfe read about that and he replicated that and attorney general of Illinois, Lisa Madigan, joined him and they got a black box warning for Cipro and Levaquin for Achilles’ tendon rupture. It did not come easy because they had to file a lawsuit in court – (inaudible). Besides the petition you had to do lawsuit in court. There have actually been only six citizen petitions ever accepted, in part or in total, by citizens. Citizen petitions, just to let you understand, are really misnamed because they’re meant to be competitive drug company petitions and they’re primarily there to make sure that competitors do not market the drug, and 95 to 98 percent of all citizen petitions are written by drug companies trying to prevent another drug company from competing against them. It’s very rare.
HEATHER: Wait, so the drug companies – just to understand this because this is just fascinating to me – so the drug companies are doing citizens petitions against competitor drugs?
DR. BENNETT: Right. And it would be primarily a generic drug and a branded drug. The branded drug will say the generic drug is not up to quality; it should not be allowed on the market, and regulation is generic drug companies being brought against by the brand. The courts have six months to adjudicate so it puts a six-month halt on a generic company from manufacturing and competing. So these become a huge game and a way to slow down your competitors. On the other hand, a poor citizen like me trying to write a citizen petition, they have no – there’s no law there. Only six of us have done it besides Ralph Nader, and two of the six that have ever been accepted, two of the six that have been submitted by people other than Ralph Nader are Sidney Wolfe. Two of the six are by me. And they both were partially accepted. I’ve had two rejections. But I have the most citizen petitions in the country that are partially accepted.
HEATHER: Excellent. And I know I was with you – I believe that was in 2016 for the citizens petition that you submitted in regard to the fluoroquinolone-associated disability. And just to back up, for some our listeners who are maybe just joining in, I know a lot of our listeners will see Dr. Bennet’s name and they know quite a bit about fluoroquinolones, either from being damaged by them or having a loved one hurt by them, but in this particular citizens petition, was that – that was one of the ones you’re referring to that was – resulted in a black box warning for the associated disability?
DR. BENNETT: So to bring things clearer, Linda Martin, who’s very active with me and Heather, has worked with me hand in hand on citizens petitions and we felt filing a petition just like a piece of paper over the transom would be unlikely to be successful and needed some more oomph. So Linda and I and Terry Aston, we flew in 2014 to Washington, D.C., to the Rayburn Building and we met with 19 senators, policymakers about a petition that we wanted to write in 2014, which we wanted them to include issues related to fluoroquinolone-associated disability, long-term neuropsychiatric disability. We had 19 senators; 18 of them kicked us out of the office with the boot. And one of them had – the aide to Patty Murray, he was very subtle, called Terry at home many nights after that saying that he was talking to Senator Patty Murray, liked our petition, was unlike the others, and lo and behold, in 2015, we had an FDA Advisory Committee meeting, which Heather attended, and the advisory committee meeting talked about fluoroquinolones. It had came as a shock to us – maybe not to Heather; maybe you were able to lobby for it, but we had no idea they were going to have that. But when we went to citizen petition review in 2015, November 5th at the FDA, there were many patients, many family members. There was an armed guard. There was a rope line. There was CNN, Wall Street Journal, New York Times, there were a bunch of lawyers, there were a bunch of investment bankers looking to see which way the stock went, and then – (inaudible) – was the fact that 21 advisers of the FDA and on two sides people in suits on the left side with the suits I can’t afford to buy; those are called – businesspeople at Johnson & Johnson and Bayer, and then on the right side was the FDA people, and at that meeting they discussed fluoroquinolone-associated disability and one FDA employee, Debra Boxwell, said that she had read through notes of people like Heather’s son and others; she had read about 80 of them; she felt that despite it not being statistically significant – which maybe David Healy might have addressed in his podcast – that she had never seen such visceral and such real pain at these narratives, which were never before used by the FDA to define an adverse event were in fact for her definitive. She called it FQAD. We left the meeting with a 21-1, 18-2 and 19-1 approval that all three uses – uses would be sinusitis, COPD, and also UTI – that quinolones should go first-line drug to last-line drug. We left that meeting with The Wall Street Journal supporting us, and as you can imagine, the next day nothing happened. It was an advisory committee meeting. They decided to disregard our advice – 19-2, 18-1, 20-1. Nothing happened. A year later, Johnson & Johnson and Cipro said that they had reconsidered their thinking and these drugs were now last-line drugs in 2016. 2018, I get a letter in my office in a brown envelope, no FedEx, no nothing. I open it up; it’s from FDA, at that time Janet Woodcock, the interim director of the FDA, and she said she thought that the suggestions that I made in 2014 she could live with for half of them, and the black box warning became a reality in 2018. So to remind you of the timeline, it was not a year; it’s four years – (inaudible).
LEE: That’s just terrible when you – well, Heather and I both know how many people’s lives have been affected by this category of medications and to just know how much effort and convincing it takes, and then the time, so in that time, how many other people have been harmed? And then you brought up – and Dr. Healy did touch on – that it’s only a very small percentage – I think it’s 1 percent of the people that actually the adverse drug reactions get reported. Is that right?
DR. BENNETT: We published in different journals that we could empirically document only 1 percent get reported because we had a way of getting two sources of documents – what was reported and, secondly, what was reported in clinical trials, and we showed only 1 percent were ever reported. In 2019, after we were frustrated that the black box warning did not actually have the effect of actually warning anybody about the side effect, I filed my third citizens petition related to the quinolones and this time I asked if there could be a signature required by patients and doctors before they received the drug, going through the side effects that people like you, both of you, who have experienced these side effects would know about them in real time because you’d signed a consent form and your doctor signed the consent form and the pharmacy signed the consent form, which is not unusual – it’s severe but not unusual; it’s done for retinal gas. It is done for acne drugs. I mean, you can’t imagine. They also do it for drugs they use for anemia, for cancer patients. And we’re just asking to have some really strong way to make sure that you don’t bypass something that might come back to really affect lives, your daughter and her son.
LEE: Yeah, I think what that – well, what you’re asking for is really documentation of informed consent.
DR. BENNETT: Exactly. And if you don’t document it, don’t get the drug. And we got a letter, a terse letter back in six months from the FDA saying this will never happen in my lifetime.
LEE: Wow.
HEATHER: Now, can we – yeah, I’m just still kind of – I just want to go back for a second because you said it was two – the black box warning label for the FQAD actually was done because the two pharmaceutical makers, Johnson & Johnson being one of them, two years later they decided that was important? What would have been the motivation behind that in 2018?
DR. BENNETT: I think what happened (beyond ?) that is to have an advisory committee meet, make a recommendation, and nothing happened, it must mean there must be ongoing, behind-the-scenes conversations between the FDA and the company, and finally they convinced them that this is the right thing to do. So there’s no real event. But I will say, it was interesting that we found in 2015, you had in 2014 – the meeting was held in 2015. And the other important event was in 2018; the European Medical Association asked me and asked others and they flew patients in from 27 European Union countries and each of them talked about their own personal experience with fluoroquinolone-associated disability. Now, the FDA and every country in the world has refused to call it fluoroquinolone-associated disability. The term that they’ve used is called long-term disability or long-term neuropsychiatric disability. They do not call it fluoroquinolone-associated disability because I don’t think they want another name to be used in the ICD-10 nomenclature and the name would require possibly (meaning ?) that there will be money. Fluoroquinolone-associated disability might mean that there should be a claim for disability –
HEATHER: Correct.
DR. BENNETT: – from the government and you would be entitled to some disability payments. So they have purposely not gone with it. But the Europeans voted 28-0 – 27 now because of Brexit – that what we had found in the U.S. was exactly correct and they also moved it from first-line to last-line in Europe, and that also may have been somewhat of a trigger for the change because the Europeans were moving on it. Japan followed, Australia followed, New Zealand followed, and Canada followed. Those four countries I just mentioned at the end did not change placement of the quinolones from first-line to third-line; they just made an announcement that these drugs to them were too important to move around and that people could occasionally – and they wrote rarely – have permanent neuropsychiatric damage. They were uniquely different from the 28/27 European Union and the U.S. in terms of that. The Japanese, for instance, said that they only saw it with Levaquin in only one or two cases so they really wouldn’t even put much on their label about it, and only on Levaquin and not all quinolones.
LEE: But one would think potentially that the motivation of Johnson & Johnson to want to help change the labeling could be the – were they under a lot of legal, like, lawsuits as well?
DR. BENNETT: Lawsuits do not work in this case because the Supreme Court has, in its infinite wisdom, ruled in the Atkins case in 2013 that if a drug is generic the manufacturer cannot be sued for anything, and so if you take generic Levaquin or generic Cipro and had a terrible outcome like Heather’s son or your daughter being ill, none of that can be sued by anybody. So the reason – put on a label is not because of anything related to lawsuits; it is about just trying to get the label to be complete.
LEE: Well, yeah, and subsequently prevent people from being harmed because it’s, you know, the health care professionals should be aware –
DR. BENNETT: I think that in the perfect world they’d be aware. The reason why I filed the last petition is because I don’t think they are aware and that’s why I asked for the consent form. I don’t think – and I have many, many friends who tell me routinely, I’ve used Cipro and Levaquin for at least three decades. Now, don’t forget these drugs came to market in 1986 and the only one who started raising concern besides concerned patients and family members was me in 2011 and (Jay Cohen?) who died in 2011. And so this concern lasted 11 and 14, 25 years before some initial concern happens, and after 25 years the label gets changed, in 2018 with the black box warning, which is 14, 18 – 32 years after these drugs hit the market.
HEATHER: Yeah, and, I mean, we know how many people were harmed. I believe – who was the journalist – I think that was in the late ’90s – Stephen Fried, who wrote Bitter Pills. I mean, that was almost identical situation what happened to his wife, although she survived, and my son. You know, having the neuropsychiatric issues, being diagnosed with bipolar, landing in the mental health system. So, I mean, essentially, it just sounds like, to me, that for the industry, anyways, and for our regulatory agencies, it’s just not really about patient safety but more about navigating a system to kind of slow down any type of negativity associated with the drug. In the meantime, the pharmaceutical industry is just reaping the profits from it. I mean, is that kind of what’s happening here?
DR. BENNETT: I don’t think so, actually.
HEATHER: No?
DR. BENNETT: I think what’s happened since Stephen Fried’s case, his wife was very sick and mentally ill for a year, and he wrote a long book, as you – (inaudible) – Bitter Pills. Now if you talk to Stephen Fried, he hardly brings it up in a conversation.
HEATHER: Really?
DR. BENNETT: Yes. So Heather, you know – and you, Lee – you’re committed, long-time, lifetime advocates. You’ll be there. Stephen Fried, you call him up, he’s writing a different book now. He’s moved on in his life. His wife is a little better, a lot better, and this is all a bump in the road that he hardly remembers.
Now, I would like to say that, make it clear that this is not a rare side effect.
HEATHER: Exactly.
DR. BENNETT: People blow us off all the time and say it’s a rare side effect. And the reason why they do that is because a side effect that causes a heart attack or Achilles’ tendon rupture, it’s easy to see and feel. Tendon goes out, you get tendon repair; your heart attack goes out, you go to the hospital. But when you get a brain attack or brain injury, then they talk to you about drinking too much, having poor sex life, not accommodating, and millions of things, and it does not include – and this is why – that’s why almost the majority of these actual events occur in isolation. You’ll go see at least 10 doctors who would tell you that everything that has happened is in your mind, it can’t be this drug that’s been on the market since 1986 or we would have heard more about it. And it’s true.
HEATHER: Yeah, exactly. And, you know, to kind of go along with that, I mean, in my son’s case, you had a patient who was telling his doctors, even though he was experiencing these neuropsychiatric issues, that this is from this drug, this is from this – he’s, you know, connecting it, and again, none of the many, many doctors, you know, wanted to give any validity to that. And I think that that’s kind of a good lead-in because the system really has a way of shutting down these type of complaints from patients or giving them the attention that they need. And I know you have an article that will be published soon in The Journal of Scientific Practice and Integrity that kind of deals with – we talked a little bit about the low number of reports, such as FAERS reports, the FDA Adverse Event Reporting System, from doctors and also from patients. You can’t really, you know, criticize a patient for not knowing to report because it’s hard to know that information and if you’re scared and you’re having a bad reaction to a drug, especially one that might affect your perception and your ability to function and your mind, more likely than not, that’s not going to happen. And we don’t have a lot of doctors reporting either for exactly the issues that you just discussed, Dr. Bennett. But I kind of want to go back because I know Dr. Healy, I know you have been a victim of this, and it’s just this total maligning of anyone especially in the medical field or scientists who come out and speak about – you know, advocate for the patients or try to warn about potential effects of drugs. I just was wondering if you could talk a little bit about that.
DR. BENNETT: One of the most important things about a drug side effect (potentially ?) is an animal model, and my thinking is that deep in the woodwork at Johnson & Johnson and at Bayer their animal model data exists and it says that when you gave mice this drug, they produced long-term and short-term neuropsychiatric illness, because you would not get a drug to market without animal testing. And what we did in 2014 and 2012 and ’13 is with Dr. Raja Fayad. We gave mice increasing doses of Cipro, which apparently – in the laboratory setting, and we generated the exact same side effects we talk about now, in the mice, which is a really clearly convincing argument that the mice are – that this is a toxic drug, and why – the basic path of physiology is – and we identified it in a second set of series that my son led, who is now at Oxford in pharmacology. We did a series where we got blood samples from 25 people with neuropsychiatric illness, with quinolones, and 55 percent had a genetic abnormality to cytochrome P450 gene, which led them to mis-metabolize, under-metabolize the drug, which means the reason why it’s causing these psychiatric effects is many people have a genetic defect that leads them to poorly metabolize the drug and leads to tremendously large CNS-brain accumulation of drug. And then when Raja did the work with the mice to generate the exact same symptomatology, he called me up on a Monday and he says Charlie, I have it, I’ve nailed it, it is “this.” I went to see the mice and they were depressed, they couldn’t – (inaudible) – they couldn’t go through a maze, and as increasing dosages we had neuro-psychiatrically damaged mice from Cipro. That was on a Monday. Thursday I got an email at the University of South Carolina where I worked, and there had been a murder on campus and Raja was dead with the papers – with his dead body lying over his research. And his wife and he had had a fight and she shot him eight times and killed herself. So I was able to get his research and it was published – that was completed three days before his untimely murder.
HEATHER: Oh, my goodness.
DR. BENNETT: And so I call the work that I do Raja’s legacy –
HEATHER: Yes.
DR. BENNETT: – because he had just gotten tenure as an academic, and this was the first tenured project. He had just received tenure at 42 and then he was dead. And so I felt – the work that he would have continued to do with me on the Cipro, we would have just continued to find more and more, but because of his untimely murder, we had to shorten it. And then the – (I guess ?) the other effects that I said – besides Raja, my son’s findings on the genetics were stark, startling. We filed a provisional patent on that genetic test, and with some additional help we hope some day to market that test so before you take Cipro or Levaquin you take the gene test and if your genes aren’t going to metabolize the drug, they’re going to end up with a CNS (blast ?). Don’t take the drug.
LEE: Well, we’re not researchers but just through the journey with my daughter, you know, we’ve connected with thousands and thousands of people that have been harmed, and there is a commonality in that a lot of them seem to have what they call this – where they don’t methylate or they don’t detox. But the research that you’re saying, which, you know, is not, whatever, published or – but do you feel that it’s specific to the fluoroquinolones or that’s already sort of a harmful enough drug that that’s one of the ones that makes it worse? Would other medications be a factor with this genetic –
DR. BENNETT: There are – (inaudible) – drugs that have cytochrome P450 metabolic issues and this is just one of many.
LEE: OK.
DR. BENNETT: But what it accounts for is the fact that this side effect is undoubtedly not rare. The cytochrome P450, out of 25 people we tested, or 54, we had 55 percent with the genetic – (inaudible). So the reason why people are not being protected is not because this is rare but because doctors won’t listen to it and won’t report it and won’t say anything about it and won’t count this. So we 100 percent believe this is a fairly common side effect, and if you walk around the world and talk to people you meet socially on the plane or at a restaurant or anywhere else, they say, this happened to me, happened to my aunt, my grandma, my mother, my brother.
LEE: I agree and I think, too, that part of the problem is – well, the doctors aren’t aware of the warnings, they don’t listen to you when you complain because one of the things that I heard – we must have seen over 12 different doctors. They thought well, the drug’s out of the system so it wouldn’t keep causing harm. It is a little bit of a delay and these symptoms can keep developing. And then it’s given – a lot of the time, people are elderly, so if you have – you know, they just categorize you, oh, you’re, you know, feeling depressed; you know, they’re associating it with age a lot of the time or just –
DR. BENNETT: But as you know, from your own personal experience with your daughter, and Heather knows from prior experience with her son, there’s nothing about this that is protected by age.
LEE: No.
DR. BENNETT: Young people – at the FDA meeting, Heather, that you were at, the 17-year-old girl from Seattle, Washington, came in a wheelchair; she’d found her way to Harvard before she took this drug for a bladder infection and she wasn’t going to Harvard. She was going down a wheelchair to the FDA.
LEE: Yeah. And I think that’s why we were – our cases were successful in that we had – like, they told me, my daughter was a high-level athlete in perfect health and then within 10, you know, 10 days, she could barely move her arms, like, and had all these issues, which I didn’t even realize the anxiety and all those other things were actually related until afterwards when those warnings came out, thanks to you. I didn’t even connect those ones, but it was because she was so young and healthy that it was like textbook, almost.
DR. BENNETT: I’d like – you mentioned in your preamble in that conversation that Heather and you were successful for a reason. Could you define to me and to the audience what you mean by successful?
HEATHER: Well, that’s interesting – (laughs) – because what’s successful, you know, you think you’re – when something like this happens to you in your family, your first inclination is to try to, you know, get the word out. First of all, you’re – in my case, I’m mourning the loss of a child and also not wanting this to happen to someone else. In terms of success, I would term success in this in having broad knowledge amongst patients of the dangers of these drugs, which, you know, signed informed consent? Yes. That’s extremely important. In terms of court cases, I think Lee and I can both attest: It’s a long process and you think in doing so you’re trying to achieve some type of acknowledgment for the wrong that’s been done either by a doctor or by the pharmaceutical industry, but the result of those, if it’s with the pharmaceutical industry, is going to be a settlement with a nondisclosure, or a gag order, so the goal of talking about it’s not really going to happen. And even in a basic law case, it’s just not – the courts aren’t suited to make the type of broad change that’s needed in this. So when you speak about success, it’s just – it becomes very frustrating as you start to move forward down these different paths of what you think are your recourse for the type of damage that’s done to people, you know, only to find out that the impact of what you’re doing is very small. And I think that’s what you’re getting at, Dr. Bennett. Is that correct?
LEE: I think so too. I’d just add to that before he answers is that that’s a really great – that made me think, just right on the spot, I actually don’t think that we were successful and I think that’s one of the reasons for our podcast is that our individual kids’ cases were not about trying to get financial compensation. You could put no money on – I’d give up everything I had to go backwards in time and not have that happen, and I know Heather would give probably 10 times that. So we got acknowledgment, which you seem to want after being told over and over and over that this is in your head, that this isn’t happening. So that I felt successful in. But in getting a broad audience reached, we’re hoping to do more with the podcast. But obviously the work that you’ve done trying to get some labeling, and hopefully that there will be this one where they have to actually sign, that’s going to make way more of a difference because it’s going to reach way more people.
DR. BENNETT: Well, my citizens petition is out there in the web and anybody who wants to sign on to it, you just sign on to it through the website and people put a note supporting it. You can talk to – Heather knows some political people in her neighborhood. You can chat those people up and try to get – (inaudible) – the more political agenda you have, the more political influence you have, the more likely it is to happen. Bart Stupak, who used to be a congressman from Michigan, his son died of Accutane-induced suicide. He put the black box warning and the patient consent on Accutane. He’d be all over trying to get this for a similar story.
I will make a mention to this and I haven’t given you my journey in full. I have two pieces – three pieces of information to provide you. Besides the article coming out, my – a biography of me has been accepted and will be published – distributed by Simon & Schuster.
HEATHER: Oh, congratulations.
DR. BENNETT: And so a lawyer who went to Harvard Law School, taught at Yale and Stanford, University of Chicago, University of Texas, 93 years old, has spent six years detailing my journey with the Cipro and Levaquin, and they also added another journey that we did on Epo, a drug that’s used for anemia made by the largest biotech company. When Epo came up, in 2006, the result was the University of Northwestern, where I worked for 24 years as a stellar researcher with the most grants, resulted in them saying that I stole my research, I stole my money, I created no new research, and they took all my grants and gave them to people that did not do the research. They took my academic position away and I have been unable to return to a (pharmacy ?) medical school for 13 – since 2008. It’s now 15 years that I’m unable to get a job at a medical school, which I’ve applied for almost every year and sometimes twice, three times a year. And the important thing about that is they have a note on the internet you can read yourself, by Mort Schapiro at Northwestern, saying that, in his opinion, as the president of the university and the provost, dean of the medical school, Charlie Bennett is an unfit researcher and has developed and has propagated research that is not replicable and stolen money in the meanwhile. And that letter, which is on the internet today, this minute, is still there and I’ve never had a meeting in my life with Schapiro or Linzer or the dean, Neilson, in my life. But they did say – and I heard this from somebody else – is that somebody who knew the inside of the case was told by the university if he could sign a sheet that said that I was all those things the university could blame all their troubles on their mismanagement of my grants on me and I would pay the university’s $2.9 million fine. The end is they were able to give me a $475,000 fine on my “mismanagement,” quote/unquote, of grants, which I don’t manage because I’m a researcher, not a grant administrator, and I paid the $475,000, which required me to sell my house, empty out my retirement accounts, and as part of that – shortly after that, two, three years later, they took away all my research grants, gave them away to people who don’t know how to do the research. Research became pro-pharma. They took it from anti-pharma pharma oversight to a pharma booster, and that research then dissolved, and then they tried to take my medical license away and said that I could not practice medicine, (collected ?) $50,000 (to get ?) the license away. And the university just last week had Sidley Austin, a rather large law firm – said that while the note about me is not – is meant to be harmful that unless they can find a fault in it, it’s a lie, it needs to stay up there for the rest of the life of the world and no reason to take it out because history is history. And they make a point in the letter that no employee at Northwestern currently – when they wrote the letter in 2013 – had ever mismanaged my grants. Well, I left in 2010 and the woman that mismanaged my grants in 2009 was fined, criminal fine, sentenced to jail, quit her job for cause, and paid a penalty, and the reason why in 2013 she wasn’t considered a current employee four years after I left is because she wasn’t a current employee; they fired her four years ago. And so it shows you, at the end of the day, they would not – and they will not – this letter is used by every medical center that I’ve applied to, by their lawyers, for reason not to allow me to work as an oncologist in the medical school where I have spent 14 years of training and 20 years of research to do my work.
The only good side, the silver lining of that, is because of that effort I moved to South Carolina with a brand new slate because I lost all my research. I went to an FDA meeting in 2011. At that meeting I met (John ?) Bradee (ph) who has a very severe case of quinolone-associated neuropsychiatric damage, and it was because I met him at that meeting, shook his hand, listened to him, that I spent the next 10 years of my life on Cipro- and Levaquin-associated disability.
LEE: It’s a hard journey and tragic, but, I mean, us quinolone-affected –
HEATHER: We’re grateful. (Laughs.)
LEE: We’re grateful, not that that’s any consolation for what you had to go through.
DR. BENNETT: And we’re not done. As Heather knows, I’ve filed a whistleblower lawsuit personally against Johnson & Johnson and Bayer, saying what they’ve done is not (disseminate ?) the safety issues, and we’ve gone – we’re in the public domain now. It’s in the public domain; you can just google it. But we’re in a very positive stream of decisions. Judge Salas, who’s the judge in New Jersey whose son was shot by the FedEx driver and then her husband was shot by the FedEx driver but not killed, son was killed, and she is our judge – (federal ?) court – and we are publicly out there, and if the decisions continue to go our way, it will be a $2 billion payment from Johnson & Johnson related to the the side effect.
LEE: So we’re going put some of – just for our listeners, we’re going to have – you mentioned at the FDA there’s somewhere that they can go to – can you just –
DR. BENNETT: They can do it on the FDA website. There’s a citizen petition website where you can sign up. But they should also – and Heather knows this – they can talk to their local political people. And they can read my citizens petition; it’s also on the website. And I’ve had two congressmen from St. Louis, Missouri, both Republicans, in this case, support me, and the more political support we can get for those petitions to require the consent, the more likely they will actually be enacted. So you go to the website, you can sign your name up and say you agree with the petition, but you can really talk to your congressman and say it’s – I have a personal reason why this must be so; it’s my son and my daughter that I believe in personally, are important to me, as you know – Heather with a lost son and you, Lee, with a damaged daughter. There’s a reason to be there. And your congressman is only meant to help you and that’s why I think going through congressmen would be something terrifically important.
HEATHER: And this whole – like, the retaliation that was taken against you, Dr. Bennett – I mean, I briefly mentioned an article that will soon be published by you; it will be published by the time we air this podcast – but this is common. I mean, this is just common for –
DR. BENNETT: No, let me clarify this.
HEATHER: Yeah.
DR. BENNETT: No, I’m not saying it’s common.
HEATHER: No?
DR. BENNETT: I want to talk to you about icebergs. Some people ask me if this is the tip of the iceberg. What do you think? Is this the tip of the iceberg? Heather, what do you think?
HEATHER: A very small tip, I would say. (Laughs.)
DR. BENNETT: OK, I’m going to tell you this is the iceberg.
HEATHER: This is the iceberg?
DR. BENNETT: This is the iceberg. And why do I mean that? In my paper, we have 26 Davids and Goliaths. The paper’s called Davids and Goliaths. If you look on Google under Davids and Goliaths, you’ll see a total of zero articles called Davids and Goliaths. You’ll see a thousand called David and Goliath, because Erin Brockovich, she’s a David, the guy from the Insider was a David. People are Davids. Like David Healy is a David. The 26 Davids are never in one paper. Everybody fights a very lonesome fight where they get slaughtered by the company and by the university and, in my case, the Department of Justice on top of it.
HEATHER: Yeah, unbelievable.
DR. BENNETT: You know, to fight the university was hard, but I could get through it. To fight the drug company was hard but I realized I would get through it. The Department of Justice Assistant U.S. Attorney Kurt Lindland said to me in 2013, he goes, Charlie, let me just tell you the three most evil people in Chicago ever: those are Rob Blagojevich, the governor who was in jail; Scooter Libby, who worked for Ronald Reagan, was in jail; and Charlie Bennett. And he said, I will do everything in my power to make sure all three of those people go to jail. Can you imagine that? And then he wrote, he said, you know, I’m going to write a press release about you, it’s going to cost you your job, and I don’t have to be accurate; nobody vets my press releases. And so he wrote one parallel to the Northwestern one where he talked about nobody at the university was involved because the woman who was involved had been fired because she was in jail. Surely she was not employed by Northwestern when she was in jail. And he said I can say anything I want and I will have your career in three months’ time and you’ll be broke and I can take your family’s incomes too, so there’ll be nothing left for you. He said, you will learn what it’s like to work for Starbucks.
LEE: Wow. Oh, my god.
DR. BENNETT: Can you imagine getting that from the Department of Justice?
LEE: No.
DR. BENNETT: When all you’re doing is research. As my old boss said, I’ve saved more lives in American medicine than anybody ever in the history of the United States. People can save lives by generating new drugs. (Inaudible.) The amount of lives I’ve saved on safety is at least millions of lives, and more than anybody would do on 50 drugs like Cipro and Levaquin. As my mother said to me before she died three years ago, she said, they will kill you, but when they do kill you, you won’t know who did it. So the 26 Davids in my paper, the reason why I say, Heather, it’s not the tip of the iceberg, of the 26 people – and I personally interviewed almost all of them, went all over the country and the world to visit with them; I sat down with them; we had lunch. Many of them had hidden these stories inside their bodies, inside their heart, inside their heads for decades because the pain of losing their job and the fight they had was so real that they never wanted to talk about it again. And I’m coming in there bringing it up again and everyone I have in my paper on Davids and Goliaths is named. The 26 Davids are named in my paper. And more than that, I have a quote from each of them in their own words that have been published in Senate hearings, FDA hearings, New York Times, “60 Minutes,” in their own words about the pain that they went through. So I didn’t ask them to tell me something. I just looked through this published literature for the words that they’ve used to describe their own personal experiences. So when I cited the paper, I said, you want to find the words? I give you the actual page number of the Senate testimony. Let me give you an example of one piece of words. Tyrone Hayes, who’s been in the New Yorker magazine, had a very tremendous negative experience at UC Berkeley. Graduated from Harvard undergrad, Berkeley Ph.D., chairman of the department. His department is on animal biology. And he found that when you gave frogs a pesticide, the male frogs became feminized, much to the disappointment of Monsanto – Syngenta at that time. And they – as he presented his talk – (inaudible) – at a lecture, Syngenta vice president said Tyrone, we knew – Tyrone’s an African-American chap, about 5’3”, his wife’s Korean or Asian – guy said to Tyrone, he says, you’re going to give a very important talk and you should say what you believe. He says, I just want you to know that we’re not above murdering people; we’re not above raping your wife; we’re not above lynching your kids. And Tyrone said to the guy, his name is in the book, my book, he said to him, that is the most disgusting thing I’ve ever heard in my life but fortunately I have my tape recorder on. And he has that on and he’s presented that around the world and he has that tape – that’s a real tape. (Inaudible) – to do that. Tyrone – they have an internet site called Tyrone Hayes, which is owned by Syngenta, calls him a pedophile, and when you go look up at Google “Tyrone Hayes,” you find the most mean things about Tyrone Hayes that the drug companies populated with inaccuracies, terrible things about Tyrone. A hundred counties sued Syngenta for the water was poisoned and hundred counties were fined or settled for $100 million the amount of money it takes to clean that water up and the damage it’s doing to the kids in those neighborhoods. That’s just one of the other 26 of me. Every story is as powerful as that.
We monetize – what does these 26 stories mean? The 26 stories – here’s the thing we found. This is even worse besides the stories. All those companies, they were eventually asked to pay criminal fines or settle civil lawsuits. The total amount of money involved in those lawsuits was $27 billion so that’s why I say it’s not the tip of the iceberg because if it were – the tip of the iceberg is 1 percent. That would mean that would be $2.7 trillion involved in this kind of work, which would be far more than COVID. We wouldn’t even talk about COVID today if this were $2.7 trillion. We showed a million lives lost from these drugs from the harm that they did, either very severely damaged or dead. We also showed 13 of the companies that we evaluated of the 26 – 27 companies evaluated, 26 people – 13 of them, when they were identified by the Davids as submitting fraudulent data to the FDA for approval, 13 of them submitted fraudulent data to the FDA for approval and the Davids in our stories pointed that out. When they pointed it out, the Davids lost their jobs and the FDA data went through and the drugs got approved. So the answer to what happened there is the messenger lost their jobs. The people who were actual culprits got these drugs through the FDA and sold – total sales of these drugs are trillions of dollars we’re talking about here. And we asked in the paper, in the conclusion, that the just answer for this work should be not destroy 26 people like me who have been unable to work for several decades, and I’ve gone through the best medical school, college, graduate school, Ph.D. programs in the country and I’ve been sidelined except for the quinolones for the last 15 years and I don’t see patients for the last two years. And I went to – I didn’t go to average schools; I went to Penn, I went to – I work at Johns Hopkins now, I went to UCLA, I went to University of Chicago, I went to Duke University, Northwestern University. We’re talking about schools – Swarthmore College – that you could never imagine anybody getting into all five or six of those schools ever in their lifetime, and to have that kind of training and that kind of education not being put to use –
LEE: It’s a tragedy.
DR. BENNETT: It’s a crime.
HEATHER: It’s criminal. It’s criminal. There should be charges against all of them. And, I mean, just the 26 – how many – I mean, scientists, doctors like you are few and far between of what we’re seeing now. We see that more than ever now with this recent pandemic is most are just going to go along with the program; they’re not going to speak up. And how many lives are lost there?
DR. BENNETT: You wouldn’t want to lose your job, your career, your reputation, your friends. How many of my friends have deserted me? I can’t even go see 99 percent of my friends. The job getting pushed away from me, losing my house, my retirement plan. Every time my son goes to school, when he was in high school, looks up the internet; all they have is a Department of Justice press release about me. He said, dad, I didn’t know you were a criminal.
HEATHER: Amazing. Well, if it’s any consolation, you know, the result of the system that silences those who have integrity and have a commitment to science and speaking out, I mean, this system – there’s so much blood on its hands. I am not the only one – I lost a child. I mean, my son should be here today, but for, you know, the refusal to speak out on behalf of a whole lot of people – certainly not you, Dr. Bennett. But it’s just – it’s horrific what you have to go through for doing what is the right thing, what is the human thing. I mean, the result of this system is families like mine, you know? A bright young man who lost his life over this, you know, for profits. So it seems to me at the very core of this is they just want to preserve the income and the money, and paying off a few people is probably just chump change for a lot of, you know, those in the industry. But it’s just so difficult to wrap your head around such an unconscionable system. I mean, just the violence of the health care system and medicine system itself – it’s – you know, I commend you and I know Lee does too, but it’s just so sickening to hear this.
DR. BENNETT: You know, the point is there is no way forward for somebody to follow behind me. I can’t, in good faith, tell my son, I hope you save as many lives as I did and I hope you don’t mind being put out of work before you ever complete your life mission and I hope you don’t mind losing all your friends and your house, part of your medical license and all your grants and everything you worked for. If you’re willing to give all that up to save people’s lives, then go at it. There’s nobody in their right mind who will follow behind me.
HEATHER: I pray there are people who will. (Laughs.) I pray there are.
LEE: If we lose all the Davids because of the way that they’re treated and destroying your life, just to speak up and do the right thing, then where does that leave all of the public and the safety? Like, it’s a really, really scary thing to think about.
DR. BENNETT: That’s why my current lawsuit is important and it has to be won. If that lawsuit is won, Johnson & Johnson will pay $2 billion. And that would provide an opportunity for young Davids to see a path forward.
LEE: Yes.
DR. BENNETT: I’ll be the first ever in the history of the United States to take my research, which started in 2011, file it as a false claims lawsuit with the government. I’ve been certified by the court as the finder and relater, the person with unique non-public information, so other people who can do research, who want to do research do what I do which is I file my work, I do citizens petitions, I filed the Qui Tam lawsuits, and that is a whole package of things that are nontraditional. Nobody files – (inaudible). I did. Nobody files a whistleblower lawsuit. I did. I’ve been certified that way. In a year and half or two, before the next presidential election, it is our goal and our hope that that money would come forward and then people who want to do the right thing may have spent a lot of years suffering, but at the end of the day, $300 million, $600 million comes back to us, there will at least be some financial gain for the work that’s happened. The book is very important for my effort as well. I hope it’s called Resilience, because that’s what it is. We have been talking with Hollywood producers. Al Ruddy, who just did the movie – 50-year anniversary of “The Godfather,” which he and Francis Ford Coppola got the Academy Award for, has done a 10-part series on how he made “The Godfather.” He’s 93 as well and he wants to co-produce my movie about this work. We have a singer, Carol Connors, who got the Academy – not the Academy Award – she wrote the song for “Rocky,” “Up and Away” (sic/”Gonna Fly Now”). She did not get the Academy Award because Barbra Streisand won the award that year for “The Way We Were,” 1977, the year that Elvis Presley died. But that song is by far the most downloaded song on any song ever from a movie, and she’s agreed, in person when I’ve seen her, to make my movie. So we feel that between the book, the movie, the court case, citizens petition, some of the work that you’ll follow on, people like that, this will be an enterprise. If you all take a chance to look at on Hulu TV, there’s a TV show called “The Resident” you may or may not have seen. It’s “The Resident.” On Hulu you can buy it for a buck or two bucks. It’s made by Amy Holden Jones, who’s a partner of Martin Scorsese. It’s been on Fox for seven years, but Season 3, Episode 7 is called “Woman Down,” Season 3, Episode 10 is called “The Whistleblower,” and both episodes are about my work, so we’ve been able to get it into Fox TV, we hope the movie, the book. So I – as Heather knows, you can’t just take one avenue; you’ve got to take multiple avenues and you have to be persistent. I don’t sleep ever. This is something I believe in day or night – and night. Tim Robbins is going to play me, just to let you know, 6 foot 2 –
LEE: Oh, wow.
HEATHER: (Laughs.) Oh, gosh, that would be just spectacular.
DR. BENNETT: His hair is a little bit neater than my hair.
HEATHER: (Laughs.) That would be spectacular.
I am just – Dr. Bennett, you’re so impressive. And no, I know that you’ve had to go through quite a bit over the past decade, longer than that. But it’s people like you who give us the energy to push forward in doing the small parts that we are and trying to address these issues.
LEE: You have been instrumental. Our children were harmed. Heather did lose her son but my daughter is here today because of those warnings, because if I did not have those black box warnings and just the information and the petitions that you guys did at the FDA, I would have no credibility and I would not – her symptoms, everything – we would have been down a completely different path.
DR. BENNETT: Let me say this: I got a call from a husband from Tampa maybe five months ago. His wife, she had no prior medical, psychiatric history. She had, like, a sinus infection or a pulmonary infection. Her internist gave her Cipro; she took the first dose and she felt foggy. She looked at the package insert; it says on page one it can cause CNS toxicity. She wondered to herself, what does CNS toxicity mean? He says, if you want to learn about it, go to page 42 of the 72-page – I think, Heather, you’ve already done it – going deeper on this. And then it says, some people have committed suicide after one or two doses. She took a screenshot of those statements and sent it to her doctor, her internist. He told her not to worry because it’s overblown. She tied herself to a chair in a swimming pool area in Tampa, she moved the chair into the swimming pool; when her husband came home from the store she was under water and she was dead.
HEATHER: Yep.
DR. BENNETT: And that’s only one dose.
HEATHER: And no history, no mental health history –
DR. BENNETT: No history.
HEATHER: – no history of depression.
DR. BENNETT: As with Heather’s son, they’re not talking about immediate – that’s only like this.
HEATHER: No.
DR. BENNETT: People can get psychiatrically damaged over months and then they throw you on a bunch of different psychiatric medications which can only damage you even more –
HEATHER: Yes.
DR. BENNETT: – and then months later the person can be dead. So we’re not talking about just immediate death.
HEATHER: It was a very slow walk with Shea. He knew – he connected the dots but it was a slow walk. And, you know, ironically he was put on more drugs by Johnson & Johnson, more drugs that are similarly as dangerous, Risperdal, which resulted in numerous lawsuits. It’s just this slow unraveling in a perfect storm of destructive treatments when you’re already experiencing a toxic reaction to another drug.
So this has just been a wonderful interview, Dr. Bennett. I appreciate you so much. I want to highlight this article again, and we’ll have it – a link to it on our website. It’s “Davids and Goliaths: Scientists vs. Pharma.” It’s going to be in The Journal of Scientific Practice and Integrity. Just so appreciative. We’ll get that petition going for you, most definitely, for all that you’ve done for all of us and all the victims out there. We surely want to support you and let you know we appreciate you, and your work has been lifesaving for many people, and life-changing for others. I know for me I can’t bring my son back. The result of this system and the result of the incentivizing treatments and prioritizing profits, you know, results in death. That is the result.
DR. BENNETT: Instead of destroying the messenger, we want the corporate executives who do this fraudulent work to end up in jail.
HEATHER: To be accountable. Yeah.
DR. BENNETT: To end up in jail. That’s simple.
HEATHER: Yeah, that’s where they belong.
DR. BENNETT: And they will stop that as a company and as a system and as an industry once five or 10 of these corporates find themselves in a one- or two- or three-year vacation.
HEATHER: Hopefully longer than that. (Laughs.) Hopefully longer than that.
LEE: Well, thank you again. We hope you’ll join us on another episode, and as Heather mentioned, we will post all your links and we’ll also have your information on our website.
DR. BENNETT: Again, I appreciate so much support that you all have given me for the last 10, 12 years that I’ve been doing this journey. But I will say that Linda and I and a couple others, one from Britain, a woman in the U.S., and a student, we have collaborated on an update on the Cipro- and Levaquin-associated toxicities which will be published in eClinicalMedicine, which is a Lancet journal, as soon as they go through the last round of reviews, which it seems to me that they’ll take, and then a copy edit, so we’ll have a very informative paper. That paper reviews how the various toxicities from fluoroquinolones have been reviewed and analyzed in six different geographic regions – the U.S., Canada, Australia, Japan, New Zealand, and I forgot one in there. But the thing that’s amazing – that U.S. – oh, Great Britain; it’s separate because it’s no longer part of the EU – the U.S. and the EU and now Great Britain have made strongly definitive statements, these drugs are not first-line therapies. The other three regions – Australia, Japan, and New Zealand – do not make similar concerns. And the more recent side effects that have been known is aortic aneurysms, aortic valve rupture. And again, there’s not complete agreement on this but there’s been a “dear doctor” letter sent out in Europe; in the U.S., no “dear doctor” letter. We want to harmonize these safety messages for the entire world, not just the U.S., and that’s what we want to harmonize. People shouldn’t have to read six different labels and get six different opinions, especially on this, and particularly on this worldwide, terrible and life-threatening and life-ending side effect.
HEATHER: Well, thank you so much. Just really appreciate you, and know that the work you’ve done has just impacted us and our lives and we thank you.
DR. BENNETT: My pleasure.
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>>> ISS astronauts exposed to mutant superbugs that evolved in space
Independent
by Vishwam Sankaran
June 11, 2024
https://news.yahoo.com/news/iss-astronauts-exposed-mutant-superbugs-044145512.html
ISS astronauts exposed to mutant superbugs that evolved in space
Scientists have discovered a superbug notorious for being resistant to drugs in samples isolated from the International Space Station, sparking concerns for astronaut health.
They found 13 strains of the bacterium Enterobacter bugandensis which is known to be multidrug resistant.
The findings suggest these bacterial strains mutated under the stress of the space environment and became genetically distinct from their Earth counterparts.
On Earth, Enterobacter bugandensis is mainly found in clinical specimens, including from the human gut.
It’s usually a harmless bacterium inhabiting the gut but can act as an opportunistic pathogen, co-infecting people with compromised immunity.
The bacterium is also known to transfer its genome or obtain DNA from other organisms.
This means it possesses harmful traits that can lead to a “plethora of infections”, researchers said.
The superbug can persist on the ISS for long periods, co-existing with multiple other microorganisms.
Scientists said that the closed human environment of the ISS offers a unique extreme environment with microgravity, radiation and elevated carbon dioxide levels that force such microbes to adapt in order to thrive.
In a study published in the journal Microbiome, researchers found that the bacterium from the ISS sample developed a method to evade the action of many different types of antibiotics.
This is usually seen in pathogens recognised for their formidable resistance to antimicrobial treatments on Earth.
Over a two-year study period, scientists isolated 13 different strains of multidrug-resistant Enterobacter bugandensis from various locations within the ISS.
“The singular nature of the stresses of the space environment, distinct from any on Earth, could be driving these genomic adaptations,” researchers noted.
Scientists also mapped the prevalence and distribution of the bacterium across the ISS over time.
The findings shed light on the factors that could contribute to the dominance and succession of Enterobacter bugandensis in the space station.
By assessing such microbes, they said better preventive measures can be developed to protect the health of astronauts.
The findings underscore the need for “robust preventive measures” to ensure the health and safety of astronauts by mitigating risks associated with potential pathogenic threats, scientists said.
The findings also have implications for safety measures in terrestrial settings such as hospital ICUs and surgical theatres, they added.
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Re-post - Gadolinium toxicity from MRI scans -
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174585381
>>> One of the biggest radiological concerns in recent years is the safety of GBCAs used in magnetic resonance imaging (MRI). As a study showed that gadolinium deposited in the brain and remained there, radiologists began to question the safety of gadolinium 2 . Results showed that the high signal intensity in patients’ brains is correlated with the number of GBCAs administrated. The new findings have sparked a major debate in radiology about the safety of these agents. For all GBCAs of MRI, the Food and Drug Administration (FDA) mandates a new class warning and additional safety precautions in terms of gadolinium staying in the patients’ bodies, including the brain, for months to years after taking these medications 3 .
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574993
But there is growing evidence that tiny particles of gadolinium remain in the body – including the brain – causing serious side effects in some people, says kidney researcher Brent Wagner, MD, an associate professor in The University of New Mexico Department of Internal Medicine.
“We’ve come to the conclusion if a living organism gets this stuff there’s a chance that these weird particles can form, and my suspicion is this is what triggers this reaction,” says Wagner, who also serves as a staff physician at the Raymond G. Murphy Veterans Affairs Medical Center in Albuquerque. “It’s probably distributing everywhere in the body once someone gets it.”
Reports first started emerging about 15 years ago that some patients who had received the gadolinium contrast agent were experiencing a painful, debilitating skin condition called systemic fibrosis, which causes skin thickening and tightening in the joints and extremities, as well as internal organ damage.
At first, it was assumed that the reaction only occurred in patients with pre-existing kidney disease, but it later became clear that it also occurs in people with healthy kidneys, Wagner says.
“The kidneys themselves are not the problem,” he says. “There is long-term retention of gadolinium – a known toxic metal – regardless of the brand and irrespective of kidney function. There are thousands of members of social media groups focused on the chronic adverse effects of gadolinium-based contrast agents.”
Now, Wagner leads a team of researchers exploring how gadolinium triggers the systemic reaction in some patients.
https://hsc.unm.edu/news/2022/02/doctor-researches-toxic-side-effects-rare-earth-metals-mri.html
Gadolinium offers extra insight into our body’s condition. But, is it safe?
Gadolinium-based contrast agents (GBCAs) were safely delivered to millions of patients throughout the world since 1988, and their usage has definitely benefitted many individuals by allowing doctors to detect neurological disorders earlier and more accurately. GBCAs frequently have minor side effects. Injection-site discomfort, nausea, itching, rash, headaches, and dizziness are the most prevalent adverse effects. Patients with significant renal issues are more likely to experience serious, but uncommon side effects, including gadolinium poisoning and nephrogenic systemic fibrosis 1 .
One of the biggest radiological concerns in recent years is the safety of GBCAs used in magnetic resonance imaging (MRI). As a study showed that gadolinium deposited in the brain and remained there, radiologists began to question the safety of gadolinium 2 . Results showed that the high signal intensity in patients’ brains is correlated with the number of GBCAs administrated. The new findings have sparked a major debate in radiology about the safety of these agents. For all GBCAs of MRI, the Food and Drug Administration (FDA) mandates a new class warning and additional safety precautions in terms of gadolinium staying in the patients’ bodies, including the brain, for months to years after taking these medications 3 .
It is known that patients with renal insufficiency cannot filter the gadolinium from their body, so it is included as a FDA warning label on the contrast packaging. However, there was less evidence showing patient safety issues in those with normal renal function. Boxed warnings are also mentioned for recognized hypersensitivity relationships that can arise in individuals, especially in those with allergic diseases. Using GBCA in MRI has been questioned in recent years as evidence has emerged linking gadolinium to nephrogenic systemic fibrosis (NSF) and gadolinium deposition. Although most gadolinium is removed by urine after an MRI scan, a minimal amount stays and can accumulate over time, according to research published in 2017. This is an important concern for people who need to have MRI scans on a frequent basis 1 . Linear and macrocyclic agents are the two types of GBCAs depending on their chemical forms. Several studies indicated that the linear agents remain more in the brain than macrocyclic agents. However, new research has revealed that all treatments, including macrocyclic, leave some gadolinium in the brain. While gadolinium accumulation in the brain has been the focus of attention in recent years, the authors claimed that, in animal tests, 100 times more gadolinium was found to be retained in the skin and bones than in the brain 4 . The patients with multiple sclerosis (MS) should have brain MRIs both during relapse and remission (every few months) to assess disease activity. In the individuals with MS, the dentate nucleus (DN) T1 hyperintensity was detected 5 .
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>>> Flood of Fake Science Forces Multiple Journal Closures tainted by fraud
THE WALL STREET JOURNAL
By Nidhi Subbaraman
May 14, 2024
https://joannenova.com.au/2024/05/so-much-for-peer-review-wiley-shuts-down-19-science-journals-and-retracts-11000-fraudulent-or-gobblygook-papers/
https://www.wsj.com/science/academic-studies-research-paper-mills-journals-publishing-f5a3d4bc
Fake studies have flooded the publishers of top scientific journals, leading to thousands of retractions and millions of dollars in lost revenue. The biggest hit has come to Wiley, a 217-year-old publisher based in Hoboken, N.J., which Tuesday will announce that it is closing 19 journals, some of which were infected by large-scale research fraud.
In the past two years, Wiley has retracted more than 11,300 papers that appeared compromised, according to a spokesperson, and closed four journals. It isn’t alone: At least two other publishers have retracted hundreds of suspect papers each. Several others have pulled smaller clusters of bad papers.
Although this large-scale fraud represents a small percentage of submissions to journals, it threatens the legitimacy of the nearly $30 billion academic publishing industry and the credibility of science as a whole.
Scientific papers typically include citations that acknowledge work that informed the research, but the suspect papers included lists of irrelevant references. Multiple papers included technical-sounding passages inserted midway through, what Bishop called an “AI gobbledygook sandwich.” Nearly identical contact emails in one cluster of studies were all registered to a university in China where few if any of the authors were based. It appeared that all came from the same source.
One of those tools, the “Problematic Paper Screener,” run by Guillaume Cabanac, a computer-science researcher who studies scholarly publishing at the Université Toulouse III-Paul Sabatier in France, scans the breadth of the published literature, some 130 million papers, looking for a range of red flags including “tortured phrases.”
Cabanac and his colleagues realized that researchers who wanted to avoid plagiarism detectors had swapped out key scientific terms for synonyms from automatic text generators, leading to comically misfit phrases. “Breast cancer” became “bosom peril”; “fluid dynamics” became “gooey stream”; “artificial intelligence” became “counterfeit consciousness.” The tool is publicly available.
Generative AI has just handed them a winning lottery ticket,” Eggleton of IOP Publishing said. “They can do it really cheap, at scale, and the detection methods are not where we need them to be. I can only see that challenge increasing.”
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>>> Merck to buy eye-focused drug developer EyeBio for as much as $3 bln
Reuters
by Christy Santhosh
May 29, 2024
https://www.reuters.com/markets/deals/merck-acquire-eye-drug-company-eyebio-up-3-bln-2024-05-29/
May 29 (Reuters) - Merck (MRK.N), opens new tab on Wednesday agreed to buy privately held biotech EyeBio for as much as $3 billion, as it looks to diversify its portfolio of experimental drugs with treatments for eye diseases.
The drugmaker agreed to pay $1.3 billion in cash and another $1.7 billion in future milestone-based payments for EyeBio, and will gain access to its retinal disease drug Restoret as part of the deal.
The deal is the latest in a string of recent acquisitions by Merck to reduce its reliance on blockbuster immunotherapy Keytruda, which is expected to face rivals by the end of the decade when it is set to lose patent protection
Merck had said in February it was in the market for deals of up to $15 billion. Its recent acquisitions include a $10.8 billion deal for Prometheus Biosciences in 2023 and the purchase of Elanco's (ELAN.N), aqua business for $1.3 billion in February this year.
Merck's proposed acquisition of EyeBio would boost its limited presence in the eye diseases space, BMO Capital Markets analyst Evan Seigerman wrote in a research note.
While the deal was on the smaller side, "we are encouraged by the progress Merck continues to make diversifying its revenue base ahead of its Keytruda (loss of exclusivity)", he said.
Restoret is expected to enter a mid- to late-stage trial as a treatment for diabetic macular edema, a type of swelling in the eye, in the second half of 2024.
It is also being tested in patients with neovascular age-related macular degeneration, a disease which leads to abnormal blood vessel growth in the eye and affects more than 200 million people worldwide.
EyeBio, which operates as Eyebiotech Ltd, has operations in the U.S. and the UK. It was founded by SV Health Investors, which is backed by Kate Bingham — the former head of the UK's COVID-19 vaccine taskforce.
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RespireRx - >>> Ampakines Stimulate Diaphragm Activity after Spinal Cord Injury
https://pubmed.ncbi.nlm.nih.gov/34806433/
Acute ampakines increase voiding function and coordination in a rat model of SCI
https://pubmed.ncbi.nlm.nih.gov/38451184/
Ampakines increase diaphragm activation following mid-cervical contusion injury in rats
https://pubmed.ncbi.nlm.nih.gov/38582278/
Ampakines stimulate phrenic motor output after cervical spinal cord injury
https://pubmed.ncbi.nlm.nih.gov/32949571/
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>>> RespireRx Pharmaceuticals Inc. Announces a Department of Defense Award to Fund a Phase 2 Clinical Study to Determine the Safety and Efficacy of CX1739, its Lead AMPAkine, to Improve Bladder Function in Patients with Spinal Cord Injury
RespireRX Pharmaceuticals Inc.
May 29, 2024
https://finance.yahoo.com/news/respirerx-pharmaceuticals-inc-announces-department-121500944.html
Glen Rock, N.J., May 29, 2024 (GLOBE NEWSWIRE) -- RespireRx Pharmaceuticals Inc. (OTC Pink Markets: RSPI) (RespireRx or the Company), focused on the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is delighted to announce that the Department of Defense (DOD) has approved a $1.8 million translational research award to Shirley Ryan AbilityLab to fund a two stage Phase 2A and 2B clinical study in order to determine the safety and efficacy of CX1739, its lead clinical AMPAkine, to improve bladder function and motor activity in individuals with spinal cord injury (SCI). This grant award supports the ongoing collaboration among scientist teams led by Milap Sandhu, PT, PhD, research scientist at Shirley Ryan AbilityLab, a rehabilitation research hospital in Chicago, and Dr. Arnold Lippa from RespireRx and Dr. David Fuller from the University of Florida.
The U.S. Army Medical Research Acquisition Activity, in support of the Congressionally Directed Medical Research Program (CDMRP), is the awarding and administering acquisition office and this work will be supported by the Department of Defense, in the amount of $1,793,411, through the Spinal Cord Injury Research Program under Award No. HT94252410497. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs or the Department of Defense.
Shirley Ryan AbilityLab has been ranked number one in rehabilitation by U.S. News & World Report since 1991 and cares for patients with the most severe, complex conditions, including SCI.
As the Principal Investigator, Dr. Sandhu will conduct the clinical trials at Shirley Ryan AbilityLab. Dr. Sandhu and Shirley Ryan AbilityLab have been allocated $1.8 million to conduct the actual clinical study of which RespireRx has been allocated $252,200 to manufacture and formulate the clinical material, as well as update and submit the CX1739 investigational new drug application (IND). Budget projections have determined that these amounts should be sufficient to pay for manufacturing and clinical costs and the plan is to begin testing in patients by the 4th quarter 2024. The trial will consist of two stages, the first being a Phase 2A will be an ascending single dose safety and efficacy study and the second Phase 2B will consist of a double blind, placebo-controlled study in which participants will be given CX1739 or placebo twice daily for a total of seven days.
As we have disclosed in an earlier press release and peer review publications, traumatic SCI often results in neurogenic bladder dysfunction that produces a plethora of urological complications leading to reductions in the quality of life and an increased risk of premature death. Restoration of bladder function is ranked as one of the highest priorities by individuals with SCI (Bourbeau et al., Spinal Cord 58:1216–1226; 2020). Current treatment approaches usually require interventions such as catheterization for urinary voiding, which have their own set of potentially significant risks and complications. World-wide incidence rates range from 12 to 59 cases per million depending on the country (Amidei et al., Spinal Cord 60:812-819; 2022) and of these 70 - 84% showed neurogenic bladder dysfunction (Kumar et al., World Neurosurgery 113:e345–e363;2018).
“I am delighted and grateful for this government funding that now allows us to extend Dr. Fuller's preclinical studies into the human domain. If CX1739 produces the same effects in humans that it has produced in animals, it potentially represents a novel and needed treatment for SCI,” said Dr. Sandhu.
Dr. Arnold Lippa, CEO and CSO of RespireRx, commented that, “CX1739 has successfully completed multiple Phase 1 safety trials and Phase 2 proof of concept trials demonstrating target engagement. With this new non-dilutive funding, we have begun planning to conduct translational, Phase 2 studies in SCI patients late this year. We believe that this research has the potential to represent a breakthrough in the treatment of SCI, where it is badly needed.”
He added that, “It has been a pleasure to work with Dr. Fuller, a long-time RespireRx collaborator, and his team of scientists. In a series of important studies funded by grants from the National Institutes of Health and published in a number of peer reviewed articles, he has demonstrated the ability of RespireRx’s lead AMPAkines to improve motor nerve activity and muscle function in a number of animal models of SCI, including respiration and bladder functions.
About RespireRx Group
RespireRx Pharmaceuticals Inc. and its subsidiaries and business units (RespireRx Group) are discovering and developing medicines for the treatment of psychiatric and neurological disorders, with a focus on treatments that address conditions affecting millions of people, but for which there are few or poor treatment options, including epilepsy, pain, attention deficit hyperactivity disorder (ADHD), recovery from SCI, certain neurological orphan diseases and obstructive sleep apnea (OSA). The RespireRx Group is developing a pipeline of new and repurposed drug products based on our broad patent portfolios for two drug platforms: (i) neuromodulators, which include GABAkines and AMPAkines, proprietary chemical entities that positively modulate (positive allosteric modulators or “PAMs”) GABAA receptors and AMPA-type glutamate receptors, respectively, and (ii) pharmaceutical cannabinoids, which include dronabinol, a synthetic compound that acts upon the nervous system’s endogenous cannabinoid receptors.
The RespireRx Group holds exclusive licenses and owns patents and patent applications or rights thereto for certain families of chemical compounds that claim the chemical structures and their uses in the treatment of a variety of disorders, as well as claims for novel uses of known drugs.
EndeavourRx: Neuromodulators
AMPAkines. Through an extensive translational research effort from the cellular level through Phase 2 clinical trials, RespireRx has developed a family of novel, low impact AMPAkines, including CX717, CX1739 and CX1942 that may have clinical application in the treatment of CNS-driven neurobehavioral and cognitive disorders, SCI, neurological diseases, and certain orphan indications. Our lead clinical compounds, CX717 and CX1739, have successfully completed multiple Phase 1 safety trials. Both compounds have also completed Phase 2 proof of concept trials demonstrating target engagement, by antagonizing the ability of opioids to induce respiratory depression.
AMPAkines have demonstrated positive activity in animal models of ADHD, results that have been extended translationally into statistically significant improvement of symptoms observed in a Phase 2 human clinical trial of CX717 in adult patients with ADHD. Statistically significant therapeutic effects were observed within one week. We believe AMPAkines may represent a novel, non-stimulant treatment for ADHD with a more rapid onset of action than alternative non-stimulants, such as Straterra® (atomoxetine), and without the drawbacks of amphetamine-type stimulants. In a series of important studies funded by grants from the National Institutes of Health and published in a number of peer reviewed articles, Dr. David Fuller (University of Florida), a long-time RespireRx collaborator, has demonstrated the ability of CX1739 and CX717, RespireRx’s lead AMPAkines, to improve motor nerve activity and muscle function in a number of animal models of SCI. The DOD has recently approved a $1.8 million grant to fund a Phase 2A/2B clinical study of CX1739 in individuals with SCI.
GABAkines. Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. and on behalf of its EndeavourRx business unit, RespireRx has in-licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific, subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. EndeavourRx currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.
KRM-II-81 has displayed a high degree of anti-convulsant activity in a broad range of preclinical studies, including in treatment resistant and pharmaco-resistant animal models. Not only was KRM-II-81 highly effective in these models, but pharmaco-resistance or tolerance did not develop to its anti-convulsant properties. These latter results are particularly important because pharmaco-resistance occurs when medications that once controlled seizures lose efficacy as a result of chronic use and it is a principal reason some epileptic patients require brain surgery to control their seizures. In support of its potential clinical efficacy, translational studies have demonstrated the ability of KRM- II-81 to dramatically reduce epileptiform electrical activity when administered in situ to brain slices excised from treatment-resistant epileptic patients who underwent surgery.
In addition, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In intact animal models of pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.
ResolutionRx: Pharmaceutical Cannabinoids.
ResolutionRx Ltd (Australian Company Number a/k/a ACN 664 925 651) was formed in Australia on January 11, 2023 by RespireRx as an unlisted public company. RespireRx has contributed by sublicense and license with ResolutionRx, its sleep apnea drug development program subject to certain liabilities. ResolutionRx now engages in the research and development (R&D) associated with that program, initially for the development of a new formulation of dronabinol for use in a Phase 3 clinical trial and the filing of regulatory approval for the treatment of OSA. The current total budget for that program over the next several years is approximately US$16.5 million, most, but not all of which is expected to be eligible for the Australian R&D Tax Incentive (R&DTI). The R&DTI in the case of ResolutionRx is anticipated to be approximately 43.5% of qualified R&D expenditures. Dronabinol, an endocannabinoid receptor agonist, has already demonstrated significant improvement in the symptoms of OSA in two Phase 2 clinical trials. OSA is a serious respiratory disorder that impacts an estimated 90 million people in the United States, Australia, the United Kingdom and Germany and that has been linked to increased risk for hypertension, heart failure, depression, and diabetes. There are no approved drug treatments for OSA.
Because dronabinol is already FDA approved for the treatment of AIDS related anorexia and chemotherapy induced nausea and vomiting, RespireRx and ResolutionRx further believe that its repurposing strategy would only require, in the United States, approval by the FDA of a 505(b)(2) new drug application (NDA), an efficient regulatory pathway that allows the use of publicly available data.
Additional information about RespireRx and the matters discussed herein can be obtained on the RespireRx website at www.RespireRx.com or RespireRx’s filings with the U.S. Securities and Exchange Commission (the SEC) at www.sec.gov. Additional information about ResolutionRx and the matters discussed herein can be obtained on the ResolutionRx website at https://www.resolutionrx.com.au.
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Bigworld, With Acurx, hopefully partnering interest is as keen as it sounds.
One thing with the reliance on ATM funding is that Luci will likely sell some shares whenever the stock price gets a pop. Investors know this, so this could mute the periodic bounces. Luci seems very averse to dilution, and is raising small sums incrementally via the ATM. This approach has its advantages, but it could also adversely affect the partnering and M+A terms by keeping the stock price muted.
On the clinical side, one problem was the lack of availability of key durability data announced back in Jan. It turned out that only 5 of the 15 Ibeza patients from the Phase 2b had agreed to be followed longer term (!) This is a big problem since the durability data is so key in showing Ibeza's main advantage over Vancomycin (lack of relapses). The 5 patients who agreed to the follow up analysis didn't relapse, which is good, but what about the other 10 Ibeza patients? Presumably there's no way to get this missing data, but I'm figuring these patients could at least be contacted on the phone by Acurx and/or interested pharma partners, and asked about their symptoms, whether the GI distress had returned, etc. So not exactly hard data, but still very useful anecdotal evidence of durability.
The clinical side is also clouded by the fact that one of the Ibeza Phase 2b patients failed on efficacy (1 out of the 16 Ibeza patients). Meanwhile, none of the Vancomycin patients failed on efficacy (0 out of 16). So this is a red flag, and when announced in early Nov the stock was cut in half.
Another problem on the clinical side is that in the follow up durability data in Jan, all the Vanc patients who had agreed to be followed longer term showed no relapses (7 out of 7), which was the same as Ibeza (5 out of 5). Durability is the key theoretical advantage for Ibeza, but unfortunately this could not be demonstrated by such a tiny Phase 2b, made even tinier because so many patients had refused to be followed longer term.
So lots of unknowns, but Luci's recent comments sound hopeful that there will be significant partnering interest.
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gfp: You could be right on the timing of the full release. It certainly gives me reason for optimism.
Full transcript - >>> Q1 2024 Acurx Pharmaceuticals Inc Earnings Call
Thomson Reuters
May 15, 2024
https://finance.yahoo.com/news/q1-2024-acurx-pharmaceuticals-inc-024052823.html
Participants
David P. Luci; Co-Founder, President, CEO, Corporate Secretary & Director; Acurx Pharmaceuticals, Inc.
Robert G. Shawah; Co-Founder & CFO; Acurx Pharmaceuticals, Inc.
Robert J. DeLuccia; Co-Founder & Executive Chairman; Acurx Pharmaceuticals, Inc.
Antonio Eduardo Arce; MD of Equity Research & Senior Healthcare Analyst; H.C. Wainwright & Co, LLC, Research Division
James Francis Molloy; MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst; Alliance Global Partners, Research Division
Unidentified Participant
Presentation
Operator
Hello, and welcome to the Acurx Pharmaceuticals First Quarter 2024 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference is being recorded. It's now my pleasure to turn the conference over to CFO, Robert Shawah. Please go ahead.
Robert G. Shawah
Thank you, Kevin. Good morning, and welcome to our call. This morning we issued a press release providing financial results and company highlights for the first quarter of 2024, 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; as well as our Executive Chairman, Bob DeLuccia. After that, I'll provide some highlights of the financials from the quarter ended March 31, 2024, then turn the call back over to Dave and Bob for their closing remarks.
As a reminder, during today's call, we'll be making certain forward-looking statements. 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 the 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 on Tuesday, May 14, 2024.
You're cautioned not to place undue reliance on these forward-looking statements, and Acurx disclaims any obligation to update such statements anytime in the future. This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast today, May 15, 2024.
I'll now turn the call over to Dave Luci. Dave?
David P. Luci
Thanks, Rob. Good morning, everyone, and thanks for joining us to review our financial results for the first quarter and also to hear some exciting recent updates. Then we'd be pleased to take any questions. First, I'll summarize some of our key activities for the first quarter of 2024, or in some cases, shortly thereafter. In January, we announced positive comparative microbiology and microbiome data for ibezapolstat, our lead antibiotic candidate in C. diff patients from the Phase IIb clinical trial segment.
Ibezapolstat outperformed vancomycin, a standard of care, showing eradication of fecal C. difficile at day 3 of treatment in 15 of 16 treated patients, 94%, versus vancomycin, which had eradication of C. difficile in 10 of 14 treated patients or 71%. Additional data from the Phase IIb clinical trial showed ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacteria species believed to confer health benefits, including preventing recurrent C. diff infection.
Additional data from exploratory endpoints will provide further favorable separation between these 2 therapeutic options in our Phase III clinical trial program and ultimately in the marketplace, if approved. We remain particularly excited about the dual impact of ibezapolstat to treat acute C. difficile on the one hand, while appropriately managing the long-term care of each patient's microbiome, which we believe is truly exceptional for antibiotic therapy.
Having robust preclinical, clinical and manufacturing data to date, we submitted, in January, a formidable information package to the FDA, along with a request for an end of Phase II meeting, which was granted on February 26, and the meeting was convened on April 17. At the FDA meeting, we reached agreement on key elements of our Phase III program. including, importantly, agreement with the FDA regarding readiness to proceed to Phase III, as well as agreement on the regulatory pathway for a new drug application filing for marketing approval in the U.S. We will press release further details on the FDA meeting premarket this morning.
In February, we announced that the European Medicines Agency approved our application to be designated as a small to medium-sized enterprise or SME in Europe, which provides for certain benefits, including fee reductions and other support from the agency for seeking a marketing authorization in Europe. We attended the European Society of Microbiology and Infectious Disease or ESCMID Scientific Congress in April 2024, where Dr. Kevin Garey, Professor and Chair, University of Houston, College of Pharmacy, and the Principal Investigator for Microbiology and Microbiome aspects of our clinical trial program, and our Scientific Advisory Board member, provided an oral presentation of Phase II data entitled, "A Phase II Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of C. difficile Infection". The presentation included additional analyses of clinical and microbiological data and is available on our website at www.acurxpharma.com. The complete Phase II results are being prepared for submission to a prominent scientific journal for publication this year.
Throughout the rest of this year, we'll continue to roll out our Phase II results in either oral presentations or scientific posters, or in some cases both, which will include results from new analyses as data become available at various prominent scientific conferences, including the Houston C. diff & Microbiome Conference later this month, the Anaerobe Society of the Americas Annual Conference in July, the World Antimicrobial Resistance Conference in September. Also in September is the International C. diff Symposium, and of course, the Annual Meeting of the Infectious Disease Society of America, or ID Week, in October.
Throughout the first quarter, we continued preparations for Phase III trials, including advances in micro and manufacturing, CRO selection and clinical site screening, and building a team of international drug development experts to support our Phase III mandate. To ensure Phase III clinical trial enrollment as quickly as possible, we're adding substantially more clinical trial sites, way above the number used to conduct the U.S.-only Phase II trials.
We're now finalizing costs and time lines and our plan is to conduct the required 2 Phase III registration trials consecutively, not concurrently, given the size of our company, and need to use our financial resources most efficiently. The time line to conduct our Phase III trials is not a concern since ibezapolstat will have a rolling 10 years of regulatory exclusivity in the U.S. from the date of the FDA approval, with similar exclusivity available in Europe, the U.K., Japan, and Canada.
We will continue to seek a strategic transaction for the company, including a potential partnership for the further development and potential commercialization of ibezapolstat, alongside preparation for Phase III and our build-out strategy. At this time, we have no commitments to our potential partners or others to report. But now having FDA confirmation of the registration plan, this has become an active initiative.
As we've consistently reported, ibezapolstat clinical results continue to outperform in a series of potentially life-threatening infection. The CDC categorizes C. difficile as an urgent threat and calls for new classes of antibiotics for initial treatment that also have a low incidence of recurrence. Ibezapolstat is also FDA fast track designated for the treatment of C. difficile infection.
Initially, we believe ibezapolstat, if approved, could make a favorable impact by reducing the cost burden of recurrent C. diff infection on the U.S. health care system, which is estimated at $4.7 billion annually. We do believe the best is yet to come.
And now back to our CFO, Rob Shawah, to guide you through the highlights of our financial results for the first quarter. Rob?
Robert G. Shawah
Thanks, Dave. Our financial results for the first quarter ended March 31, 2024, were included in our press release issued earlier this morning. The company ended the quarter with cash totaling $8.9 million compared to $7.5 million as of December 31, 2023. During the first quarter, the company sold an additional 1,121,793 shares under its ATM financing program with gross proceeds of approximately $4.4 million.
Research and development expenses for the 3 months ended March 31, 2024, were $1.6 million compared to $1 million for the 3 months ended March 31, 2023. The increase was due primarily to an increase in manufacturing-related costs during the quarter. General and administrative expenses for the 3 months ended March 31, 2024, were $2.8 million compared to $1.9 million for the 3 months ended March 31, 2023. The increase was due primarily to a $0.7 million increase in professional fees and a $0.2 million increase in noncash share-based compensation.
The company reported a net loss of $4.4 million or $0.28 per diluted share for the 3 months ended March 31, 2024, compared to a net loss of $2.9 million or $0.25 per diluted share for the 3 months ended March 31, 2023, all for the reasons we previously mentioned. The company had 15,757,102 shares outstanding as of March 31, 2024.
With that, I'll turn the call back over to Dave. Dave?
David P. Luci
Thanks, Rob, and thanks to all of you for joining us today. I'll now ask Bob DeLuccia, our Executive Chairman, who managed the FDA post-Phase II meeting process, to provide his perspective on the FDA meeting in the company's Phase III mandate. Bob?
Robert J. DeLuccia
Yes. Thanks, Dave. So let me just add a few thoughts on top of Dave's comments about our end of Phase II meeting with the FDA. In general, it was a very thorough, productive, and successful meeting regarding 4 things.
First, we had overall agreement that was reached based upon the strength of our preclinical and Phase II clinical trial results, including the anticipated safety database, we're ready to move forward with plans for our Phase III program.
Second, with respect to the Phase III clinical trial design, as expected, it will be the same design as our Phase IIb trial, which is noninferiority to vancomycin, with the primary endpoint being clinical cure after 10 days of treatment, and a secondary endpoint of sustained clinical cure about 30 days after the end of treatment.
Third, we agreed on the statistical analysis patient population, which will be a modified intent to treat or what's called MITT population, with an estimated 450 subjects in that MITT group. And this is roughly what we had expected and will now be in sync with requirements for an EMA clinical trial authorization.
And lastly, agreement on the registration program for 2 noninferiority trials versus vancomycin, which would be required for marketing approval. Now I'd also add that we were very pleased with suggestions from the FDA, including ultimate labeling and overall supportive tone of the FDA from our submitted data to date and our plan going forward. So bottom line, we now have a complete regulatory road map to move forward with our Phase III program, which is the last clinical development step toward marketing registration of ibezapolstat globally. For a small entrepreneurial company like Acurx, this is a very significant milestone that we've reached.
And Dave, if you don't mind, I'd like to add one more thing just on top of what you said. Recall that ibezapolstat has FDA fast track designated status due to the urgent need classification by the U.S. CDC for new classes of antibiotics. And there are similar classifications like this available in other geographies, including Europe, the U.K., Japan and Canada. If approved, ibezapolstat will be the first new class of antibiotics brought to the market in over 3 decades. So we've got no time to waste to get this new product over the goal line. And with the continued support of all our shareholders, we have a clear vision and a strong passion to be successful for the ultimate benefit of patients who need better treatment for C. difficile infection and all our stakeholders and, in general, for better public health. Kevin?
Question and Answer Session
Operator
(Operator Instructions) Our first question today is coming from Ed Arce from H.C. Wainwright.
Antonio Eduardo Arce
Bob, I appreciate the comments at the end. Those were some of the questions I had regarding the specifics around the trial. A couple of follow-ups there. Firstly, the 450 patients or subjects that you mentioned, is that the total number for the trial? And also, the usual requirement from the FDA of 2 well-designed pivotal studies. I want to just confirm that the Phase Ib is being considered as one of those 2. And so this upcoming trial would be the final study?
Secondly, I wanted to ask about the costs and time lines. I know that you said that those are currently being finalized. But any preliminary or early commentary around those would be helpful for us. And then lastly, around the strategic partners and your efforts now that you characterized as being active, now that you have a pathway for a pivotal study. I'm wondering, although you don't have any current commitments, do you have any active discussions at this point? Thanks so much.
David P. Luci
Thank you for your questions, Ed. The last question being the easiest, I'll hit that 1 first. So we have several active discussions at the moment. Nothing to report. But for example, the company will be well represented at the BIO CEO conference in San Diego, and my schedule is chock full. So there's a lot of activity. We felt it most appropriate, before making outbound calls, to have the FDA piece to the puzzle in place, because we now are truly Phase III ready and that removes another piece of the puzzle in terms of things being set in stone. So that's all set.
On the first question, with regard to the 450 MITT patients, that's the total MITT patients for each of 2 Phase III registration trials. So the Phase IIb is not considered a registration trial. You may recall the small numbers of patients. And quite frankly, we needed a lot more patients to have satisfactory safety database for an NDA application thereafter. So it's 450 patients MITT for each of 2 trials, for a total of 900.
And to your question, we are still going through the cost things. So we don't know exactly how much it will cost. And in some cases, if we have a partnership, it may be that some of the work that we would have paid for would be internalized by a fully integrated pharma company that will be side-by-side with us with mutual interest to get the Phase III program done as quickly as possible, and using our Phase III data for filing in Europe, the U.K., Japan. So the MITT piece to the puzzle was a quick conversation with the FDA, because really, you need that to get to file for approval in Europe and the U.K. So by agreeing on that particular point, we were able to avoid further clinical trials beyond the 2 Phase IIIs. And quite literally, we have an equal pathway in the U.S., the U.K. and Europe. So we're kind of delighted with that piece to the puzzle. But I think that's -- is there another piece to your question that I may have missed?
Robert J. DeLuccia
Yes, Dave. Question on time line. I mean I can answer if you'd like to?
David P. Luci
Okay. Time line. Yes, we feel, based on what we spent out so far that would be 1.5 years to 2 years from first patient enrolled.
Robert J. DeLuccia
And Ed, this is Bob. Just to reiterate, too, the 2 Phase III trials are straightforward from the FDA guidelines, October 22, I think it was, guidelines. And that's a very clear path for what's needed for approval and an NDA.
Operator
(Operator Instructions) Your next question is coming from Mike Boyd, a private investor.
Unidentified Participant
Thank you for the update. It's very exciting, and I can't wait to see the next steps. I had a quick question, easy one I hope. Has the company considered a priority review voucher for this application?
David P. Luci
Thanks for the question, Mike. Bob, do you want to hit that one?
Robert J. DeLuccia
Yes. I mean we already have priority review because of our FDA fast track status. So we already have that.
Unidentified Participant
Yes. But the voucher itself is actually -- there's value to that. You could actually sell that if you chose. Current market value is about $100 million. So looking at that as a source of possible funding at some point.
Robert J. DeLuccia
We could certainly take a look.
Unidentified Participant
Okay. Cool. I mean the timing is right to begin thinking about it. It's associated with the NDA. So it's time to put it on the radar if it's something that the FDA would consider.
David P. Luci
Okay.
Operator
Your next question today is coming from James Molloy from Alliance Global Partners.
James Francis Molloy
Guys, I apologize if I missed it on the call. Did you guys state when you anticipate starting the first of the 2 Phase IIIs? And can you walk us through what the all-in cost on the Phase IIIs are anticipated?
David P. Luci
Thanks, Jim, and good morning. We hope to start -- we will be ready to start in the fourth quarter of this year with enrollment with our manufacturing update that we recently received. So we hope to be funded satisfactorily by then in order to start. So that's the gating factor. But yes, we hope to start in the fourth quarter, and then enrollment should take 18 to 24 months. And it's difficult for us to guesstimate exactly how much this is going to cost, because we have a lot of partnering discussions currently ongoing and they're all different. And they all have various internal capabilities that dramatically impact what the Phase III mandate will cost. It's certainly something in the $50 million to $60 million range if we were to do it all independently ourselves. So a partnership would be an appropriate course.
James Francis Molloy
How would you characterize the current partnership environment? And obviously, after Phase III, it's your best deal, you're obviously not there. But how do you characterize sort of going into Phase III, the partnership opportunities you're seeing?
David P. Luci
I would characterize it as pretty robust. I mean, probably my last 20 e-mails in my inbox are people wanting to meet me, and I haven't even looked at the e-mails yet. That's just from overnight. I mean, it's just a lot of interest, and we may not be enrolling in Phase III, but we're Phase III ready. And we know we have a drug from our Phase IIb data. So we have to be patient and we have to take the right deal.
And when things come along that are going to constitute 60% of the company being lost to a round of investment, then sometimes it's the deals that you don't do that make the most sense. So we're trying to be judicious about raising capital as nondilutively as possible, knowing that we have a drug, and we're Phase III ready. And there aren't a lot of Phase III antibiotics out there right now, especially not in a $1 billion-plus market, where you have a reasonable chance to be frontline therapy.
James Francis Molloy
Maybe last questions on my end. On the design, I know that, obviously, 1 year, 1.5 years to get to run the first of the Phase IIIs. Is there an opportunity for any interim looks and any thoughts on timing on that? And then any update on the PASTEUR Act? What's going on?
David P. Luci
Yes, I'll leave that -- the question on the PASTEUR Act, I'll leave to Bob. There's some new legislation -- actually old legislation that may be expanded to include antibiotics that treat life-threatening infections that Katie Britt in the Senate has gotten in touch with the Health and Human Services about, but I'll let Bob talk about that.
But the interim look thing, that's kind of like a head fake. I know it's NBA playoff time. So for you NBA fans, the interim look, that would go through an independent committee of scientists and doctors. And if you take an interim look, you necessarily statistically have to add patients to the trial. And the interim look doesn't give you any sense of, percentage-wise, how you're doing with the primary endpoint or secondary endpoints. All it does is this group of experts tell you to either keep going or to stop due to futility. So for the amount of information you get out of that, to me, is not worth adding millions of dollars in time to a trial.
Robert J. DeLuccia
Yes. I agree with you, Dave, on that, for sure. And I hope that answers the question. But remember, this is a blinded trial. So you really can't break the blind. You've got to continue to proceed. I think there was a second question here regarding...
David P. Luci
It was about PASTEUR Act.
Robert J. DeLuccia
What was the question?
David P. Luci
What's going on with the PASTEUR Act?
Robert J. DeLuccia
Yes, PASTEUR Act. There's a lot of effort to try to get that through. Really unlikely going to occur this year under the current political environment. However, there is some activity with a special program that requires a drug to be determined as a material threat in order to get some additional funding from a government organization called BARDA for new classes of antibiotics that are in late-stage clinical trials, namely Phase III.
So this is being circulated as pending legislation, trying to move it forward this year. I wouldn't put a high probability that it's going to get through this year. But if it does, we'll be able to tap into that for some partial funding for our Phase III program.
David P. Luci
Actually, just a slight nuance on that is that the legislation is actually old. It's been approved a long time ago. So what needs to happen is that the scope of the program would need to be expanded, which I understand can be done by HHS on their own. It would need to be expanded to include antimicrobials that treat life-threatening infections. So it doesn't rise to the level of needing a new law, the law is there, it's just the program needs to be expanded to include this new class of things that ultimately would be stockpiled by the Federal government through the Department of Defense.
Operator
We've reached the end of our question-and-answer session. I'd like to turn the floor back over for any further or closing comments.
David P. Luci
We'd just like to thank everyone for participating today, and thank you for your patience and the best is yet to come.
Operator
Thank you. That does conclude today's teleconference. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.
<<<
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Bigworld, Yes, a nice 25% pop today. Here's the full transcript from last week's earning's call (next post). I'm not sure what exactly caused the big spike today, there was no SEC filing, etc, but it might have been that the full transcript of last week's earnings call finally became available (?) Last night I could only find the transcript summary from GuruFocus, and the links to the full transcript didn't link to anything, but now they do. So it could be that the Reuters full transcript was delayed and didn't become available until today in the afternoon, and that would explain the timing of the sudden surge. Just a guess though. Within that full transcript, when asked about the current partnership environment, Luci dropped this quasi bombshell -
>>> I would characterize it as pretty robust. I mean, probably my last 20 e-mails in my inbox are people wanting to meet me, and I haven't even looked at the e-mails yet. That's just from overnight. I mean, it's just a lot of interest, and we may not be enrolling in Phase III, but we're Phase III ready. And we know we have a drug from our Phase IIb data. So we have to be patient and we have to take the right deal. <<<
Those comments weren't included in the GuruFocus partial transcript, which only said that partnering prospects were looking 'robust'. Anyway, around noon today there was some increased buying, then around 1:00 the it really took off, and up she went.
Oh well. I had been considering a modest position, but by today's open, the previous aftermarket gain (3%) was gone, and the stock was down modestly on tiny volume (under 1000 shares). I was surprised, thinking it 'should' be rising, so I shelved the idea of going long, at least for now. Also, the broader market is risky right now due to tomorrow's Nvidia earnings, and if ACXP is already looking weak, why stick your neck out? Anyway, the market once more shows how unpredictable it can be lol..
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gfp: Since we last messaged about the stock it took off. Up 17% since 11 AM. I wonder if some partnership news/rumors are getting out there. That's a pretty big move on a day with ultra low trading volumes on the major indexes.
>>> Acurx Pharmaceuticals, Inc. Reports First Quarter 2024 Results and Provides Business Update
https://ir.acurxpharma.com/press-releases/detail/79/acurx-pharmaceuticals-inc-reports-first-quarter-2024
May 15, 2024
STATEN ISLAND, N.Y., May 15, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "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 first quarter ended March 31, 2024.
Highlights of the first quarter ended March 31, 2024, or in some cases shortly thereafter, include:
On January 17, 2024, we announced positive comparative microbiology and microbiome data for ibezapolstat in CDI patients from the Phase 2b clinical trial segment. Ibezapolstat outperformed vancomycin showing eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 treated patients (94%), versus vancomycin which had eradication of C. difficile in 10 of 14 treated patients (71%).
Additional data from this Phase 2b clinical trial showed ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent recurrence of CDI.
Additional data from exploratory endpoints will provide further favorable separation between these two therapeutic options in our Phase 3 clinical trial program and ultimately in the marketplace, if approved.
An End of Phase 2 Meeting was recently conducted with FDA in April 2024. At the FDA meeting, we reached agreement on key elements of our Phase 3 program and readiness to proceed to Phase 3. We also reached agreement on the regulatory pathway for a new drug application (or NDA) filing for marketing approval in the U.S.
We announced that the European Medicines Agency (or EMA) approved our application to be designated as a small to medium sized enterprise (or SME) in Europe which provides for certain benefits including fee reductions and other support from the EMA for seeking a Marketing Authorization for Europe.
We attended the European Society of Microbiology and Infectious Disease (or ESCMID) scientific congress held in April 2024 where Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy, and the Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member gave an oral presentation of our Phase 2 data entitled: "A Phase 2, Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides difficile Infection." The presentation included additional analyses of clinical and microbiological data and is available on our website at www.acurxpharma.com.
Throughout the rest of this year, we will continue to roll out our Phase 2 results in either oral presentations or scientific posters (in some cases both), which by the way, will include results from new analyses as data become available, at various prominent scientific conferences including:
The Houston Cdiff and Microbiome conference;
The Anaerobe Society of America annual conference;
The World Antimicrobial Resistance conference;
The International Cdifficile Symposium; and
The annual meeting of the Infectious Diseases Society of America (or IDWeek).
First Quarter of 2024 Financial Results
Cash Position:
The Company ended the quarter with cash totaling $8.9 million, compared to $7.5 million as of December 31, 2023. In the first quarter, the Company sold 1,121,793 shares under its ATM financing program, with gross proceeds of approximately $4.4 million.
R&D Expenses:
Research and development expenses for the three months ended March 31, 2024 were $1.6 million compared to $1.0 million for the three months ended March 31, 2023. The increase was due primarily to an increase in manufacturing related costs.
G&A Expenses:
General and administrative expenses for the three months ended March 31, 2024 were $2.8 million compared to $1.9 million for the three months ended March 31, 2023. The increase was due primarily to a $0.7 million increase in professional fees and a $0.2 million increase in non-cash share-based compensation.
Net Income/Loss:
The Company reported a net loss of $4.4 million or $0.28 per diluted share for the three months ended March 31, 2024 compared to a net loss of $2.9 million or $0.25 per diluted share for the three months ended March 31, 2023 for the reasons previously mentioned.
The Company had 15,757,102 shares outstanding as of March 31, 2024.
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:
Wednesday, May 15, 2024
Time:
8:00 a.m. ET
Toll free (U.S. and International):
877-790-1503
Conference ID:
13746308
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate advancing to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). 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 Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial 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).
To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com.
Forward-Looking Statements
Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether ibezapolstat will benefit from the QIDP designation; whether ibezapolstat will advance through the clinical trial process on a timely basis; whether the results of the clinical trials of ibezapolstat will warrant the submission of applications for marketing approval, and if so, whether ibezapolstat will receive approval from the FDA or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other risks and uncertainties described in the Company's annual report filed with the Securities and Exchange Commission on Form 10-K for the year ended December 31, 2023, and in the Company's subsequent filings with the Securities and Exchange Commission. Such forward-looking statements speak only as of the date of this press release, and Acurx disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances after the date of such statements, except as may be required by law.
Investor Contact:
Acurx Pharmaceuticals, Inc.
David P. Luci, President & Chief Executive Officer
Tel: 917-533-1469
Email: davidluci@acurxpharma.com
ACURX PHARMACEUTICALS, INC.
CONDENSED INTERIM BALANCE SHEETS
March 31,
December 31,
2024
2023
(unaudited)
(Note 2)
ASSETS
CURRENT ASSETS
Cash
$8,920,926
$7,474,188
Other Receivable
—
129,159
Prepaid Expenses
187,908
105,776
TOTAL ASSETS
$9,108,834
$7,709,123
LIABILITIES AND SHAREHOLDERS' EQUITY
CURRENT LIABILITIES
Accounts Payable and Accrued Expenses
$3,110,242
$3,042,438
TOTAL CURRENT LIABILITIES
3,110,242
3,042,438
TOTAL LIABILITIES
3,110,242
3,042,438
COMMITMENTS AND CONTINGENCIES
SHAREHOLDERS' EQUITY
Common Stock; $.001 par value, 200,000,000 shares authorized, 15,757,102 and 14,468,229 shares issued and outstanding at March 31, 2024 and December 31, 2023, respectively
15,757
14,468
Additional Paid-In Capital
63,579,577
57,871,070
Accumulated Deficit
(57,596,742)
(53,218,853)
TOTAL SHAREHOLDERS' EQUITY
5,998,592
4,666,685
TOTAL LIABILITIES AND SHAREHOLDERS' EQUITY
$9,108,834
$7,709,123
ACURX PHARMACEUTICALS, INC.
CONDENSED INTERIM STATEMENTS OF OPERATIONS
Three Months Ended
March 31,
2024
2023
(unaudited)
(unaudited)
OPERATING EXPENSES
Research and Development
$1,555,011
$1,015,583
General and Administrative
2,822,878
1,887,374
TOTAL OPERATING EXPENSES
4,377,889
2,902,957
NET LOSS
$(4,377,889)
$(2,902,957)
LOSS PER SHARE
Basic and diluted net loss per common share
$(0.28)
$(0.25)
Weighted average common shares outstanding, basic and diluted
15,472,507
11,639,395
<<<
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>>> Acurx Pharmaceuticals Inc (ACXP) Q1 2024 Earnings Call Transcript Highlights: Key Financial and ...
GuruFocus Research
May 16, 2024
https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-acxp-q1-070055271.html
Cash Position: $8.9 million as of March 31, 2024, up from $7.5 million as of December 31, 2023.
Net Loss: $4.4 million or $0.28 per diluted share for Q1 2024, compared to a net loss of $2.9 million or $0.25 per diluted share for Q1 2023.
Research and Development Expenses: $1.6 million for Q1 2024, up from $1 million for Q1 2023.
General and Administrative Expenses: $2.8 million for Q1 2024, up from $1.9 million for Q1 2023.
Shares Outstanding: 15,757,102 as of March 31, 2024.
ATM Financing: Sold an additional 1,121,793 shares with gross proceeds of approximately $4.4 million during Q1 2024.
Release Date: May 15, 2024
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
Positive Points
Ibezapolstat showed superior efficacy in eradicating C. difficile compared to vancomycin in Phase IIb trials, with a 94% success rate versus 71% for vancomycin.
Ibezapolstat has demonstrated the ability to preserve and allow regrowth of key gut bacteria, potentially reducing the recurrence of C. diff infections.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) has successfully reached agreement with the FDA on key elements of the Phase III program, indicating readiness to proceed to the next phase of clinical trials.
The company has secured SME status in Europe, providing benefits such as fee reductions and support from the European Medicines Agency.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) has a robust financial position with an increase in cash from $7.5 million to $8.9 million and successful additional share sales generating $4.4 million.
Negative Points
The company reported an increased net loss of $4.4 million for Q1 2024, up from $2.9 million in the same period the previous year.
Research and development expenses increased significantly, from $1 million to $1.6 million, due to higher manufacturing-related costs.
General and administrative expenses also rose from $1.9 million to $2.8 million, driven by increases in professional fees and noncash share-based compensation.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) is still in the process of finalizing costs and timelines for Phase III trials, indicating potential uncertainties in future expenditures.
The company has not yet secured any commitments from potential partners for further development and commercialization of ibezapolstat, despite active discussions.
Q & A Highlights
Q: Bob, can you confirm the total number of subjects for the upcoming trial and clarify if the Phase IIb is considered one of the two pivotal studies required by the FDA? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - The total number of subjects for each of the two Phase III registration trials is 450, making it 900 in total. The Phase IIb is not considered a registration trial due to its small size. The upcoming trials are necessary to build a satisfactory safety database for an NDA application.
Q: Could you provide any preliminary information on the costs and timelines for the upcoming trials? Also, are there any active discussions regarding strategic partnerships? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We are currently finalizing the costs and timelines. Discussions about partnerships are active, especially now that we have a clear pathway for a pivotal study. We are engaging in several discussions, but nothing is finalized yet.
Q: When do you anticipate starting the first of the two Phase III trials? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We aim to start enrollment in the fourth quarter of this year, contingent on adequate funding. The enrollment is expected to take 18 to 24 months.
Q: Has the company considered applying for a priority review voucher for this application? A: Robert J. DeLuccia - Co-Founder & Executive Chairman, Acurx Pharmaceuticals, Inc. - We already have priority review due to our FDA fast track status. However, we are open to exploring the possibility of a priority review voucher, which could be a significant source of funding.
Q: Can you discuss the partnership environment as you approach Phase III? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - The environment is quite robust. We have a lot of interest from potential partners, and we are being judicious in our discussions to ensure we make the right deal without overly diluting our company.
Q: Is there an opportunity for any interim looks during the Phase III trials, and could you update us on the PASTEUR Act? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We do not plan to conduct interim looks as they require adding patients and do not provide significant insights. Regarding the PASTEUR Act, it is unlikely to pass this year, but we are monitoring potential funding opportunities for new classes of antibiotics through other government programs.
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
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>>> Psilocybin outperforms other treatments in easing depression in study
UPI News
5-2-24
by Dennis Thompson
HealthDay News
https://www.msn.com/en-us/health/other/psilocybin-outperforms-other-treatments-in-easing-depression-in-study/ar-AA1o2ppJ?OCID=BingNewsSerp
The active chemical in magic mushrooms could prove to be a powerful antidepressant, a new review finds.
Psilocybin outperformed a variety of "control" treatments in easing symptoms of depression, researchers reported Wednesday in the BMJ.
Those control groups received either placebo medications, the dietary supplement niacin (vitamin B), or microdoses of psychedelics.
"This review's findings on psilocybin's efficacy in reducing symptoms of depression are encouraging for its use in clinical practice as a drug intervention for patients with primary or secondary depression, particularly when combined with psychological support and administered in a supervised clinical environment," concluded the research team led by Athina-Marina Metaxa, a master's student with the University of Oxford's Department of Medicine in the U.K.
Depression affects an estimated 300 million people worldwide, an increase of nearly 20% over the past decade, researchers said in background notes.
Psilocybin has shown promise in reducing depression symptoms after one or two doses, with few side effects and no apparent risk of addiction, researchers said.
To provide an overview of where research now stands, a U.K. team examined data from seven clinical trials involving 436 people with depression.
Psilocybin provided a significantly greater change in depression scores than any of the control treatments, results show.
The treatment effects of psilocybin were significantly more powerful among patients who had depression alongside another mental illness, and when participants had previously used psychedelics, researchers found.
"Interestingly, a clear pattern emerged for past use of psychedelics -- the higher the proportion of study participants who had used psychedelics in the past, the higher the post-psilocybin treatment effect observed," the team wrote.
However, more evidence is needed to support psilocybin as an antidepressant, researchers said.
"Real-world" data is also needed, to assess both potential effectiveness as well as potential costs, researchers added.
Trial patients typically receive psilocybin in a calm living room with soothing music, under the supervision of a psychotherapist -- a situation unlikely to occur in typical healthcare settings.
"The combination of these elements makes this a relatively complex and expensive intervention, which could make it challenging to gain approval from regulatory agencies and to gain reimbursement from insurance companies and others," the researchers wrote.
"The high cost associated with the intervention also increases the risk that unregulated clinics may attempt to cut costs by making alterations to the protocol and the therapeutic process, which could have detrimental effects for patients," they added.
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>>> Simulations Plus (NASDAQ:SLP) is a leading modeling and simulation software provider for drug discovery and development. The company’s innovative software platform helps pharmaceutical and biotechnology companies accelerate the drug development process, reduce costs and improve success rates. Simulations Plus’ strong market position, expanding customer base and focus on innovation position are good for continued growth. The increasing complexity of drug discovery, the growing demand for efficient drug development processes and the rising adoption of computer-aided drug design are key megatrends that support Simulations Plus’ long-term prospects.
This is another stock in the healthcare industry sort of in the same boat as TCMD. Do not expect massive returns, but the possible gains are significant enough to include in a high-risk, high-reward basket of stocks. The company beat top-line estimates by nearly 6% in the recent quarter and has some of the best margin and cash positions, with negligible debt and $108 million in cash. Revenue growth is expected to be around 15% annually and 20-30% EPS growth going forward. However, you are paying a hefty premium for this stock, so I do not think life-changing returns are possible. However, it is still one of the AI stock picks worth buying for potential double-digit returns.
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https://finance.yahoo.com/news/ai-bot-predicts-7-stocks-175326496.html
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>>> Amgen, Inc. (NASDAQ:AMGN) - 14-day RSI: 37.92
https://finance.yahoo.com/news/11-oversold-blue-chip-stocks-195219274.html
Number of Hedge Fund Holders: 69
Thousand Oaks, California-based Amgen, Inc. (NASDAQ:AMGN) is a leading biotechnology company discovering, developing, manufacturing, and delivering innovative human therapeutics with a focus on areas of high unmet medical need.
On February 6, Amgen, Inc. (NASDAQ:AMGN) released its financial results for the Q4 2023. Its revenues increased by 20% y-o-y to $8.2 billion, while it generated a net income of $767 million. The normalized EPS for the quarter was recorded at $4.71, which surpassed the consensus by $0.12.
Earlier on October 6, 2023, Amgen, Inc. (NASDAQ:AMGN) completed the acquisition of Horizon Therapeutics plc in an all-cash transaction implying an equity value of nearly $27.8 billion. The acquisition strengthened the company’s inflammation portfolio by adding first-in-class, early-in-lifecycle medicines which treat rare inflammatory diseases.
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>>> Invivyd, Inc. (IVVD), a clinical-stage biopharmaceutical company, focuses on the discovery, development, and commercialization of antibody-based solutions for infectious diseases in the United States. The company's lead product candidate is adintrevimab, a neutralizing antibody that is in Phase 3 clinical trials for the treatment and prevention of coronavirus disease, as well as developing monoclonal antibody candidates, including VYD222 and VYD224, which provides neutralizing protection against SARS-CoV-2. It also has discovery stage candidates for the prevention of seasonal influenza. Invivyd, Inc. has a collaboration agreement with Adimab, LLC for the discovery and optimization of proprietary antibodies; and the Scripps Research Institute to perform research activities to identify vaccine candidates for the prevention, diagnosis or treatment of influenza or beta coronaviruses. The company was formerly known as Adagio Therapeutics, Inc. and changed its name to Invivyd, Inc. in September 2022. Invivyd, Inc. was incorporated in 2020 and is headquartered in Waltham, Massachusetts.
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https://finance.yahoo.com/quote/IVVD/profile
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>>> Regeneron Pharmaceuticals, Inc. (REGN) discovers, invents, develops, manufactures, and commercializes medicines for treating various diseases worldwide. The company's products include EYLEA injection to treat wet age-related macular degeneration and diabetic macular edema; myopic choroidal neovascularization; diabetic retinopathy; neovascular glaucoma; and retinopathy of prematurity. It also provides Dupixent injection to treat atopic dermatitis and asthma in adults and pediatrics; Libtayo injection to treat metastatic or locally advanced cutaneous squamous cell carcinoma; Praluent injection for heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in adults; REGEN-COV for covid-19; and Kevzara solution for treating rheumatoid arthritis in adults. In addition, the company offers Inmazeb injection for infection caused by Zaire ebolavirus; ARCALYST injection for cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome and muckle-wells syndrome; and ZALTRAP injection for intravenous infusion to treat metastatic colorectal cancer; and develops product candidates for treating patients with eye, allergic and inflammatory, cardiovascular and metabolic, infectious, and rare diseases; and cancer, pain, and hematologic conditions. The company was incorporated in 1988 and is headquartered in Tarrytown, New York.
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>>> FDA rejects Regeneron lymphoma drug, setting back company’s oncology push
Industry Dive
by Jonathan Gardner
March 25, 2024
https://finance.yahoo.com/news/fda-rejects-regeneron-lymphoma-drug-115500198.html
The Food and Drug Administration declined to approve an experimental lymphoma drug from Regeneron Pharmaceuticals, asking the company to first make more progress with a trial meant to confirm benefits observed in earlier testing, the company said Monday.
Regeneron said the FDA “did not identify any approvability issues” related to the safety, effectiveness or manufacturing of the drug, which is known as odronextamab. However, the agency wants to see study participants enrolled in the “dose finding” as well as “confirmatory” parts of an ongoing Phase 3 trial before it will issue a verdict, the company said.
Should it ultimately win approval, odronextamab would compete for market share with similar, “bispecific” drugs from AbbVie and Roche. Those drugs were greenlit in 2023 and posted sales of $17 million and $65 million, respectively.
Dive Insight:
Since cracking down on “dangling” accelerated approvals for cancer drugs – conditional clearances that weren’t confirmed through further testing – the FDA has been more hesitant to grant new ones. In Regeneron’s case, the drugmaker has been seeking a speedy approval in two types of lymphoma based on studies that measured remission rates but didn’t compare odronextamab’s performance to a placebo.
Accelerated approvals are conditional and granted on smaller trials that are “likely” to predict a benefit for drug recipients. But companies seeking them must back them up with bigger studies that prove those benefits by testing their therapies against a placebo or existing treatment.
Regeneron has already begun such a trial. However, the agency doesn’t believe Regeneron has made enough progress with enrollment yet, prompting a rejection. The FDA must also sign off on the timelines for the study’s completion before Regeneron resubmits its application. Regeneron will share updates later this year, it said in a statement.
Odronextamab is a type of dual-pronged antibody drug that’s become increasingly popular in recent years. It binds to the same targets on immune and malignant cells as AbbVie’s Epkinly and Roche’s Columvi, both of which won accelerated approvals in B cell lymphomas.
In a research note Monday, Sean McCutcheon, an analyst with Raymond James, wrote that he expects an agreement between Regeneron and the FDA once the “confirmatory” portions of the study begin. Still, the setback represents a missed opportunity for Regeneron, which has struggled to compete with more established players in oncology.
“We continue to see odronextamab as a modest opportunity given competitive headwinds, with the delay as a further hurdle to garnering market share,” he wrote. “The [rejection] also further adds to investor pessimism on the company’s execution within oncology.”
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>>> Cardiff Oncology Announces Upcoming Presentations at the AACR Annual Meeting 2024
Cardiff Oncology, Inc.
March 6, 2024
https://finance.yahoo.com/news/cardiff-oncology-announces-upcoming-presentations-210500325.html
SAN DIEGO, March 06, 2024 (GLOBE NEWSWIRE) -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced publications of five abstracts that will be presented in a poster session at the American Association for Cancer Research (AACR) Annual Meeting, taking place from April 5-10, 2024, in San Diego, California.
“The posters we will be presenting at this year’s AACR meeting represent a broad view of the potential of onvansertib in several different cancer indications, including RAS-mutant mCRC, RAS-wild type mCRC, small cell lung cancer and ovarian cancer,” said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. “In RAS-mutated mCRC, we are showing the underlying mechanism through which the combination of onvansertib and bevacizumab targets the hypoxia response pathway. We believe this mechanism explains the strong clinical results we have seen in both our Phase 1b/2 and ONSEMBLE second-line RAS-mutated mCRC clinical trials. The additional posters provide new insights and rationale for future clinical trials in other cancer indications.”
Details on the posters and corresponding abstracts are shown below.
Poster Title: A phase 1b/2 clinical study of onvansertib in combination with FOLFIRI/bevacizumab revealed a new role of PLK1 in regulating the hypoxia pathway in KRAS-mutant colorectal cancer
Session Title: Microenvironment, Immunity, and DNA Repair in Therapeutic Response
Session Date and Time: Monday Apr 8, 2024: 9:00 AM - 12:30 PM PT
Location: Poster Section 27, Poster Board #14, Abstract Number #2031
This abstract presents updated clinical data and biomarker analysis from the Phase 1b/2 study evaluating onvansertib in combination with FOLFIRI/bevacizumab for second-line treatment of KRAS-mutant metastatic colorectal cancer (mCRC) patients. Analysis of patient baseline characteristics revealed superior clinical benefit in patients not exposed to bevacizumab in first-line treatment (Bev-naïve) compared to Bev-exposed patients. Bev-naive patients exhibited higher objective response rates (73.3% versus 15.7%) and longer median progression-free survival (14.9 versus 7.8 months) compared to Bev-exposed patients. Preclinical studies, using KRAS-mutant colorectal cancer mouse models revealed robust antitumor activity of onvansertib in combination with bevacizumab and a novel role of onvansertib in regulating tumor vascularization. Further preclinical investigations showed that PLK1 regulates the hypoxia pathway in KRAS-mutant CRC cells through the modulation of the hypoxia-inducible factor 1 alpha, HIF1a, emphasizing the potential crosstalk between PLK1 and angiogenesis. These findings reinforce the rationale for exploring onvansertib in combination with FOLFIRI/bevacizumab for Bev-naïve mCRC patients with KRAS mutation.
Poster Title: The PLK1 inhibitor, onvansertib, is active as monotherapy and in combination with cetuximab in RAS wild-type colorectal cancer patient-derived xenografts
Session Title: Drug Resistance 2: Ras GTPase
Session Date and Time: Monday Apr 8, 2024: 9:00 AM - 12:30 PM PT
Location: Poster Section 24, Poster Board #12, Abstract Number #1934
This abstract focuses on the preclinical assessment of onvansertib’s antitumor activity in RAS wild-type colorectal cancer, as both a monotherapy and in combination with cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Employing patient-derived xenograft (PDX) models, the study highlights the robust antitumor efficacy of onvansertib monotherapy, in cetuximab-sensitive and -resistant RAS wild-type colorectal cancer models. Furthermore, the combination of onvansertib and cetuximab was highly effective, resulting in tumor regression in 90% of the PDXs. These compelling data strongly support the clinical development of onvansertib as a potential treatment for RAS wild-type colorectal cancer.
Poster Title: A phase 2, randomized, open-label study of onvansertib in combination with standard-of-care (SoC) versus SoC alone for first-line treatment of RAS-mutant metastatic colorectal cancer(mCRC)
Session Title: Phase II and Phase III Clinical Trials in Progress
Session Date and Time: Tuesday, Apr 9, 2024: 1:30 PM - 5:00 PM PT
Location: Poster Section 50, Poster Board #5, Abstract Number #CT275
This abstract describes a clinical trial in progress.
Poster Title: The PLK1 inhibitor, onvansertib, synergizes with paclitaxel in small cell lung cancer
Session Title: Kinase and Phosphatase Inhibitors 1
Session Date and Time: Sunday Apr 7, 2024: 1:30 PM - 5:00 PM PT
Location: Poster Section 25, Poster Board #16, Abstract Number #606
This abstract outlines preclinical studies showing the promising potential of combining onvansertib with paclitaxel for small cell lung cancer (SCLC). The research reveals significant synergy of the combination in SCLC cell lines and demonstrates its robust antitumor activity in patient-derived xenograft models, including models resistant to the standard therapy cisplatin. Further insights into the combination's mechanism of action will be presented. These findings support that combining onvansertib with paclitaxel could emerge as a highly promising treatment strategy for SCLC.
Poster Title: In vivo anti-tumor activity of onvansertib, a PLK1 inhibitor, combined with gemcitabine or carboplatin in platinum-resistant ovarian carcinoma patient-derived xenograft models
Session Title: Application of Precision Medicine for Cancer Care
Session Date and Time: Sunday Apr 7, 2024: 1:30 PM - 5:00 PM PT
Location: Poster Section 39, Poster Board #13, Abstract Number #945
This abstract explores preclinically the potential of combining onvansertib with the chemotherapeutic agents carboplatin or gemcitabine for platinum-resistant high-grade ovarian carcinoma. Using patient-derived xenografts, we demonstrated robust efficacy for both combinations, coupled with favorable tolerability. These data underscore the potential of onvansertib to improve the efficacy of the standard-of-care carboplatin and gemcitabine for patients with platinum-resistant high-grade ovarian carcinoma.
The abstracts are available on the AACR Online Program and will be published in the online Proceedings of the AACR. Following presentation, the posters will be posted to the "Scientific Presentations" section of the Cardiff Oncology website.
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 small cell lung cancer (SCLC) and triple negative breast cancer (TNBC). 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.
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>>> Acurx Pharmaceuticals, Inc. (NASDAQ:ACXP) Q4 2023 Earnings Call Transcript
Published March 19, 2024
by INSIDER MONKEY TRANSCRIPTS
https://www.insidermonkey.com/blog/acurx-pharmaceuticals-inc-nasdaqacxp-q4-2023-earnings-call-transcript-1276747/#q-and-a-session
Acurx Pharmaceuticals, Inc. (NASDAQ:ACXP) Q4 2023 Earnings Call Transcript March 18, 2024
Operator: Greetings and welcome to the Acurx Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Earnings Results and Business Update Call. At this time, all participants are in a listen only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the call over to your host, Robert Shawah, Chief Financial Officer for Acurx Pharmaceuticals. Thank you. You may begin.
Robert Shawah : Thank you, Melissa. Good morning, and welcome to our call. This morning we issued a press release providing financial results and company highlights for the fourth quarter and full year 2023, which is available on our website at acurxpharma.com. Joining me today is David Luci, President and CEO of Acurx; as well as Robert DeLuccia, Executive Chairman. David will give a corporate update and outlook. After that, I’ll provide some highlights of the financials from the quarter and year end of December 31, 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. 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 annual report on Form 10-K, which we filed on Friday, March 15, 2024. You are cautioned not to place undue reliance on these forward-looking statements and Acurx disclaims any obligations 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, March 18, 2024. 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 fourth quarter of 2023 and also to hear some very exciting recent updates. Then we’d be pleased to take any questions. First, I’ll summarize some of our key activities for the fourth quarter of ‘23 or in some cases shortly thereafter. On October 2, 2023, we ended enrollment in our Phase IIb clinical trial of ibezapolstat or IBEZ, 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 IIb clinical trial including overall results from the full Phase II study, demonstrating and ibezapolstat clinical cure rate at end 10 days oral treatment or EOT of 96%, 25 of 26 patients, which included 100% cure in Phase IIa and 94% cure in Phase IIb compared with vancomycin control arm the standard of which was 14 for 14 or a 100% at end of treatment and 94% was sustained cures.
No safety concerns were reported in either arm of the Phase IIb clinical trial and ibezapolstat was well tolerated in all patients in both the Phase IIa open-label trial and the Phase IIb vancomycin control segment. In consultation with our scientific advisors, the company determined that based on review of aggregate blinded data, the Phase IIb vancomycin control trial segment was terminated early due to success showing high observed clinical cure rates with no emerging safety concerns, clinical comparability was established. We also stated at that further data would be provided as it becomes available on secondary and exploratory endpoints for the Phase IIb trial segment, including sustained clinical cure data at 30 days after EOT and extended clinical cure data 94 days after EOT as well as comparative data on the impact on the patient’s microbiome.
On December 11 ‘23, we announced the sustained clinical cure data. These data showed that in the Phase IIb trial segment 100% or 15 out of 15 of our advantaged patients who were cured at EOT remained cured with no reinfection 30 days later, while vancomycin experienced a reinfection rate of 14.3%, 2 of 14 patients were reinfected.
On January 17, 2024, we announced positive comparative microbiology and microbiome data for the ibezapolstat in CDI patients from the Phase IIb clinical trial segment. Ibezapolstat to outperformed vancomycin showing eradication of fecal C. difficile at day three of treatment in 15 of 16 treated patients versus vancomycin, which had eradication of fecal C. difficile in just 10 of 14 treated patients. Additional data from the Phase IIb clinical trial showed ibezapolstat but not vancomycin consistently observed and allowed regrowth of key gut bacterial species believed to confer health benefits including prevention of recurrent C.difficile infection.
We anticipate that additional data from the secondary and exploratory endpoint will provide further favorable separation these two therapeutic options in our Phase III clinical trial program and ultimately in the marketplace if approved. Additional analysis, regarding other secondary and exploratory endpoints will be forthcoming as data become available. We remain particularly excited about the dual impact of ibezapolstat to treat acute C. difficile infection while appropriately managing the long-term care of each patient’s microbiome, which we believe is exceptional for antibiotic therapy. Having robust preclinical — clinical and manufacturing data to date, we submitted a formidable information package in early February to FDA along with a request for an end of Phase II meeting, which was granted by FDA on Feb 26, and is scheduled to occur in April.
We anticipate discussing our Phase III clinical trial mandate at this meeting and would anticipate documented meeting minutes from FDA sometime in the second quarter this year. We also announced that the European Medicines Agency approved their application to be designated as a small to medium sized enterprise or SME in Europe, which provides for certain benefits including fee reductions and other support from the European Medicines Agency for seeking a marketing authorization in Europe. In November, 2023, we filed an amendment to our shelf registration statement with the Securities and Exchange Commission and put up a $17 million at the market or ATM facility with Alliance Global Partners acting as sales agent to the company. Proceeds from the ATM will be used for general corporate purposes going forward, including our plan Phase III clinical trial mandate.
In October, 2023, at ID Week, Dr. Kevin Garey presented on our behalf with selective spectrum of activity data from our Phase IIa clinical trial. Many of you may recall, Dr. Gary is Professor and Chair University of Houston, College of Pharmacy and the Principal Investigator for our microbiome aspects of the ibezapolstat clinical trial program. Also at ID Week, Bob DeLuccia, our Executive Chairman, presented our new class of novel DNA pol IIIC inhibitors in our preclinical pipeline at the symposium entitled new antimicrobes in the pipeline. Now that’s a lot of activity to digest. So I’ll summarize further as to where we are today. As we speak, we’re preparing to advance ibezapolstat into Phase III clinical trials and anticipate a favorable outcome from our upcoming FDA meeting regarding readiness to proceed and also to obtain agreement on the regulatory pathway for a new drug application filing for marketing approval in the U.S. once Phase III is completed.
We’ve also officially started the regulatory process in Europe will add other territories to the list later this year. The Phase III trials will include U.S. and international sites to enhance overall enrollment and to support international regulatory filings for marketing approval. This will save us a lot of time and money and allow us to expand our ultimate commercial reach. To ensure Phase III clinical trial and enrollment as quickly as possible, we’re adding substantially more clinical trial sites, way above the number we used to conduct our U.S.-only Phase II trials. We’re now getting our arms around the costs and time lines, but our plan is to conduct the required two Phase III registration trials consecutively not concurrently given the size of our company and need to use our financial resources most efficiently.
The time line for conduct of our Phase III trial is not a concern since ibezapolstat will have a rolling 10 years of regulatory exclusivity in the U.S. from the FDA approval date with similar legislation in Europe, the U.K. and Japan. We will continue to seek strategic transaction for the company, including a potential partner for the further development and potential commercialization of ibezapolstat as well as a potential sale merger third-party ex U.S. territorial or licensing arrangement or our strategic transaction alongside in parallel with our preparation for Phase III clinical trials. At this time, we have no commitments from potential partners or others to provide the company with capital, but we started this initiative only recently in February after our Phase IIb data was released.
So basically, we have two formidable plans going forward, and we’re equally excited about partnering M&A and Phase III enrollment as next steps over the next 12 months. As we’ve consistently reported, ibezapolstat continues to outperform in a series of potentially life-threatening infectious disease called C. difficile that the U.S. CDC categorizes as an urgent threat and there’s a need for new classes of antibiotics for initial treatment but also has a low incidence of recurrence. Ibezapolstat also has FDA Fast Track designation for treatment of C. difficile infection. Additionally, we believe ibezapolstat, if approved, could make a favorable impact by reducing the cost burden of current C. difficile infection in our U.S. health care system, which is estimated at $4.7 billion annually.
We do believe the best is yet to come. And now back to our CFO, Rob Shawah to guide you through the highlights of our financial results for the fourth quarter and full year 2023. Rob?
Robert Shawah : Thanks, Dave. Our financial results for the fourth quarter and 12 months ended December 31, 2023, were included in our press release issued earlier this morning. The company ended the year with cash totaling $7.5 million compared to $9.1 million as of December 31, 2022. Subsequent to year-end, the company sold an additional 1,121,793 shares under its ATM financing program with gross proceeds of approximately $4.5 million. Research and development expenses for the three months ended December 31, 2023, were $1.9 million compared to $1.4 million for the three months ended December 31, 2022. The increase was due to timing of Phase IIb trial related costs and an increase in consulting costs. For the year ended December 31, 2023, research and development expenses were $6 million, which is $4.8 million for the year ended December 31, 2022.
The increase to due primarily the Phase IIb costs and an increase in consulting costs. General and administrative expenses for three months ended December 31, 2023 were $3.2 million compared to $1.8 million, where the three months ended December 31, 2022. The increase was due primarily to $800,000 increase in professional fees, a $0.1 million increase in share based compensation and a $0.3 million increase in employee compensation costs. For the year ended December 31, 2023, general and administrative expenses were $8.5 million versus $7.3 million for the year ended December 31, 2022. The amounts reflect an increase in professional fees of $0.5 million, an increase of $0.3 million in share based compensation and an increase of $0.3 million in employee compensation costs.
The company reported a net loss of $5.1 million or $0.37 per diluted share for a three months ended December 31, 2023, compared to an net loss of $3.3 million or $0.28 per diluted share for the three months ended December 31, 2022, and the net loss of $14.6 million or $1.15 per share for the year ended December 31, 2023 compared to a net loss of $12.1 million or $1.12 per diluted share for the year ended December 31, 2022, the reasons previously mentioned. The company had 14,468,229 shares outstanding as of December 31, 2023. With that, I’ll turn the call back over to Dave.
David Luci : Thanks Rob, and to all of you for joining us today. I’ll now ask Bob DeLuccia our Executive Chairman to provide his perspective given Bob manages our R&D program and when Bob is finished, operator, please open the call for questions. Bob?
Robert DeLuccia : Thanks Dave and Rob for updating our stakeholders and thanks to all for the continuing support as we advance ibezapolstat into Phase III clinical trials. It is a very exciting time and really it’s the final step to commercialize ibezapolstat for patients in need of a promising new antibiotic with a novel bactericidal mechanism of action to treat CDI, and many of you will remember that approximately 30,000 people die each year in the U.S. alone from CDI and the annual incidence is more than about 500,000 per year in the United States. But the bottom line here is that if the outcome of our Phase III trials are consistent with our Phase II experience, we’ll have an approvable new drug in our hands. The data are solid, the market is large and our manufacturing cost is low.
We do have a robust preclinical — clinical microbiome safety and CMC evidence package that we’ve submitted to the FDA and as Dave mentioned, they’ve determined it acceptable to grant us an end of Phase II meeting next month to discuss trial design, patient enrollment targets and to confirm our readiness to go forward. So to complete our Phase II international Phase III trials, which will be done sequentially as Dave mentioned and as quickly as possible, we’ve already initiated steps to advance screen potential clinical trial sites, which in addition to North America will cover sites in about 17 other countries, including several in Eastern Central, Northern and Western Europe, totaling about 100 sites, which we believe will accelerate overall enrollment.
We’ll also be including several high enrolling trial sites from the fast enrolling Summit Phase III CDI trial, which was conducted during the height of COVID-19. In addition to global scope of the program compared to Phase II and the strength of our Phase II data, the Phase III protocol will allow more flexibility for inclusion and exclusion criteria as a standard for CDI pivotal registration trials. So we anticipate faster enrollment. Then once we have results from our FDA meeting and documented meeting minutes from the FDA, our next priority will be to submit our plans to the European Medicines Agency or EMA for conducting Phase III clinical trials in Europe. So if approved, we’ll have the first new class of antibiotics approved by FDA in over 30 years with only confirmatory Phase III trials between now and market introduction.
Ibezapolstat as Dave mentioned is fast tracked by FDA, it’s fully patented and with regulatory exclusivity 10 years post-market introduction in the U.S. and similar opportunities for regulatory exclusivity in other geographies to pursue at the appropriate time. And also with recent focus on minimizing effects on the microbiome to lower recurrence of infection, we stand out from other antibiotics since we’ve shown no reinfection in Phase III patients (note - I think he meant Phase 2) who were initially cured of their infection. So in my over 50 years of experience in antibiotic development and marketing. I think, I have got a great rear view mirror and a clear vision to say that we have a winner here for patients with CDI and in general for better public health as well as for our shareholders.
Thanks for letting me comment, Dave.
Robert Shawah : Thank you, Bob. Melissa, we’re now ready to go to Q&A.
Operator: [Operator Instructions] First question is from the line of Jason McCarthy with Maxim Group.
Michael Okunewitch: This is Michael Okunewithch for Jason. I guess to start off, I’d like to see if you could give an idea of what sort of time line you are expecting between getting those meeting minutes back from the FDA and actually launching the first of those Phase III studies?
David Luci: So we think that we will be ready to enroll the first patient in for the international Phase III in the fourth quarter of this year.
Michael Okunewitch: And then, I guess, regarding the international component to the study, could you talk a little bit more about the path to actually getting those sites online? And is this something that you would look to have in place ahead of the launch? Or would you start with what do you have when you usually enroll the study like you are in these international sites as they were approved?
David Luci: We will be a little bit on both. We have a number of the sites already kind of ready to go from the international list. There won’t be any hold up from the international aspect of it. We actually have a consultant who is extremely familiar with Phase III C. diff international trials who’s been guiding us in this regard. But yes, clearly, when our manufactured product is ready, we’ll be ready to go with a large wedge at the very least of the hundred sites.
Michael Okunewitch: And then one last one from me, and I’ll hop back in the queue. With regards to securing international partnerships, do you think this is something with your existing body of data that is compelling enough that you could really progress those conversations now and get a partner or would you expect it to be more after you get that first slot of Phase III data?
David Luci: No, I would expect that the prime time for us to find, I’d say a European partner or a Japanese partner would be — when we start enrolling the first of the two Phase III trials, once we have the Phase III trial mandate completed and we’re ready to find or to file a new drug application, if we haven’t had a partnership by then, I think it would probably not occur until a year after the market introduction, because folks will want to see how well we do. I think that the time is right now. I’ll make one additional comment on the territorial partnerships to carry Michael’s question response a little bit further. As we look at strategic alternatives, there’s M&A full stop and there’s territorial licensing and co-development agreements that I have entered into in the past.
With our share price being where it is, the territorial licensing is a bit easier to consummate because it’s all about the intrinsic value of your drug as opposed to M&A, which you can’t in my view, wholly divorce yourself of your NASDAQ share price. So it may be a more attractive option for our board of directors and but we’ll see what term sheets present themselves.
Operator: Our next question comes from the line of James Molloy with Alliance Global Partners.
James Molloy : The Phase III trials, I know that obviously a lot to go here, but can you walk through expectation which we should expect to see coming out of the end of Phase II? And then the trial designed to sort of the length of time to run is about two years start to finish. So Phase IIb, I know we we’re dealing with COVID then as well. Is that seem reasonable to run these two Phase IIIs from start to finish?
David Luci: So we’re going to address one Phase III and then the idea would be to either do a strategic transaction after that first Phase III or with positive data on the first Phase III, if it’s the same or consistent with our Phase II, get a share price rise and then raise capital for the second Phase III. So we’re targeting a year and a half from start to finish for the first Phase III, and that would have us completing the first Phase III in the second quarter of ‘26. Now I can tell you that we spent a lot of time looking at the Summit Therapeutics experience and Summit enrolled in the teeth of COVID, 750 or so patients in about two years time largely in Eastern Europe, where the behavior patterns weren’t dramatically changed apparently, like they were here in the U.S. So, that’s a public list on clinicaltrial.gov.
So we were able to see exactly the heat patterns from their enrollment. So that’s gone a long way to helping us get comfortable with fixing the enrollment issues we had during COVID with our U.S. only trial.
James Molloy : I thought I’d heard you say earlier in the call that you’re going to run the two trials at the same time obviously misheard that, you’re running back to back.
David Luci: No. Our going in plan is to do them consecutively instead of concurrently for the financial reasons that we discussed. But if we get a partnership, say a European licensing agreement and that brings in and enough money to call an audible along the way and at that point then we would certainly start the second Phase III accordingly.
Operator: [Operator Instructions] Our next question comes from the line of Ed Arce with H.C. Wainwright.
Ed Arce : So a couple from me, firstly on the end of Phase II next month and I apologize I joined late, so maybe you went over this already, but wanted to make sure to review sort of the key objectives in particular what do you not have agreement with the agency yet on that you would seek to get agreement on next month in that meeting? And then secondly, I think you made mention of a wider inclusion exclusion criteria for the Phase III relative to the prior Phase II. And so just wanted to get a little more clarity on that in particular that a view to concerns there might be around the risk that you could change the sort of design of the trial and there could be some disruption from a slightly different patient population.
David Luci: Thank you, Ed. I’ll answer the first part of your question and ask Bob to provide a response for the inclusion and exclusion criteria part of your question. So for the first part of your question, what we hope to agree on with the FDA is the overall protocol designed for our Phase III trial, including the number of patients to be enrolled the notion that we’re going to have a vancomycin control arm like we had in our Phase IIb. Largely, the trial design is 90% plus of what the trail design was for our Phase IIb. So we don’t expect a real lot of drama, but it’s a necessary step in order to kind of be allow to into Phase III, so we’re looking forward to our valuation point that we have to get through. Bob, did you want to add some comment on the inclusion and exclusion criteria?
Robert DeLuccia: I think really two things, which is standard fair for going forward in Phase III is that we’ll have additional patients beyond mild and moderate that are included in the trial. So this is not severe CDI, but a little bit more than moderate according to the IDSA criteria for patient entry into a trial in the study. So we’ve already submitted a framework to the FDA in the meeting package. It’s very straightforward. I’d even say a higher percentage that they’ve said at 90%. We’re pretty much there with the design. It’s the same design basically, it’s Phase II and very standard according to the FDA guidance from October 2022, I believe it is, as to what needs to be included in the Phase III clinical trials. So we’ll be discussing final numbers of patients, as I said before and statistical analysis plan will be finalized at that upcoming FDA meeting as well. Anything else? Does that answer your question?
Ed Arce: Yes, that’s helpful.
Operator: Thank you. Ladies and gentlemen, that concludes our question-and-answer session. And this concludes our call today. We thank you for your interest and participation. You may now disconnect your lines.
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The FDA approved Amarin’s CVD risk-reducing drug, Vascepa, in 2019, having first approved it for triglyceride reduction in 2012. At a cost less than $60/year under my insurance plan, I began taking oral Vascepa capsules, off-label, with prescription in April 2013 at age 76(father died from 2nd heart attack at age 51 in 1959). Never obese, I have lost about 25 lbs while using 20% less LLY insulin to manage my T1-D since 2016. I now weigh the same as I did in my university years, 1955-1961.
PFE sells Vascepa in all Canadian provinces, per agreement.
AMRN’s share price, $0.90, is about even YTD. Share price was $18-25 in 2019. Shareholders will vote on a share repurchase plan in early April 2024 while waiting for revenue-driven earnings from Europe and Asia, and results from the Brave trial (Indication: Alzheimer’s ). Sarissa Capital holds ~ 9.9% of outstanding shares, and views Amarin as under-valued. Will AMRN share price out-perform share price of either LLY or NVO in 2024-2025 in % gain?
Orchard Therapeutics - >>> A lifesaving therapy for children with a rare disease is now the world’s most expensive drug, raising questions about access
CNN
by Brenda Goodman
March 20, 2024
https://www.yahoo.com/lifestyle/fda-approved-lifesaving-therapy-children-194412723.html
A new gene therapy for the fatal genetic disorder metachromatic leukodystrophy, or MLD, will carry a wholesale price of $4.25 million, its manufacturer announced Wednesday, making it the world’s most expensive medicine.
Lenmeldy was approved by the US Food and Drug Administration on Monday and is the first therapy for the rare and devastating disease, which typically kills affected children before they turn 7. About 40 children are born with MLD in the US each year.
The wholesale cost isn’t usually what patients pay, but it’s a cost that’s considered and shouldered by public and private health insurance plans, including state Medicaid plans, which cover roughly 4 out of every 10 children in the United States.
Manufacturers of gene therapies say the big prices reflect big benefits — the chance to be free of a disabling or even fatal disease — and they point out that they need to be able to recoup the steep costs of development, testing and manufacturing their products.
Health policy experts say that as the list of gene and cell therapies with eye-popping prices grows, it may strain the ability of states and other insurers to cover their costs, and ultimately limit patient access if plans begin to exclude these therapies as a class from coverage.
Dr. Bobby Gaspar, the co-founder and CEO of Orchard Therapeutics, the company that makes Lenmeldy, said the treatment is “paradigm-shifting medicine and has the potential to stop or slow the progression of this devastating childhood disease with a single treatment.”
“We are committed to enabling broad, expedient and sustainable access to this important therapy for eligible patients with early-onset MLD in the U.S.,” Gaspar said in a statement.
Price of hope
Lenmeldy takes stem cells from someone with MLD and uses a harmless virus to insert working copies of a faulty gene. The repaired cells are then infused back to the patient, where they begin to produce an enzyme that’s lacking in children who have the disease. Some of the cells eventually migrate to the bone marrow, where they continue to live and make new cells that also make the enzyme, providing a long-lasting benefit to patients.
The first patients treated with Lenmeldy have now been followed for more than 12 years, and researchers continue to find gene-modified cells making the missing enzyme, said Orchard Therapeutics’ Gaspar.
“We can’t say at the moment that this will last a lifetime, but what we can say is that there is a longterm durable effect,” Gaspar said.
MLD is an inherited disorder, and children born with it lack an enzyme needed break down fatty substances called sulfatides. The build-up of these fatty materials eventually becomes toxic to nerves, leading to the progressive loss of movement and thinking.
Babies with MLD develop normally for a time and but then typically begin to lose the ability to walk and talk around age 2. The disease advances rapidly, causing children to deteriorate into a vegetative state.
“We are over the moon regarding what this means for other families,” said Kendra Riley, 41, of Phoenix, who has two children with MLD.
For their family, the FDA’s action this week was bittersweet.
Riley’s 5-year-old daughter, Olivia, is in hospice after being diagnosed with MLD as a toddler.
Riley says the first clues that something was wrong came when Olivia was around the age of 2. She began to have trouble walking, and her head started to regularly tilt to the side when she would watch TV.
“We thought we just needed some physical therapy,” Riley said.
“Then the irises of her eyes started vibrating. That’s when we knew something else was going on.”
By the time doctors diagnosed Olivia with MLD, it was too late for the gene therapy to help. But knowing that the condition is inherited, they were able to get their younger daughter, Keira, tested and diagnosed.
Keira, now 4, was the 32nd child in the world to get the therapy, which is most effective before children show symptoms.
The treatment wasn’t yet available in the United States, so the family crowdsourced donations to temporarily relocate to Italy in 2020 to get the therapy. It cost them about $500,000 to live abroad and pay for Keira’s medical care, even though the company provided the gene therapy for free.
“Having this FDA-approved therapy means that if a child does get diagnosed before symptom onset, they have a chance at normal life,” Riley said.
“She is doing amazing. Zero symptoms,” she said of Keira. “You would never know.”
‘Exciting’ drug development
The Boston nonprofit Institute for Clinical and Economic Review, or ICER, which evaluates the cost effectiveness of new drugs, published a final report on Lenmeldy last fall and estimated that the cost of the therapy would match its expected benefits to patients if it was priced between $2.3 million and $3.9 million.
Experts agreed that even such hefty price tag would be worth its results. Children with the disease who aren’t treated usually die within five years of their diagnosis; the oldest patient to have the therapy has now been followed for more than 12 years and appears to be developing normally.
“It’s taking a child who would have had a miserable short life and likely giving them a normal life. And that’s worth a lot of money,” said Dr. David Rind, the chief medical officer for ICER. “This is one of the more exciting drugs that we’ve looked at.”
Still, the Lenmeldy’s price came in hundreds of thousands of dollars higher that even Rind expected.
“I think when you get into numbers this big that people don’t necessarily pay attention when it gets a little bigger, but I do think this price is too high,” Rind said.
ICER gave a range of $2.29 million to $3.94 million — that doesn’t mean that the top of the range is the right price, said Rind “despite the desire by manufacturers to think of it that way.”
“Going $310,000 above the very top of that range is actually a lot of money,” he said.
The last product to top the charts on a per-treatment basis was another gene therapy called Hemgenix, which was approved in 2022 to treat a blood clotting disorder called hemophilia B. Its list price was $3.5 million for a one-time treatment.
Close behind that one is Elvevidys, which was approved in 2023 for muscular dystrophy at $3.2 million, and Skysona, approved in 2022 for a disease related to MLD called adrenoleukodystrophy, which costs $3 million for a one-time dose.
Even with a top tier price, the MLD treatment will not be a blockbuster, Rind noted, because the disease is so rare. Some gene therapies approved for rare diseases have disappeared because the companies that made them couldn’t make enough money to stay in business. Orchard Therapeutics has already struggled to market a previous gene therapy it developed, leaving patients hanging.
Edwin Park, a research professor at the McCourt School of Public Health at Georgetown University, worries about the impact to states, which share the cost of covering patients on Medicaid with the federal government.
Medicaid requires a minimum rebate from drug manufacturers, but without any competition, there probably won’t be much negotiation about the price of the therapy, Park said.
More and more states are closely following drug pipelines after being surprised by the costs of the antiviral medications that cure hepatitis C, he said.
But even paying for one or two children to get Lenmeldy a year could be a sizeable cost for some states to absorb.
“Unless states have allocated appropriately for it, and looked at the drug pipeline, they may not be prepared for what could be significant cost spikes,” Park said.
New possibilities for patients
This latest approval comes as the FDA is working to clear a backlog of cell and gene therapies that have been waiting for its attention since the pandemic. The agency has hired more staff to review the new treatments and set up a new superoffice, the Office of Therapeutic Products, to oversee their regulation.
Lenmeldy has been available in Europe since 2020, but it took four more years to bring it to the US.
Dr. Nicole Verdun, who was hired to head the new FDA initiative last year, said Lenmeldy’s approval is a sign that things are moving in the right direction.
“MLD is a devastating disease that profoundly affects the quality of life of patients and their families,” Verdun said.
“This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.”
Dr. Barbara Burton, who is an attending physician, of genetics, genomics and metabolism at the Ann & Robert H. Lurie Children’s Hospital of Chicago, said it was a watershed moment for doctors, too.
“For too long, my colleagues and I have consoled families at their most vulnerable times — usually following an arduous diagnostic odyssey, coping with a dire prognosis and being told there were no treatments, and then having to watch their young child slip away.
“With this approval, we are now one significant step closer to ensuring future generations of children, families and healthcare professionals no longer need to experience first-hand the terrible manifestations this disease has on untreated patients,” she said.
The approval of a treatment is already leading to new ways to catch the disease earlier.
Gaspar, of Orchard Therapeutics, noted that the company was supporting studies of newborn screening tests in the hopes of catching and treating the condition earlier, and screening is happening in some US states.
“Over 250,000 babies have been screened them as a result of these initiatives,” Gaspar said, and five babies with MLD have been identified. At least three of those babies have now been treated.
Riley said she wishes screening had been available for Olivia. The 5-year-old is stable for now, but Riley said she lives in fear that Keira could bring germs home.
“The common cold could kill her,” Riley said. “So every time her sister has come home with a cold from school, that could be potentially something that takes her out.”
Olivia can’t walk or talk, and she’s fed through a tube. Riley says she requires round-the-clock care. Physical and occupational therapists come to the house each week “to keep her mind moving. She does understand what’s going on.”
She said that as they have watched Olivia slip away, they’ve come to understand that her life has had profound purpose. But they say they hope that the approval of Lenmeldy means that no other families with MLD will have to lose one child to save another.
“We’ve always called Livvy ‘Keira’s guardian angel on Earth,’ ” Riley said. “She’s here for a reason.”
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>>> Will Novo Nordisk Overtake Eli Lilly as the Most Valuable Healthcare Stock?
David Jagielski
Motley Fool
March 20, 2024
https://finance.yahoo.com/news/novo-nordisk-overtake-eli-lilly-123000972.html
Novo Nordisk (NYSE: NVO) and Eli Lilly (NYSE: LLY) are the top two healthcare stocks in the world based on market cap. Their diabetes and weight loss medications are a big reason these have been among the best healthcare investments to own over the past few years. Today, Eli Lilly is the larger of the two companies, with a market cap of more than $700 billion. Novo Nordisk, however, isn't too far behind, sporting a valuation about $600 billion. And there are some recent catalysts that suggest that gap could shrink in the future.
Why Novo Nordisk could soar higher this year
Novo Nordisk stock is up 28% so far in 2024, and there are a couple of reasons it may become an even hotter in the weeks and months ahead.
On March 8, the Food and Drug Administration approved Novo Nordisk's weight loss treatment, Wegovy, for a new indication: reducing cardiovascular risk in obese or overweight adults. Up until then, the drug was only approved as a treatment for weight loss. The label expansion gives patients another reason to use the drug, which could result in more prescriptions and insurance coverage -- and thus, more revenue.
Novo Nordisk has also been working on a weight loss pill (Wegovy is an injectable) that has been demonstrating encouraging results in clinical trials, showing that it can achieve faster weight loss than Wegovy: 13% after 12 weeks versus just 6% with the injectable treatment. It was an early-stage trial but the data is promising nonetheless.
In 2023, Novo Nordisk's sales increased by 36% (when excluding the impact of foreign exchange) to 232.3 billion Danish kroner ($34.8 billion). Wegovy's sales of 31.3 billion Danish kroner soared by a staggering 420%. And with much more potential on the horizon with a new indication for Wegovy and it entering new markets, Novo Nordisk is nowhere near done growing. Having a weight loss pill in development that could be even better than Wegovy gives investors even more reason to stay bullish on the stock for the long haul.
Could Eli Lilly's stock struggle?
Novo Nordisk is more of a pure-play weight loss and diabetes investment, whereas Eli Lilly's business is much more diversified. And that diversification is one of the reasons the healthcare stock may stumble a bit this year. Recently, regulators delayed making a decision on Eli Lilly's Alzheimer's treatment, donanemab. While it's likely to still obtain approval, the stock fell on the news.
In addition to diabetes treatments, Eli Lilly's top five treatments for the last three months of 2023 featured a breast cancer drug (Verzenio) and psoriasis medication (Taltz). While weight loss is a big growth opportunity for Eli Lilly, with recently approved Zepbound just starting to generate revenue for the business, its operations are certainly broader than Novo Nordisk's.
Another reason the healthcare stock could face pressure this year is that it trades at a lofty 60 times forward earnings, which is based on analyst expectations of where its profits will be in the next year. By comparison, Novo Nordisk trades at a multiple of 39. With a much higher premium, there's more pressure for Eli Lilly to deliver on not just its weight loss and diabetes treatments but on its other drugs as well.
Will Novo Nordisk become the more valuable healthcare stock?
Over the past month, shares of Eli Lilly have fallen by about 3% while Novo Nordisk stock has risen by close to 7%. The gap is shrinking between these two companies and there's a possibility it narrows even more narrow later this year, depending on how these businesses perform.
I don't, however, expect Novo Nordisk to become the more valuable company. Eli Lilly is simply too strong, and with Zepbound in its very early innings of generating revenue and the approval of donanemab still a strong possibility, the recent pullback in price may only prove to be temporary.
Overall, these are two solid healthcare stocks and whichever you decide to invest in may ultimately depend on whether you prefer to focus on the broader and pricier business (Eli Lilly) or a slightly cheaper company whose priorities center around diabetes and weight loss (Novo Nordisk). But with stellar results and exciting futures ahead, both of these stocks can be great buys.
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re: CRDF
I don't see how any analyst writing about CRDF can fail to mention Pfizer's involvement with the company. Pfizer has taken a tiny equity stake in CRDF and Adam Schayowitz (from Pfizer) has been added to the BOD. The trials changed direction after Schayowitz's appointment and Pfizer is now running the lead trial in CRC.
Bladerunner
PIper Sandler raises price target on CRDF from $5 to $7. Stock up 25%.
Bladerunner
CRDF: Change of opinion by "Seeking Alpha" analyst
Cardiff Oncology: Why The Bulls Are Winning Right Now (Rating Upgrade)
Mar. 08, 2024 7:37 PM ET Cardiff Oncology, Inc. (CRDF) Stock 8 Comments2 Likes
Galzus Research
Summary
Cardiff Oncology is focused on developing a drug for colorectal cancer and pancreatic cancer, with promising early activity shown in colorectal cancer patients.
The company is now focused on moving their drug to the first-line setting and has started a clinical trial to evaluate its efficacy.
Cardiff Oncology has a strong financial position with enough funds to operate through Q3 2025, but the success of their drug is heavily dependent on the outcomes of a single trial.
Topline Summary and UpdateCardiff Oncology (NASDAQ: CRDF) is a cancer-focused biotech working on developing a drug that exploits a novel target, particularly in colorectal cancer. In my past articles, I have been lukewarm to slightly pessimistic about their findings presented to date and their overall outlook. But recent news has sent them on a meteoric rise, and the ensuing roller coaster has readers asking me directly for input on this company. So let's examine what happened to lead to this strong rise in value, as well as where I think they might be headed next.
Pipeline UpdatesOnvansertib
Today, the PLK1 inhibitor onvansertib remains the one and only drug in development by CRDF, meaning its entire future rests on the success or failure of this agent. It is being studied mainly in a few forms of gastrointestinal cancer, namely colorectal cancer and pancreatic cancer, both representing critical unmet needs in oncology.
Most of the focus I've given in my previous writings has been for the colorectal cancer program, which has demonstrated some encouraging (though early) activity in the setting of KRAS -mutant, metastatic disease. Updated findings using add-on onvansertib with FOLFIRI-bevacizumab in the second-line setting have since been published in Clinical Cancer Research, showing a 44% response rate among 18 patients, with reasonable toxicity.
Now, the company's focus is on moving onvansertib to the first-line setting, hurdling over the typical path we have taken in targeted therapy development of starting with more "dire" clinical settings, establishing efficacy, and then moving them up. The phase 2 CRDF-004 study is seeking to randomize 90 patients with newly diagnosed, metastatic, KRAS or NRAS mutated CRC to receive first-line doublet chemotherapy plus bevacizumab, with or without one of 2 doses of onvansertib. The primary endpoint is objective response rate. CRDF announced that the first patient was dosed in this study on leap day. Initial top-line findings are anticipated later this year.
The phase 2 ONSEMBLE second-line study has been discontinued to focus on the frontline study, but CRDF provided an update in their most recent guidance that they interpret as evidence that patients who had no prior bevacizumab seemed to have better response rates, as high as 50%. It is worth keeping in mind that the patient numbers are small here, and in the standard of care, most patients with KRAS mutated mCRC are going to receive bevacizumab as part of their care, so it's difficult to interpret these findings with any real de
We've also gotten glimpses of clinical development for onvansertib in non-CRC settings. Most notably, a report of activity back in September suggests preliminary benefit from onvansertib in metastatic pancreatic cancer and extensive-stage small cell lung cancer. In particular, 4 of 21 patients with pancreatic cancer treated with add-on onvansertib (plus nal-IRI and 5-FU) yielding a 19% objective response rate, which tracks favorably with the findings from NAPOLI-1. A single response was observed with onvansertib monotherapy in the 7 patients with SCLC.
Financial OverviewAs of their most recent earnings report, CRDF held $77.4 million in total current assets, including $21.7 million in cash and equivalents, and another $53.2 million in short-term investments. Their reported annual loss was $45.4 million, with a recognized net loss of $41.4 million after interest income and other expenses.
Given these expenses, CRDF has upwards of 2 years of cash and assets on hand to fund activities, with a serious going concern emerging about a year from now at the current burn rate, by my estimation. This is consistent with guidance from the company saying they have funds to operate through Q3 2025.
Strengths and RisksStrength - CRDF's fiscal management focuses on high-priority studies
For a company in the middle of developing a drug, CRDF has a rather low cash burn rate. This could help give them time to get a data readout that propels them to the levels that we've seen recently with the likes of Janux Therapeutics, where relatively small numbers rev up a huge cash raise. Such penny-pinching stewardship is admirable, although there is a catch
Risk - Careful prioritization places most eggs in one basket
CRDF is now resting almost everything on the CRDF-004 study, and this trial is taking a risky step moving things into the frontline setting. Despite it being at the FDA's recommendation (according to the company), the observation in their 2 early studies that bevacizumab-naive patients seemed to derive the most benefit from onvansertib is shaky to me. These are small patient numbers, and I don't feel this is a hypothesis that's been carried through rigorously enough at this point.
That doesn't mean I think they're wrong, and I don't think it's a wantonly reckless step to go first line. If onvansertib really does work best in bev-naive patients, then this should end up being the exact play they need to make. But it's based on an idea that comes from pretty small patient numbers, and CRDF-004 may not generate convincing-enough findings to really show that onvansertib is moving the needle. All investors should be aware of that risk before jumping in.
Bottom-Line Summary: Why the Rating Change?As of late, developmental biotech companies are undergoing a surge of interest, with multiple companies showing promising phase 1 data sending them into market caps of billions. I do not think this is necessarily justified, but it speaks to the power of encouraging early data. CRDF, even after its recent gains, has the opportunity to surge even higher if their anticipated mid-2024 data readout in CRC shows support for their idea that onvansertib has more benefit in patients with no exposure to bevacizumab (which would be true of all first-line patients).
Tackling KRAS would be a huge coup, since there are currently no approved therapies that are specifically beneficial for patients in the frontline setting of mCRC with KRAS mutations. It's only used right now to help determine what therapies patients should not receive.
All said, I'm upgrading my rating to a "strong buy," which means that I think you should take a serious look at their portfolio and consider entering into a limited position. I would warn heavily against overextending, though, since so much of the company's value is now going to be tied to the outcomes of a single trial, and a lot can go wrong there. But it is clear now that the ceiling is too high to ignore for this company.
Bladerunner
Mind Medicine Inc (MNMD) - >>> Single dose of LSD provides immediate and lasting relief from anxiety, study says
CNN
by Sandee LaMotte, CNN
March 7, 2024
https://www.yahoo.com/lifestyle/single-dose-lsd-provides-immediate-120037213.html
A clinical trial’s encouraging results won US Food and Drug Administration breakthrough therapy status for an LSD formulation to treat generalized anxiety disorder, Mind Medicine Inc. announced Thursday. The biopharmaceutical company is developing the drug.
“A breakthrough designation is a recognition that a drug has demonstrated evidence of clinical efficacy in meeting an unmet medical need with morbidity and mortality associated with it,” said Dr. Daniel Karlin, assistant professor of psychiatry at Tufts University School of Medicine in Boston and chief medical officer for MindMed.
MindMed’s MM120 will still go through the standard FDA approval process, including phase III trials.
The designation, however, “is an offer from the agency to engage more closely in drug development,” Karlin said. “It affects timelines of response and our ability to get more interactions with the agency so that we can be sure that we’re in lockstep agreement as we move forward.”
Two other companies have also received FDA breakthrough therapy status: psilocybin for treatment-resistant depression and to MDMA, (3,4-Methyl?enedioxy?methamphetamine) commonly known as ecstasy or molly, for post-traumatic stress disorder or PTSD.
New results on efficacy at 12 weeks
A single dose of MM120 (lysergide d-tartrate) led to a 48% rate of remission from generalized anxiety disorder at 12 weeks following the drug’s administration, according to MindMed.
The MM120 drug also significantly improved clinical signs of generalized anxiety disorder for 65% of patients within three months, according to results of the phase 2b trial designed to test dosage levels, the company said.
Anxiety is the most common mental disorder in the United States, affecting over 40 million people age 18 and older each year, according to the Anxiety and Depression Association of America. Generalized anxiety order is characterized by excessive, ongoing thoughts that are difficult to control and interfere with day-to-day activities.
“The clinical improvement for many patients was more than double what we see with today’s standard of care,” Karlin said. “This occurred at all levels of anxiety, from moderate all the way up to severe.”
Standard of care for generalized anxiety disorder is a combination of cognitive behavioral therapy and medications such as selective serotonin reuptake inhibitors, or SSRIs, and buspirone — both of which work on levels of serotonin in the brain — as well as sedatives called benzodiazepines.
All of these medications need time to work and may require experimentation with various doses, adding time and expense to a patient’s treatment, Karlin said.
Determining proper dosage
The multicenter, randomized, double-blinded trial tested doses of 25, 50, 100 and 200 micrograms compared with a placebo.
“We’re very confident based on the results that 100 micrograms is the right dose to bring into our phase three studies, as we didn’t see any more improvement with 200 micrograms but did see additional adverse effects,” Karlin said.
Professor David Nutt, director of the Neuropsychopharmacology Unit at Imperial College London’s division of brain sciences, who researches psychedelics, said in an email that the study results “are very exciting data in what can be a difficult to treat population (anxiety).”
“They expand the likely utility of psychedelic treatment beyond depression,” said Nutt, who was not involved in the research. “And again, as with the depression trials, a single dose produces enduring effects, probable due to its breaking down persistent negative thought processes.”
While it was not the study’s primary purpose, results did show that MM120 also improved signs of depression, Karlin said. “We saw rapid and robust improvement on depression symptoms in people — depression and anxiety have overlapping disease definitions.”
No use of psychotherapy
Most research with MDMA and psilocybin has relied on the use of trained therapists who meet and establish a rapport with participants before the drug is administered. Those therapists are then on hand during the “trip” to help each person assimilate the experience, thus helping assure the lasting impact of any psychological insights.
The MM120 study, however, was accomplished without the use of psychotherapy during the session. Instead, monitors sat in the room to assure safety, but spent their time “mostly reading books,” Karlin said.
“While prior research has documented the benefits of combining LSD with psychotherapy to alleviate anxiety associated with life-threatening conditions, this groundbreaking study is the first to show that a single dose of LSD … can effectively treat generalized anxiety without the adjunct of psychotherapy,” said psychiatrist Dr. Gabriella Gobbi, a professor and scientist at McGill University Health Centre in Montreal and Canada Research Chair in Therapeutics for Mental Health. She was not involved in the clinical trial.
Compared with experiences with forms of LSD purchased illegally on the street, the study’s grade of MM120 did not appear to induce “bad trips,” Karlin said.
“LSD is difficult to manufacture with high purity and tends to degrade quickly in the presence of light and water,” Karlin said. “We’re manufacturing it to pharmaceutical industry standards, a highly pure version that is also shelf stable. So that’s a critical difference.”
Most adverse effects in the study were rated as mild to moderate by participants, occurring mostly on the day of the study, Karlin said. Those included euphoric feelings, illusions and hallucinations, anxiety, abnormal thinking, headaches, dizziness, nausea, excessive sweating, vomiting, numbness or tingling of the skin, and pupil dilation.
A long history of LSD research
When the MM120 clinical trial began in August 2022, it marked the first time LSD had been studied in a medical setting in over 40 years, Karlin said.
During the 1940s and early 1950s, tens of thousands of patients took LSD and other psychotropics to study their effects on cancer anxiety, alcoholism, opioid use disorder, depression, and post-traumatic stress disorder or PTSD. Researchers began to see psychedelics as possible “new tools for shortening psychotherapy.”
But when Harvard University psychologists Timothy Leary and Richard Alpert were fired from the Harvard Psilocybin Project in 1963 after the university discovered they had been giving LSD to their students, the use of psychedelics for research began to lose its luster.
Leary began to speak out publicly, encouraging young people to take LSD recreationally. He quickly became the face of the drug counterculture movement with his signature message, “Turn on, tune in, drop out.”
No longer administered solely in the relative safety of a lab or psychiatrist’s office, LSD began to feature in horror stories of bad “acid” trips at colleges and concerts — headlines that appeared alongside images of anti-Vietnam protests and Woodstock attendees.
In 1968, the United States outlawed LSD and research projects were shut down or forced underground. Then came the 1970 Controlled Substances Act, signed by President Richard Nixon. It classified all hallucinogenics, including psilocybin, as Schedule I drugs — substances with “no currently accepted medical use” and a high probability of abuse.
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Blade, Nice going with IOVA :o) Also, a nice move with CRDF, and JSPR is having a nice bounce. I'll check out the other picks, Thanks :o)
The only bio stock I've been following lately has been Acurx (ACXP). They have a new antibiotic approach for C. Dif infections, with a small Phase 2b completed, but very limited durability data available. Phase 3 is planned for later this year, but looks like the Phase 2b data may not be sufficient to get a decent partnership deal, which will mean dilution. So a typical biotech, with lots of promise but plenty of risk :o)
'Amtagvi / Lifileucel' ---> You have to wonder how they come up with these names lol. Probably an Ai program, but they are tongue twisters ..
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IOVA announces lifting of clinical hold in NSCLC
Iovance Biotherapeutics Announces FDA has Lifted Clinical Hold on the IOV-LUN-202 Registrational Trial in Non-Small Cell Lung Cancer
Iovance Biotherapeutics, Inc.
Mon, March 4, 2024 at 3:30 AM PST
In this article:
IOVA
-0.60%
Watchlist
Watchlist
Recommendation Rating
Buy
Iovance Biotherapeutics, Inc.
Iovance Biotherapeutics, Inc.
SAN CARLOS, Calif., March 04, 2024 (GLOBE NEWSWIRE) -- Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, today announced that the U.S. Food and Drug Administration (FDA) lifted a partial clinical hold placed on the registrational IOV-LUN-202 trial investigating LN-145 TIL cell therapy in non-small cell lung cancer (NSCLC). In collaboration with the FDA and an independent data monitoring committee, Iovance developed additional safety measures and monitoring. Upon reviewing this proposal, the FDA has cleared Iovance to resume patient enrollment in IOV-LUN-202.
The IOV-LUN-202 trial is investigating LN-145 in patients with advanced (unresectable or metastatic) NSCLC without EGFR, ROS or ALK genomic mutations who were previously treated with chemotherapy and anti-PD-1 therapy and at least one line of an approved targeted therapy if indicated by other actionable tumor mutations. Iovance expects to complete enrollment of approximately 120 patients in the IOV-LUN-202 registrational cohorts in 2025.
Preliminary data from the IOV-LUN-202 trial support the potential benefit of one-time TIL therapy, including the opportunity for more durable responses than available second line chemotherapies. Initial preliminary data were reported in July of 2023. An updated analysis in November of 2023 showed additional ongoing responses and duration of response greater than six months for 71% of the confirmed responders in the trial.
For more information about the IOV-LUN-202 trial please visit www.lungcelltherapy.com.
About Iovance Biotherapeutics, Inc.
Iovance Biotherapeutics, Inc. aims to be the global leader in innovating, developing, and delivering tumor infiltrating lymphocyte (TIL) therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. Iovance’s Amtagvi™ is the first FDA-approved T cell therapy for a solid tumor indication. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, that may extend and improve life for patients with cancer. For more information, please visit www.iovance.com.
Amtagvi™ and its accompanying design marks, Proleukin®, Iovance®, and IovanceCares™ are trademarks and registered trademarks of Iovance Biotherapeutics, Inc. or its subsidiaries. All other trademarks and registered trademarks are the property of their respective owners.
Bladerunner
gfp,
I'm holding all my IOVA. As you suggest, Lifileucel may (probably?) has applications in other cancers. It certainly looks like a buyout candidate, although that's not a reason to hold the stock.
Bladerunner
Hey gfp,
I don't follow MEIP any longer and haven't for a long time.
My largest position in terms of dollars is IOVA. Lififeucel recently approved and he stock has risen considerable.
In terms of shares, CRDF is my largest position. I was upgraded at Piper Sandler last week with the price target being raised from $5 to $7.
Other large positions of mine include IMMP, BCAB, JSPR, and GRTS.
Bladerunner
>>> Why Iovance Biotherapeutics Stock Is Skyrocketing Today
by Keith Speights
Motley Fool
February 20, 2024
https://finance.yahoo.com/news/why-iovance-biotherapeutics-stock-skyrocketing-160233478.html
Shares of Iovance Biotherapeutics (NASDAQ: IOVA) had skyrocketed by 33.8% as of 10:39 a.m. ET Tuesday. The huge gain came after the company announced on Friday that the Food and Drug Administration (FDA) had granted accelerated approval for Amtagvi (lefileucel) as a treatment for advanced melanoma.
Because of the Presidents' Day holiday, the stock market was closed on Monday. Investors had to wait until Tuesday to push Iovance's share price higher.
Iovance also announced on Tuesday morning the pricing of an underwritten offering to issue just over 23 million new shares for $9.15 per share. That stock sale will generate gross proceeds of around $211 million. Part of the money will be used to support the commercial launch of Amtagvi.
How big is the FDA approval for Iovance?
It's hard to overstate just how important the FDA's approval of Amtagvi is for Iovance. The company is no longer a clinical-stage biotech -- it now has a marketable product. And not just any product: Amtagvi is the first (and so far, only) individualized T-cell therapy to win a thumbs-up from the FDA to treat a solid tumor.
Iovance is also evaluating Amtagvi in late-stage clinical studies targeting cervical cancer and non-small cell lung cancer. Analytics company GlobalData projects that Amtagvi will generate annual global sales of nearly $900 million by 2029.
Is Iovance Biotherapeutics stock a good pick to buy now?
With a market cap of nearly $3.2 billion, much of the anticipated growth for Iovance is already priced into the stock. However, the company could still have more catalysts on the way, including potential regulatory approvals for Amtagvi in other countries. I think Iovance stock remains a good pick to buy for aggressive investors.
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Blade, Just curious about your strategy with Iovance? It sounds like a platform technology, and could have much broader applications in other solid tumors types. I see they announced a financing yesterday, priced at 9.15, but the stock blew right past that level to 15, and is now 16 in after hours.
Anyway, just curious to get your take on Iovance. Thanks for any insights :o)
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Iovance - >>> FDA approves groundbreaking treatment for advanced melanoma
NBC News
by Erika Edwards and Anne Thompson and Marina Kopf
2-16-24
https://www.msn.com/en-us/health/other/fda-approves-groundbreaking-treatment-for-advanced-melanoma/ar-BB1ioIYQ?OCID=ansmsnnews11
The Food and Drug Administration on Friday approved a new cancer therapy that could one day transform the way a majority of aggressive and advanced tumors are treated.
The treatment, called Amtagvi, from Iovance Biotherapeutics, is for metastatic melanoma patients who have already tried and failed other drugs. It’s known as TIL therapy and involves boosting the number of immune cells inside tumors, harnessing their power to fight the cancer.
It’s the first time a cellular therapy has been approved to treat solid tumors. The drug was given a fast-track approval based on the results of a phase 2 clinical trial. The company is conducting a larger phase 3 trial to confirm the treatment’s benefits.
“This is going to be huge,” said Dr. Elizabeth Buchbinder, a senior physician at Dana-Farber Cancer Institute in Boston. Melanoma is “not one of those cancers where there’s like 20 different” possible treatments, she said. “You start running out of options fast.”
Friday’s approval is only for melanoma, the deadliest form of skin cancer, but experts say it holds promise for treating other solid tumors, which account for 90% of all cancers.
“It is our hope that future iterations of TIL therapy will be important for lung cancer, colon cancer, head and neck cancer, bladder cancer and many other cancer types,” said Dr. Patrick Hwu, chief executive of the Moffitt Cancer Center in Tampa, Florida. Moffitt has been involved with Iovance’s clinical trials of TIL therapy.
TIL stands for tumor-infiltrating lymphocytes, which are immune cells that exist within tumors. But there are nowhere nearly enough of those cells to effectively fight off cancer cells. TIL therapy involves, in part, extracting some of those immune cells from the patient’s tumor and replicating them billions of times in a lab, then reinfusing them back into the patient.
It’s similar to CAR-T cell therapy, where healthy cells are taken out of a person’s body and then modified in a lab to fight cancers. That’s usually used for hard-to-treat blood cancers such as leukemia and lymphoma. With TIL therapy, the cells used are already programmed to recognize cancer — no lab modifications needed — they just need a boost in numbers to fight it.
Like CAR-T, TIL therapy is a one-time treatment, though the entire process can take up to eight weeks. The TIL cells are first harvested from the tumor through a minimally invasive procedure and then grown and multiplied in the lab, a process that takes 22 days, according to Iovance.
While that’s happening, patients are given chemotherapy to clear out their immune cells to make room for the billions of new melanoma-fighting TIL cells. Once the TIL cells are reinfused back into the body, patients get a drug called interleukin-2 to further stimulate those cells.
Hwu said that most side effects in patients undergoing TIL therapy are not from the reinfusion of cells, but from the chemotherapy and the interleukin-2. These can include nausea and extreme fatigue, and patients are also vulnerable to other illnesses because the body is depleted of disease-fighting white blood cells.
Putting billions of cells back into the body is not entirely risk-free, however, said Dr. William Dahut, chief scientific officer of the American Cancer Society. It’s possible that the body’s immune system could overreact in what’s known as a cytokine storm, which can cause flu-like symptoms, low blood pressure and organ damage. “There are risks for immune-related side effects, which could be serious,” he said.
Common side effects associated with Amtagvi can include abnormally fast heart rate, fluid buildup, rash, hair loss and feeling short of breath, the FDA said.
Those side effects can be managed, said Dr. Steven Rosenberg, chief of the surgery branch at the National Cancer Institute. “They’re a small price to pay for a growing cancer that would otherwise be be lethal.”
Overall, Dahut said the approval of TIL therapy is “meaningful.”
“What’s nice about this is that patients will receive a wide variety of tumor fighting lymphocytes that will be able to have the capacity to overcome resistance and actually be a living therapy over time, too, to target additional cancer cells should they develop,” Dahut said.
In addition to melanoma, Dahut said that TIL therapy is most likely to be useful in cancers that respond to drugs that “take the brakes off the immune system,” called checkpoint inhibitors.
“Those would be things like non-small cell lung cancer, kidney cancer, maybe bladder cancer, that we know are responsive to immune-based therapies to begin with,” he said. “Many of those patients relapse, so another immune-based therapy that works in a different way, seems to me, the most likely way for this to be effective.”
Much more research is needed, and it may be years before TIL therapy is approved for other types of cancer.
One of Iovance’s clinical trials investigating TIL therapy for non-small cell lung cancer was forced to pause when a participant died. While the death is under investigation, the company said it may have been the result of either chemotherapy or interleukin 2 — therapies meant to knock down each patients’ immune system before they can get the reinfusion of their TIL cells.
The therapy is not expected to work for every metastatic melanoma patient. Clinical trial data that Iovance submitted to the FDA showed that tumors shrank in about a third of patients who received TIL therapy.
Of those patients, about half saw their tumors shrink for at least one year, Dr. Friedrich Graf Finckenstein, chief medical officer of Iovance Biotherapeutics. “Some of these patients even had their tumor completely disappear,” he said.
Another study, conducted in the Netherlands, did a head-to-head analysis of TIL therapy and another form of immunotherapy, called ipilimumab. Twenty percent of the patients who received TIL had complete remissions, compared with 7% of patients who got ipilimumab. Iovance was not involved with the Dutch trial.
The goal of the therapy, Hwu said, “is to get rid of the cancer and have it stay away. These immune cells stay in the body and live in the body for decades.”
The technology has been in development and studied for nearly 40 years. It was Rosenberg who pioneered TIL therapy — first describing how it could shrink melanoma tumors in the New England Journal of Medicine in 1988.
“I’ve been waiting for a very long time to see this given to patients, because I know that it can cure some patients that have metastatic melanoma that cannot be affected by any other treatment,” Rosenberg said.
It’s worked so far for Dan Bennett, 59, of Clermont, Florida. Bennett was diagnosed with melanoma in 2011 after his daughter noticed a suspicious mole on his neck that had changed color.
Despite surgery, chemotherapy and radiation, his cancer kept returning. In 2014, his doctors at Moffitt recommended he try TIL therapy.
“At first, we were pretty leery about it because it was unproven,” Bennett said. Ten years later, Bennett is convinced the TIL therapy is the reason he has survived so long with stage 4 melanoma, which usually has a five-year survival rate of 22.5%.
“I would recommend any experimental drug if it’s your last opportunity,” he said. “You owe it to yourself and your family to do whatever you can to stay alive and to be a productive member of society.”
Buchbinder, the Dana-Faber doctor, was not involved with Iovance’s TIL therapy trial for melanoma, but she is scheduled to begin similar trials with other drugmakers.
“We literally have patients right now waiting for approval because they are hoping they’ll be able to go on it,” Buchbinder said. “It is definitely a practice-changing therapy.”
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>>> Acurx Announces Positive Extended Clinical Cure Data for Ibezapolstat from Phase 2b Clinical Trial in CDI Patients
PR Newswire
Jan 29, 2024
https://finance.yahoo.com/news/acurx-announces-positive-extended-clinical-120000145.html
In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection
Further analyses will be forthcoming as data become available regarding effects on bile acid metabolism and pharmacokinetic data
Preparation is underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Jan. 29, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation.
According to Dr. Garey: "CDI has long-term consequences including poor quality of life for the patient. It's exciting to see that the ibezapolstat Phase 2b study followed patients for an extended time period to assure that the ibezapolstat cure and anti-recurrence effects are long-lasting and durable. This adds to the exciting microbiome data showing replenishment of healthy microbiota that we have seen in our prior studies."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This Extended Clinical Cure data showing that no ibezapolstat-treated patient who achieved Clinical Cure and consented to three months of post-treatment observation experienced a recurrence of CDI during this period further strengthens the ibezapolstat lineage of clinical success building on our previously reported Phase 2 results of 96% Clinical Cure and 100% Sustained Clinical Cure along with favorable preservation of the microbiome and no safety signals." He further stated: "We look forward to advancing to Phase 3 clinical trials and are optimistic about achieving non-inferiority versus vancomycin which is the regulatory clinical development hurdle for marketing registration".
David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate continued favorable differentiation between the two therapeutic options in 2024. We expect to leverage this success in a $1 billion plus US CDI global market as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also anticipates its price point for ibezapolstat, if approved, could meet or beat other antibiotics recommended for use in treating patients with CDI, thereby providing the whole package of clinical comparability with microbiome health, safety and cost for patients with this life-threatening disease."
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.
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. The Company previously reported that 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).
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 and its aftermath. The Company had 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 was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
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.
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 C. 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 late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial 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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>>> Novo Nordisk A/S (NVO), a healthcare company, engages in the research, development, manufacture, and marketing of pharmaceutical products worldwide. It operates in two segments, Diabetes and Obesity care, and Rare Disease.
The Diabetes and Obesity care segment provides products in the areas of insulins, GLP-1 and related delivery systems, oral antidiabetic products, obesity, glucagon, needles, and other chronic diseases.
The Rare Disease segment offers products in the areas of haemophilia, blood disorders, endocrine disorders, growth disorders, and hormone replacement therapy.
The company has a collaboration agreement with Gilead Sciences, Inc.; and research collaboration with Novo Nordisk to discover cell-specific carriers of nucleic acid therapeutics. The company was founded in 1923 and is headquartered in Bagsvaerd, Denmark.
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https://finance.yahoo.com/quote/NVO/profile?p=NVO
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>>> FDA says cancer treatment CAR-T therapy may increase risk of cancer
NBC News
by Berkeley Lovelace Jr.
January 24, 2024
https://www.yahoo.com/news/fda-says-cancer-treatment-car-020945813.html
The Food and Drug Administration this week told several drugmakers to add a boxed warning — the agency’s strongest safety label — to the prescribing information for a type of cancer treatment called CAR-T therapy, saying the treatment itself may increase a person’s risk of cancer.
Carly Kempler, a spokesperson for the FDA, said that, despite the warning, "the overall benefits of these products continue to outweigh their potential risks."
The agency’s decision to update the labels was based on reports of rare blood cancers in patients who had previously gotten CAR-T therapy, Kempler said. As of Monday, the agency had received 25 reports of the blood cancers in CAR-T patients, she said.
Bruce Levine, a professor in cancer gene therapy at the University of Pennsylvania, said that in addition to the reports submitted to the FDA, two abstracts published late last year in the journal Blood also cited a potential cancer risk associated with CAR-T therapy, which likely “forced the FDA’s hand.”
CAR-T — or chimeric antigen receptor T cell — therapy uses a patient’s own immune cells to treat certain blood cancers, such as leukemia, multiple myeloma and lymphoma. It involves harvesting the immune cells — in this case, T cells — then genetically altering them in a lab to make them target cancer cells, and finally reinfusing them back into the patient.
It’s proven to be highly effective in hard-to-treat cases, experts said. In 2022, doctors who had treated two leukemia patients with CAR-T a decade ago said it was fair to say the therapy had cured the patients of the disease.
“This has been a game changer when we think about treating lymphoma and other diseases,” said Dr. Matthew Frigault, the clinical director of the Massachusetts General Hospital Cellular Immunotherapy Program in Boston.
The first CAR-T therapy, Novartis’ drug Kymriah, received FDA approval in 2017. Since then, another five have been approved.
The makers of the drugs — Bristol Myers Squibb, for Abecma and Breyanzi; Gilead Sciences' Kite Pharma, for Yescarta and Tecartus; Johnson & Johnson's Carvykti; and Novartis, for Kymriah — received letters from the FDA, stating that they must submit proposed label changes in the next 30 days to note that, in rare cases, CAR-T therapy can increase the risk of rare blood cancers.
If the drugmakers disagree, they can instead submit a rebuttal explaining why a change isn’t needed.
In a statement to NBC News, a spokesperson for Novartis said the company has not found “sufficient evidence” to support a link between cancer and its treatment, which has been used in more than 10,000 patients. However, the spokesperson said, the company will work with the FDA to update its label “appropriately.”
Spokespersons for Johnson & Johnson and Gilead Sciences also said the drugmakers would work with the agency to update their labels.
A spokesperson for Bristol Myers Squibb said the company is evaluating “next steps” following the FDA’s notice, although it has not seen any cancer cases associated with its treatment.
“Patient safety is our top priority,” the spokesperson said.
How might CAR-T therapy cause cancer?
Still, there’s the question of how CAR-T could cause cancer — if it does at all.
“We actually don’t know whether this is causal, meaning, we don’t know for a fact that the CAR-T cells in the tumor have led to this,” said Frigault, of Mass General.
CAR-T treatments are still relatively new: Frigault noted that the FDA has required that the makers of the products conduct 15-year follow-up studies to assess the potential risk of secondary cancers following treatment. (Secondary cancers are cancers that can arise from treatment.)
The FDA “is not saying that every single one of the cases they’ve reported has clearly shown CAR-T has led to this,” he said, “but more that there may be an association.”
“This is what the FDA does. They look for a signal,” he added.
If CAR-T does cause cancer, the risk is likely very small, said Dr. Hemant Murthy, a hematology-oncology physician at the Mayo Clinic in Jacksonville, Florida.
More than 27,000 doses of CAR-T therapy have been administered in the U.S., according to the FDA.
“I don’t really see this affecting too much of practice,” Murthy said.
Dr. Saad Usmani, a myeloma physician and cell therapist at Memorial Sloan Kettering, said the label change should support physicians’ current practice of discussing with patients the risk of developing secondary cancers following cancer treatment.
Usmani noted that other cancer treatments, such as radiation and chemotherapy, also carry a risk of secondary cancers.
“The change is expected given the recent reports, albeit very low incidence in such cases,” he said.
Dr. Marcela Maus, an associate professor of medicine at Harvard Medical School and director of the Cellular Immunotherapy Program at Massachusetts General Hospital, said physicians might be more cautious, but it most likely won’t change much in their practice.
“We need to manage the cancer that they have now, so I don’t imagine it being massively different,” she said.
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>>> Acurx Pharmaceuticals to Present at the Microcap Conference, January 31, 2024 - February 1, 2024
PR Newswire
January 23, 2024
https://finance.yahoo.com/news/acurx-pharmaceuticals-present-microcap-conference-120100998.html
STATEN ISLAND, N.Y., Jan. 23, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. ("Acurx" or the "Company") (NASDAQ: "ACXP"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced that David P. Luci, President & Chief Executive Officer, will be presenting at The Microcap Conference, which will take place January 30, 2024-February 1, 2024 at the Ceasars Atlantic City Hotel & Casino in Atlantic City, New Jersey.
Presentation Details:
Wednesday, January 31st, 2 pm ET and
Thursday, February 1st at 11:40 am ET
Interested parties can register to attend here.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial 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 Positive Comparative Microbiology and Microbiome Data for Ibezapolstat from Phase 2b Clinical Trial in CDI Patients
Yahoo Finance
January 17, 2024
https://finance.yahoo.com/news/acurx-announces-positive-comparative-microbiology-120100113.html
Ibezapolstat outperformed vancomycin showing eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 treated patients (94%), versus vancomycin which had eradication of C. difficile in 10 of 14 treated patients (71%).
Ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent recurrence of CDI
Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days
Preparation underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Jan. 17, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced positive comparative microbiology and microbiome data for ibezapolstat, its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. Data showed that ibezapolstat outperformed vancomycin, a standard of care to treat patients with CDI, with eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 patients (94%) versus vancomycin which had eradication of fecal C. difficile in 10 of 14 patients (71%). In addition, ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent CDI recurrence. Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days. Preparation is underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials.
The Company also announced that a scientific poster will be presented on January 18, 2023 at the Gulf Coast Consortia Antimicrobial Resistance (AMR) Conference in Houston, Texas by Kevin Garey, PharmD, MS, Professor and Chair, University of Houston College of Pharmacy, the Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member. The poster will show comparative data details from the Phase 2b clinical trial entitled: "A Phase 2, Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides difficile Infection."
After the presentation, the poster will be posted on Acurx website: www.acurxpharma.com
According to Dr. Garey: "These results help validate our ongoing scientific investigations into the anti-CDI recurrence effects of ibezapolstat. Our microbiologic findings show that markedly fewer patients treated with ibezapolstat had persistent C. difficile compared to patients treated with vancomycin. He further stated: "Preservation of key health-conferring native gut bacteria, such as Firmicutes, in patients treated with ibezapolstat has now been shown consistently during all clinical studies. These results correlate with prior findings by showing superior preservation of key native gut bacteria compared to vancomycin in CDI patients. Preservation of native gut bacteria during treatment for CDI is believed to be a key component for preventing recurrence of CDI. These findings will need to be further validated in the phase 3 studies but the results to date support the importance of this new class of antibiotics with a novel mechanism of action that does not target native gut bacteria."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new comparative data are very important and timely to enhance our data package for an end of Phase 2 FDA Meeting which is targeted for second quarter this year. He further stated: "Parallel preparations continue on schedule for Phase 3 clinical trials start up later this year, including timely availability of clinical trial supply.
David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate that favorable differentiation between the two therapeutic options will continue to be shown in Q1 2024 including extended clinical cure and additional microbiome comparison data. We expect to leverage this success in a $1 billion plus US CDI global market as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also anticipates its price point for ibezapolstat, if approved, could meet or beat other antibiotics recommended for use in treating patients with CDI, thereby providing the whole package of clinical comparability with microbiome health, safety and cost for patients with this life-threatening disease."
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.
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. 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).
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 and its aftermath. The Company had 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 was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
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.
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 C. 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 late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial 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 - The replay of the Jan 11 JP Morgan presentation is up on Acurx's website (links below). Luci said all the remaining data should be out in Jan, and includes the extended durability (94 day), microbiome comparison data, and microbiology comparison data. So the next 2 weeks should be very interesting :o)
https://d3ua9t66dzwd8a.cloudfront.net/HC24/p_50099_Acurx.mp3
https://ir.acurxpharma.com/
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ATM (At The Market) Program -
https://www.investopedia.com/terms/a/atthemarket.asp#:~:text=An%20at%2Dthe%2Dmarket%20(,(and%20a%20better%20price).
>>> At-the-Market Offering FAQs
What Is an At-the-Market Offering?
An at-the-market offering (ATM) takes place after a company goes public, as a sort of follow-up. In an ATM, a company can offer secondary public shares on any given day, usually depending on the prevailing market price, to raise capital.
An at-the-market (ATM) offering gives the issuing company the ability to raise capital as needed. If the company is not satisfied with the available price of shares on a given day, it can refrain from offering them, saving its new shares for another day (and a better price).
ATM offerings are sometimes referred to as controlled equity distributions because of their ability to sell shares into the secondary trading market at the current prevailing price.
How Does an At-the-Market Offering Affect the Stock Price?
Shareholders often react negatively to secondary offerings because they dilute existing shares and many are introduced below market prices. However, unlike the typical 7% to 10% drop in stock price that follows the announcement of a traditional follow-on equity offering, the average stock price change following the announcement of an ATM is minimal—often, just 1% to 3%.
Where Can I Find At-the Market Offerings?
Issuing companies set up ATM programs to prepare prospectuses and issue shares—a streamlined version of a regular initial public offering. A sales agent—usually an investment bank—then circulates news of the ATM to investors and financial firms, announcing a launch date when shares will be available.
Why Do Companies Do At-the Market Offerings?
An ATM offering program may provide a company with a more attractive and less dilutive capital-raising option. The availability of an ATM program also allows a company to take advantage of a temporarily higher stock price, a good earnings report (typically, the best time to launch an offering is shortly after the filing of the issuer’s Form 10-K or 10-Q), or an upcoming milestone event to raise money.
ATMs also tend to be faster and cheaper than traditional IPOs or other follow-on equity offerings. There is no lock-up period, and the incremental sale of shares has a minimal impact on the prevailing stock price.
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Acurx - CEO interview -
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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% |
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Seattle Genetics Inc | SGEN | 2.16% |
Exelixis Inc | EXEL | 2.06% |
ACADIA Pharmaceuticals Inc | ACAD | 2.04% |
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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% |
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Vertex Pharmaceuticals Inc | VRTX | 3.89% |
ACADIA Pharmaceuticals Inc | ACAD | 3.75% |
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Twist Bioscience Corp | TWST | 5.72% |
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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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