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Is this the presentation you are referring to?
Marnix Bosch
CTO
Northwest Biotherapeutics
Day Two
Wednesday, December 11, 2019
11:40 am | DCVax Technology: Leveraging Activated Dendritic Cells in Clinical Development for GBM
https://glioblastoma-drugdevelopment.com/about/speakers/
someone asked Al Musella for more details on the Patient Advocacy Meeting with Northwest Bio, but he couldn’t provide anything further.
https://forum.virtualtrials.org/forum/main-forum/174-sno-update
Dear Dr. Musella. You attended the Patient Advocacy Meeting that Northwest Bio hosted at the SNO Conference on November 23rd.
And I have some questions regarding your point of view and experience with NWBOs DCVax-L fase 3.
1: Who did you talk to at the NWBO meeting?
2: What was your feeling about the time perspective on SAP, data lock and regarding unblinding?
3: With your broad and nuanced experience with GMB, what does your intuition say about PFS as a success criteria?
Thank you in avance.
Per Nielsen Denmar
And this is Al’s reply:
They wouldn't tell me anything secret. The only data they showed was what Dr Liau presented at prior meetings. Nothing new. I get the feeling that it will be good. The longer they wait the better it looks/
senti, I’m also encouraged to see Northwest Bio so engaged with the patient advocacy groups and appreciate that they seem to understand things from a patient perspective, and I’m sure they have established some personal relationships with these groups after so many years of interactions and meetings. I would note that Al listed DCVax first before all of the other treatments even though there wasn’t even a real “update.” This along with his “and it has been a long time” comment indicates that the advocacy groups are probably more anxious than we investors are, (if that’s possible) and they have been waiting and wanting this trial to finish for years. I will also note that the tweet of the picture of Dr. Bosch also thanked Northwest Bio for hosting the meeting. It has to be so frustrating to be a brain cancer patient advocate with the dire prognosis, debilitating effects, and so few treatment options. I saw a slide at SNO that said only 11% of newly-diagnosed brain tumor patients enroll in clinical trials, and that a major goal of SNO and patient organizations is to improve this. And speaking of SNO, Al also said that there were 43 presentations on Optune!! SMH
Wish I could beartrap, but I didn’t attend the meeting nor do I personally know Al Musella. You may be able to post a question on his forum https://forum.virtualtrials.org or contact him here: http://www.virtualtrials.org/feedback.cfm
FWIW: The way I read that, he meant that Northwest knows when the results will be presented. He said that he pressed them on “soon” so that is what they said they knew but couldn’t tell him.
Doktorno, thank you for the laugh. I realize now that I should have been more clear in the post for those readers who are not aware who Al Musella is, and that I was simply reposting a post that he made on his forum. It was he, and not I, who attended the Patient Advocacy Meeting that Northwest Bio hosted at the SNO Conference on November 23rd. Al Musella is a brain cancer patient advocate and President and founder of the Musella Foundation For Brain Tumor Research and Information. http://www.virtualtrials.org/Musella.cfm
And no, I do not tweet. I believe the tweet that you are referring to here: https://twitter.com/HeadfortheCure was from the Head for the Cure Foundation. https://www.headforthecure.org
I think he meant "blinded data"
Al Musella SNO Update
Hi. Just got back from SNO (Society of Neuro-oncology annual meeting). Excellent meeting - overwheling with the amount of information presented. I am going to mention a few of the highlights and welcome others who went to the meeting to post their thoughts.
DCVAX: No updated data was presented but we had a nice meeting with all of the advocacy groups and Northwest bio. They went over the unblinded data that they presented last time and said they will present the final results "soon". I pressed them on that and they said they know but can't tell me. I get the feeling it is going to be pretty good. The longer they wait the better the data will look and it has been a long time.
https://forum.virtualtrials.org/forum/main-forum/174-sno-update
Tocagen: The results from the trial were presented and it did not hit the main endpoint of overall survival in the intent to treat group. A few pre specified subgroups did show impressive results. There was a lot of discussion on reasons why. One possibility is that the trial stopped the oral 5FU part at the first sign of progression. 50% of the patients in the treatment group showed signs of progression at the first scan and were stopped. The average number of cycles of the drug was 2. Looking back, that was probably a terrible idea because with any immunotherapy, there is more swelling on patients who are responding to the therapy best - which appears as progression on scan.. so they stopped the trial early for those most likely to respond.
If you do not include the 1/2 of patients who had to stop at that first scan, the results were much better. However, most likely they have to do another trial to prove it works. They are planning another trial for newly diagnosed gbm, and in the control group they will allow patients to use Optune... so I support the new trial design. All get surgery, radiation and temodar, and are randomized to get tocagen or optune.
If anyone doesn't know what Tocagen is, ask and I will explain
Onc-201: (Diclaimer: The Musella Foundaiton gave a venture philanthropy grant to this company so we will benefit if the drug gets approved). There were a LOT of presentations on this drug and a lot of excitement among the pediatric neuro-oncologists. The data just keeps getting better with something like 80% of patients having a benefit and no serious side effects. There were a few patients who had complete responses, and a few with more than 50% reduction in tumor - which is unheard of for this group of patients (H3K27M mutant diffuse midline glioma and DIPG). Although not a miracle cure, it is a huge step in the right direction. It was noted that in the original trial for glioblastoma, that patients with the H3K27M mutation did much better than those without it, so further development was limited to those with this mutation. About 80% of DIPG patients have it, as do diffuse midline gliomas in mostly young adults). However, a new bit of information came out. Those glioblastomas that did not respond at all, had elevated levels of EGFR. Most diffuse midline gliomas do not overexpress EGFR. This is way too early but brings up the opportunity to test a combination of Onc201 with a EGFR inhibitor, which might work on GBMs with high levels of EGFR! I doubt if this is ever going to get tested until after Onc-201 gets FDA approval but we have to remember to try this at that point!
G47Delta oncolytic virus. This may be a home run. I wrote more about it on another thread. The trials were small but look good. I am working on finding out how to get it. If anyone has luck, let me know!
Neo-adjuvant checkpoint inhibitors: There were a few presentations on this. Since they are approved we can get easy (unless you consider cost
access anywhere. Basically it looks like if you start the checkpoint inhibitors when there is a lot of tumor, it will create a big immune response, but that immune response can't handle a large number of tumor cells. So the best stradegy seems to be start the checkpoint inhibitor when there is tumor, give it a little time to build up, then remove as much tumor as possible, either through surgery or radiation, then continue the checkpoint inhibitor. This is worth considering if you have time before a surgery.
Thank you senti. Your table is so much better than mine. ; ) I thought I read somewhere (maybe Ihub) that it was a 30-day review, so knowing that it is actually a 60-day review, it makes what David Innes said about whether to wait a little longer make more sense. No, we don’t know exactly when it was submitted, but we can probably narrow it down to a couple months. (AUG/SEP) And thank you for pointing out that the manual is outdated (2013) so the part I copied below may not (but probably still does) apply.
Thanks, but it's old news - that was from last February. But being stale doesn't make it any less awesome!
Yes good news, but the major revenues will be a few years away. At the Jefferies Conference in London, Antares provided a little color on the new partnership, and they believe there is huge potential for this product. There are well established P2Y12 blockbuster products like Plavix and Brillinta already on the market for cronic use but Idorsia’s Selatogrel will be used in an emergency, acute setting at the onset of heart attack symptoms. Although terms haven’t been disclosed, Antares will supply a fully assembled product at cost plus margin, and said the royalty will be similar to their arrangements with their other partnerships which are a single to double-digit royalty on end sales. From a royalty standpoint, it could be very meaningful since the product will address a large, global population. They plan to start a phase 2 crossover (bridging) trial, and if successful, will prepare to supply a very large, global, Phase III study in early 2021. If the product is eventually approved, from a marketing standpoint, it will be the largest product for Antares to date.
This article, makes it sound like the bridging studies may have actually started back in September.
Phase 2 data of selatogrel, Idorsia’s highly-selective P2Y12 receptor antagonist, presented at ESC 2019
September 03, 2019
https://www.globenewswire.com/news-release/2019/09/03/1910237/0/en/Phase-2-data-of-selatogrel-Idorsia-s-highly-selective-P2Y12-receptor-antagonist-presented-at-ESC-2019.html
Guy Braunstein, MD and Head of Idorsia Global Clinical Development, added:
“The Phase 2 data demonstrate that subcutaneous administration of selatogrel 16mg in patients with stable CAD and patients with AMI has a rapid onset of action, within 15 minutes, with the effect extending over 4-8 hours. Based on the speed at which selatogrel takes effect, the duration of that effect, and the safety and tolerability profile, self-administration of selatogrel at the very onset of symptoms of a suspected AMI has potential as a highly innovative approach to AMI management.”
In consultation with health authorities, Idorsia is preparing a large, international, multi-center, Phase 3 study to investigate the efficacy and safety of subcutaneous self-administration of selatogrel for the treatment of a suspected AMI in patients with an history of AMI. Participating patients will be trained on when to inject and instructed on how to self-administer treatment. An integrated drug delivery device is being developed through usability and reliability studies to ensure functional efficacy can be demonstrated ahead of the Phase 3 study.
After reading the 10-Q, I was wondering how long the regulatory review process for the SAP could take. Anyone know if this is the correct manual and table? TIA
CDER Manual of Policies & Procedures MAPP
https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/cder-manual-policies-procedures-mapp
OFFICE OF NEW DRUGS
Good Review Practice: Good Review Management Principles and Practices for Effective IND Development and Review
https://www.fda.gov/media/85790/download
Presently, CDER does not have the resources to meet all listed timelines, and must balance this work with other responsibilities, including NDA/BLA review and oversight of postmarketing safety. Meeting all the dates specified in Tables 6 and 7 cannot be accomplished at present. However, CDER has selected several high-priority submissions from these tables and will work toward implementing the goal date over the next several years for these submission types. The high-priority submissions include new phase 2 and phase 3 adaptive trial designs, new phase 3 protocols, and postmarketing requirement protocols (for required postmarketing studies and trials that concern complex designs or statistical assessments).
Table 6. IND Drug Development Submissions (Corresponds to Submission/Amendment Category 3) (Page 36 of 42)
Description / / Recommended Timeline / / Type of Evaluation / / Communication With Sponsor
Statistical analysis plan / / Up to 60 days / / Written review / / As needed
Well there is another way. Have you heard of Contingent Value Rights (CVR’s)? It’s basically an option whose payment is contingent on a future event, and they are sometimes used in mergers and acquisitions. This way some of the risk associated with the deal is placed on the shareholders of the acquired company. They are registered and tradable securities but are pretty illiquid, since their value is very speculative.
One of the most notorious cases of a CVR being used was when Allergan (AGN) bought Tobira (TBRA) a few years ago for their NASH drug (Cenicriviroc) for an upfront cash payment of $28 per share and $50 per share in CVRs. The CVR was based on the successful completion of certain development, regulatory, and commercial milestones; something like $15 per share paid when the first patient was dosed for the phase III trial, $5 paid upon NDA submission, $15 paid upon first commercial sale, $15 paid on $1B in sales, etc.
Actually H2R, that’s 2 days in a row. It reached a new 52-week high yesterday at $4, then hit another new high today at $4.20. I said back in March that I expected ATRS to hit many new 52-week highs, but I was beginning to wonder how long it would take. With the accumulation since the 3rd quarter earnings announcement, it has been difficult to keep the price down. Turning the profitability corner was a very important milestone, but it looks like the large volume was waiting to see if Tlando received approval. Breaking the $4 barrier was definitely nice to see!
Regarding this “manufacturing readiness, which they will need to demonstrate at a pre-BLA stage. “
What do you make of this nugget from the 10-Q?
On November 8, 2019, the Company and Advent entered into an Ancillary Services Agreement with an 8-month Term for the U.K. Facility Development Activities and the Compassionate Use Program Activities. The Ancillary Services Agreement establishes a structure under which Advent will develop Statements of Work (“SOWs”) for each portion of the U.K. Facility Development Activities and Compassionate Use Program Activities, and will deliver those SOWs to the Company for review and approval. After an SOW is approved by the Company, Advent will proceed with or continue the applicable services and will invoice the Company pursuant to the SOW. Since both the U.K. Facility Development and the Compassionate Use Program involve pioneering and uncertainties in most aspects, the invoicing under the Ancillary Services Agreement will be on the basis of costs incurred plus fifteen percent.
It says to me that manufacturing readiness is now at hand with Advent for the UK/EU, since the “Compassionate Use Program” has been supported and manufactured at King’s College London (with the assistance of Fraunhofer Institute in Germany). It seems unusual that the Service Agreement has an 8-month term though. What are they expecting in 8 months?
Yes, it was an excellent quarter! I have to admit that I was disappointed to hear that Teva expects a 2H 2020 launch for generic Forteo. I was hoping for a catalyst this fall, but all in good time I guess. We're getting a good lesson in patience with our investments huh?
Lipocine Receives Complete Response Letter for TLANDO™ from U.S. FDA
https://www.prnewswire.com/news-releases/lipocine-receives-complete-response-letter-for-tlando-from-us-fda-300955195.html
SALT LAKE CITY, Nov. 11, 2019 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a clinical-stage biopharmaceutical company, announced today that it has received a Complete Response Letter ("CRL") from the United States Food and Drug Administration ("FDA") regarding its New Drug Application ("NDA") for TLANDO™, the Company's oral testosterone product candidate for testosterone replacement therapy ("TRT") in adult males for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism. A CRL is a communication from the FDA that informs companies that an application cannot be approved in its present form.
The CRL identified one deficiency stating the efficacy trial did not meet the three secondary endpoints for maximal testosterone concentrations ("Cmax"). The CRL does not identify any specific issues relating to the chemistry, manufacturing and controls ("CMC") of TLANDO.
"We are disappointed by the FDA's decision and intend to request a meeting with the FDA as soon as possible to discuss a potential path forward for the approval of TLANDO," said Dr. Mahesh Patel, Chairman, President and Chief Executive Officer of Lipocine.
I thought there was a decent chance this could happen. Only one deficiency this time. Looks like Antares will have some more time to build market share . . .
Good question. The way you phrased it, do you suspect that Northwest Bio is making false statements in their SEC filings? I doubt it, and I also doubt that a major ramp up is in progress, but I do think that Advent will soon be ready to add to the manufacturing capacity, which should be sufficient for the initial commercialization. I agree that even the Big Pharma companies will often seek initial approval in one market before expanding, so seeking approval in 4 countries simultaneously seems aggressive. But in this case, if one market decides to delay approval for some reason, then there are still multiple other opportunities in the other markets. I have thought that the UK/EU with their Hospital Exemption and PIM designation for DCVAX, seem more eager to approve it than the U.S., and maybe I’m not alone. Or maybe another reason is to create a broader available market to increase the buyout price?
flip, don't stop posting. It makes sense to me. I thought the two Mercks were affiliated, and I was initially excited for the possibilities . . . until senti burst my bubble.
meirluc, it’s not only the manufacturing capacity that will constrain the initial ramp up, but also the number of patients that the qualified medical centers can handle, and the entire personalized-medicine system itself. As we have seen from the commercialization of the first two CAR-T therapies, Kymriah and Yescarta, it takes time to obtain insurance reimbursement, to establish the treatment process and procedures, and to prepare and qualify the multitude of stakeholders at the medical centers that will treat patients. It’s been over two years since these CAR-T treatments were approved, and although neither company has disclosed exactly how many patients they’ve treated so far, (Gilead claims over one thousand) it’s believed to be less than two thousand combined.
In comparison to those treatments, DCVax is less complicated to manufacture, has long-term data for insurance reimbursement, is much safer and doesn’t require the extended hospitalization that the CAR-T treatments do, so in theory, it could be a faster ramp, but initially, (for the first year or two) I think it will be a slower roll-out than many here seem to believe.
No, they’re not, “ready to manufacture 100,000 autologous vaccines a year.” (it will take years to ramp up to that level) From the latest 10-K:
Cognate BioServices' facility is approximately 80,000 square feet, and produces both the Company’s DCVax products and other clients’ products. We believe the current manufacturing facilities have the potential to produce DCVax for at least several thousand patients per year. We are also developing facilities for manufacturing in the U.K. for the European market. It is necessary for us to have manufacturing operations in Europe to meet the logistical requirements for European patients relating to the collection, delivery and processing of the patient’s blood draw containing the immune cells (for which the time window is too limited to reach the US manufacturing facility).
I certainly didn’t forget it (and I do love Baba O’Riley). I’m fascinated by this potentially game-changing technology, and I’ve been looking out for, and looking forward to, whatever the collaboration with Cognate produced. So this is an interesting development, but I’m not sure if it relates to NWBO, (a response to LP’s plea at ASCO?) (will Cognate still develop/utilize it?) or it’s just happenstance that Merck KGaA snapped it up.
And thank you for pointing out that there are two different, unaffiliated companies that use the name MERCK. Merck KGaA, Darmstadt, Germany, which uses the firm name "Merck KGaA, Darmstadt, Germany," in the United States and Canada, and also uses "EMD Serono" in biopharma, "MilliporeSigma" in life science and "EMD Performance Materials" in materials business. The other company, Merck & Co., Inc. holds the rights in the trademark MERCK in the United States and Canada. Merck & Co. is not affiliated with or related to Merck KGaA, Darmstadt, Germany, which owns the MERCK trademark in all other countries of the world.
This may be OT . . . or maybe not?
Merck KGaA acquires acoustic tech to industrialise cell therapy production
11-Oct-2019
Merck KGaA's MilliporeSigma has announced it has acquired Massachusetts-based FloDesign Sonics the developer of a unique acoustic cell processing platform for the industrialisation of cell and gene therapy manufacturing. Financial details of the deal have not been disclosed.
Udit Batra, member of the Merck Executive Board and CEO of Life Science explained that Chimeric antigen receptor T cell therapies (CART-T) employ the body's own immune systems to fight cancer by turning T cells into targeted therapeutics. This revolutionary cancer treatment is challenging and complex, with the process often taking up to a month.
Batra said: "Our acquisition of FloDesign Sonics will industrialise the manufacturing of autologous cell therapy, allowing these types of potentially life-saving treatments to reach more patients, faster."
Merck says it is the first company to make acoustic technology available for cell therapy manufacturing. Acoustic cell processing is a disruptive technology that allows for the manipulation of cells with ultrasonic waves. FloDesign Sonics' acoustic cell processing platform allows enhanced cell washing and concentration for manufacturing cell therapies.
The acquisition is a strategic fit for Merck, strengthening the ability alongside pharmaceutical manufacturers to advance cell-based therapies to patients.
"Merck is the best home for FloDesign Sonics, our acoustic cell processing technology and our employees," said Stanley Kowalski III, co-founder, Chairman and CEO of FloDesign Sonics.
Founded in 2009, the company develops an acoustic cell processing platform for cell and gene therapy applications. FDS just recently (Q1 2019) launched its first commercial product (Ekko) which allows the wash, concentration and formulation within Autologous CAR-T Manufacturing workflow.
Though there has been no relevant commercial revenue yet (2019: €0.8 million), the company has 52 granted patents and >200 applied.
https://www.manufacturingchemist.com/news/article_page/Merck_KGaA_acquires_acoustic_tech_to_industrialise_cell_therapy_production/158988
MilliporeSigma publishes white paper on single-pass tangential flow filtration
17-Sep-2019
https://www.manufacturingchemist.com/news/article_page/MilliporeSigma_publishes_white_paper_on_single-pass_tangential_flow_filtration/158197
Cell Therapy Manufacturing Update: Merck Becomes the First to Introduce Acoustic Technology
By Rohit Kumar October 22, 2019
With its acquisition of FloDesign Sonics earlier this month, Merck/MilliporeSigma has become the first company to introduce acoustic technology in cell therapy manufacturing. The acquisition of FloDesign Sonics is a strategic fit for Merck, strengthening its ability alongside to manufacture cell-based therapies for patients.
What is Acoustic Cell Processing: Acoustic cell processing is a disruptive technology that allows for the manipulation of cells with ultrasonic waves. FloDesign Sonics’ acoustic cell processing platform allows enhanced cell washing and concentration for manufacturing cell therapies. As per an interview with FloDesign Sonics’ CEO, the platform leverages a patented 3D acoustic wave to manipulate cells and particles in suspension. This gentle, non-invasive technology effectively suspends target cells within standing waves in a chamber while material continuously passes through the chamber.
Advantage of Acoustic Cell Processing Over Traditional Approaches: The technology helps the manufacturers to achieve in one process that is traditional achieved separately through filtration, centrifugation, and cell selection. This helps in significantly reducing the time required in training and technology transfer.
What Other Companies are Using This Technology: FloDesign Sonics’ technology is currently being used by Pall Biotech, which offers a portfolio of scalable single-use technologies for continuous bioprocessing. The company’s platform is based on acoustic wave separation that can be used either for clarification of fed-batch cell culture or cell retention in perfusion cell culture.
Last year, FloDesign Sonics signed a technology development collaboration agreement with Cognate BioServices, a leading, CDMO, to advance the accessibility of life-saving therapeutics. The aim of the collaboration was to advance the development of life-saving therapeutics by improving manufacturing efficiencies using FloDesign Sonics’ Acoustic Cell Processing (ACP) platform.
Applikon Biotechnology is another company that is using acoustic technology. According to the company, the Applikon BioSep system is a unique, cell retention device for high-density perfusion processes. The device uses high frequency resonant ultrasonic waves to separate cells instead of a physical mesh or membrane. It, therefore, offers all the benefits of traditional devices but without their inherent problems and limitations. There are a few other companies that claim to be using acoustic technology.
How Does this Impact the Overall Cell Therapy Manufacturing Market? According to a report by Roots Analysis, the novel technologies being developed for cell therapies have the capability to save significant cost in the manufacturing of these therapies.
https://www.rootsanalysis.com/blog/2019/10/22/cell-therapy-manufacturing-update-merck-becomes-the-first-to-introduce-acoustic-technology/
mani, I didn’t say anything about TLD by January 1st. I simply proved that your statement, “nothing gets done between thanksgiving and new year” is completely wrong.
Thanks pgsd. That's what I thought.
Thanks mani. You're a big help.
Linda Liau is listed as a speaker at SNO. Anyone know the topic?
https://www.eventscribe.com/2019/sno/speakers.asp?goToLetter=L&pfp=Speakers
Why would there be communication regarding DCVax-L manufacturing? Cognate has a manufacturing and services agreement from 2014 that is still effective and includes the commercial manufacturing of DCVax-L. There could be negotiations regarding an amendment for commercial scale manufacturing perhaps. If Northwest was going to change their manufacturer, it would require bridging studies to ensure appropriate validation and equivalency, and the last time Northwest did a technology transfer with Fraunhofer, the process took close to 18 months. I understand that it’s just wishful thinking, but do you really think that this transfer would take place during negotiations? That Linda would just hand over her baby based on big pharma’s good faith negotiations? I doubt it. No, a deal would probably had to have been reached at least a year ago, and that would have been before results were known. Again, I doubt it . . . . but keep dreaming, it was entertaining.
DCVAX®-L MANUFACTURING AND SERVICES AGREEMENT
This Amended and Restated Services Agreement (this “Agreement”), originally dated April 1, 2011 is entered into, effective as of January 17, 2014 (the “Effective Date”), by and between Cognate BioServices, a Delaware corporation (Cognate”), and Northwest Biotherapeutics, a Delaware corporation (“NW Bio”).
6.1 Term
This Agreement will remain in force until the later of seven (7) years from the Effective Date (the “Term”) or five (5) years after the first commercial sales of DCVax®-L Products pursuant to a Biologics License Application or marketing authorization (not a compassionate use, hospital exemption or similar authorization), unless terminated earlier pursuant to Section 6.2.
6.2 Termination
Either party may terminate this Agreement in the event of a material breach by the other party which remains uncured after notice of such breach for a period of thirty (30) days in the case of a monetary breach, or a period of one hundred twenty (120) days in the case of a non-monetary breach that is material to the contract taken as a whole.
Flipper, that is so true. I shared a few months ago that my grandfather died of GBM, and he used the Optune device. My grandfather was not particularly vain, but he was a proud man and still had a full head of hair, so when he had to shave his head to attach those electrodes, it literally crushed him. I mean you could almost see the life sucked out of him when he looked at himself in the mirror afterward. For the first time, I think it really struck him that he was sick, because now he actually looked sick. I had my head shaved right along side of him to show support, but it didn’t have the effect that I had hoped. In fact, it may have made him feel worse looking at my bald head too because he just shook his head and looked at me with sadness.
People can say what they want about the “quality of life,” but losing ones hair is a big deal, whether it’s from shaving or chemo. After that day, the day he got that “damn contraption,” (as he called it) he was never the same, never had the same vigor, and he seemed relegated to being sick. I think he had to shave his head twice a week, but he got an electric shaver and he said it only took a few minutes.
Nice post. You’re right, Linda will not sell NWBO for $5B-10B. DCVax is a platform technology that is capable of treating not only most cancers, but also (potentially) auto-immune and many other diseases, so to think its price should be compared to limited CAR-T technology, is ridiculous.
While I think Linda is not looking for a buyout and is certainly prepared to take Northwest to the next stage of growth, knowing her background, I have some doubts that she will fight to stay independent if the right offer comes along. Northwest Bio only has a dozen or so employees, no sales or commercial infrastructure, and a contract manufacturer, so it’s really set up to be sold. If/when DCVax proves itself in ndGBM, the buyout offers certainly will come, since Big Pharma is always looking to add a hot new immunotherapy to the mix. BP is well aware of the difficulties that clinical-stage companies face when transitioning to a commercial-stage company and their offers at this stage may be less than Linda would accept, but you never know.
I can’t help but wonder what someone like Dr. Roger Perlmutter, (the president of Merck’s research labs who is currently running over a thousand clinical trials just studying Keytruda) thinks of the way tiny Northwest Bio has conducted its clinical trial program for DCVax, versus what the true potential could be in Merck’s hands. Based on their understanding of this potential, and their commercial success with Keytruda, it wouldn’t surprise me if Merck put a very solid offer on the table ($20B-30B) if Northwest presents outstanding data.
As an investor, my preference is for Northwest to remain independent and to partner combinations with big pharma. But I would think that almost everyone else, especially scientists, physicians and their patients would probably prefer to see DCVax in the hands of Merck or another big pharma company with the capabilities and resources to allow DCVax to reach its potential in the fastest time possible.
In an interview at ASCO, the chief development officer for Pfizer Oncology, Chris Boshoff, said something of interest that may portend good news to Antares investors:
“Why are we developing another checkpoint? The current checkpoints are essentially all being developed as intravenous infusion. This one is being developed specifically only as a subcutaneous administration, so it will be a prefilled syringe. The current regimen is once every four weeks, but our [pharmacokinetic] data indicates we potentially can go once every six weeks. Having a subcutaneous, prefilled syringe as a backbone to targeted therapies we feel could optimize the way we develop immune checkpoints in the future.”
I’m not speculating that Pfizer is going to contract with Anares for this, since Pfizer is building their own state-of-the-art sterile injectable pharmaceutical production facility in Michigan, but it indicates where the industry is headed and that Antares’ expertise is likely to be in very high demand.
https://www.biopharmadive.com/news/asco-19-pfizer-immunotherapy-targeted-cancer-drugs/556067/
I remember reading this article over a year ago but it seems relevant now. I’m pretty sure that Merck isn’t alone in this thinking.
BTW - I believe Linda’s plan involves duplicating the commercial success of Keytruda by getting DCVax approved as a monotherapy in multiple indications, as well as partnering with multiple big pharma companies. I think there is a belief across the industry that the future of cancer medicine lies in combinations. If DCVax proves itself in glioblastoma, (one of the most difficult cancers and where ALL BP have failed) Linda’s dance card will be full, and Mr. Duffy will be earning his salary and options.
Drugmakers struggle to find immunotherapy combinations for cancer
David Crow in New York MAY 30, 2018
After decades of frustratingly slow progress in discovering new drugs to battle cancer, the breakthroughs have started to come thick and fast. Futuristic cell therapies from Novartis and Gilead Sciences can re-engineer the body to attack tumours, while a drug from Loxo Oncology produces spectacular results by zoning in on cancer genetics. The annual meeting of the American Society of Clinical Oncology (Asco), the world’s largest cancer conference, has become the main forum for drugmakers to chart their success. As the pace of discoveries has quickened in recent years, it has turned into a kind of rock festival for the pharmaceutical industry. This week, 30,000 doctors and pharma executives will again assemble in a huge conference centre on the banks of Lake Michigan in Chicago for the meeting to pore over results from hundreds of clinical trials. The biggest advance has been the arrival of immunotherapy drugs, known as checkpoint inhibitors, which remove brakes in the immune system so it can fight cancer as it does other foreign invaders such as viruses. The medicines, which wowed the audience at Asco in 2014, raked in $10bn in sales last year for Merck of the US, Bristol-Myers Squibb, Roche and AstraZeneca. This year’s meeting was supposed to be another one for the ages, when pharma companies would finally start to prove a popular theory which holds that combining two immunotherapy drugs into one treatment can dramatically boost survival rates. While a minority of between 20 and 30 per cent of cancer patients do extremely well on immunotherapies, most do not. Drugmakers have been trying to push response rates higher by testing cocktails containing two medicines targeting the immune system. Thousands of trials are under way. However, the company that was supposed to be this year’s headline act will be conspicuously absent from the main stage. Incyte, a US biotech group, had hoped to prove that combining its experimental immunotherapy with Keytruda a leading checkpoint inhibitor made by its Big Pharma partner Merck would boost survival rates in patients suffering from melanoma and other common cancers.
But after announcing the failure of its closely watched Phase III trial earlier this year, Incyte’s investigators will instead take to the podium with a presentation that tries to unpick why the approach was so unsuccessful. Every year Asco has an advance of the year said Brad Loncar, founder of the Loncar Cancer Immunotherapy Exchange Traded Fund. This year was supposed to be the year of combos, but it hasn’t materialised as quickly or as robustly as anyone would have hoped. Outside of melanoma, the only combination approach that has been conclusively proven to work involves twinning a checkpoint inhibitor immunotherapy with chemotherapy, a treatment that has been used to fight cancer for more than 70 years. Last month, Merck unveiled a large trial showing this cocktail can dramatically improve survival prospects for people suffering from the most common form of lung cancer, putting it on track to become the standard first-in-line treatment for these patients. However, the inclusion of chemotherapy in the mix means patients must still contend with its brutal toxic side effects, such as hair loss, vomiting and anaemia. The holy grail is still finding two immunotherapies that can manipulate the immune system so that it does all the work, meaning chemotherapy can be discarded altogether. But a crop of studies due to be presented at this year’s Asco meeting suggests there is still much more work to do. . . .
The patchy progress in finding the right combination supports the view of those oncologists who think drugmakers have started taking foolhardy scientific shortcuts in the hope that they will strike lucky and find a blockbuster treatment. Merck made a big bet on Incyte’s failed combination effort, in a rare stumble for a company that has developed its own immunotherapies with scientific rigour, even if it has meant sacrificing some early commercial success. Mr Loncar identified two problems with the Incyte and Merck collaboration. First, there was scant proof that Incyte’s drug was effective in fighting cancer. Second, the companies charged into a series of large and expensive trials based on data from a handful of small, early-stage studies, without doing the necessary mid-stage groundwork. Roger Perlmutter, Merck’s top scientist, said the company would focus its future efforts on combinations where each of the drugs has been proven to work separately as a “monotherapy” before testing them together.
I’d prefer to combine mechanisms where both parts of the combination have activity by themselves, he said. Incyte’s drug] did not have single-agent efficacy, which was always worrisome. Asked whether that meant Merck could scale back any of the roughly 400 combination trials it has under way, Dr Perlmutter replied: We review them all the time based on new data that comes in; we are always looking at them and thinking about them. However, Pascal Soriot, chief executive of AstraZeneca, which is trialling its own immunotherapy combo, predicts companies will still move quickly because the lucrative field is so hotly contested. It’s still a very competitive race and people are ready to take risks, said Mr Soriot. Of course, we are going to be looking for monotherapy activity, but if we have a good biological rationale, we may still take the risk with a combination
https://www.ft.com/content/d39afa5e-6066-11e8-9334-2218e7146b04
Sorry - it looks like this article may be behind a pay wall now at the Financial Times.
You’re funny Dr Bala. Yes, I’m watching you. Actually, the eye is a reference to my alias, which you probably know means “far sighted.” I’ve always been a big-picture person, and that also reflects my investment style, which tends to be long term. Aloha.
sentiment, I agree with your timelines for the most part. The normal review period for the FDA is actually about ten months, but as you say, priority review can be six months. I’m very optimistic that once the data is revealed, that a lot of things are going to be different for Northwest Bio, and the new, shorter regulatory pathways will become available to DCVax. And while I’m also hopeful that much of the pre-BLA work has been completed, and that RTOR would be available, I’m not as confident about either of those.
CDER 21st Century Review Process Desk Reference Guide
https://www.fda.gov/media/78941/download
FDA & EMA Joint Report on Early Access Pathways
AUGUST 27, 2019
FDA recently published in coordination with the European Medicines Agency (EMA) a report from a joint FDA-EMA workshop with stakeholders on supporting product quality development in early access approaches (see the report and workshop materials here). Presentations from each of the speakers, panel and break-out sessions are also available.
More here: https://regulatory.parexel.com/regulatory-blog-2/fda-ema-joint-report-on-early-access-pathways
Stakeholder workshop on support to quality development in early access approaches, such as PRIME and Breakthrough Therapies
The aim of this workshop was to discuss scientific and regulatory approaches which could be used to facilitate development and preparation of robust quality data packages, to enable timely access to medicines for patients whilst assuring that patient safety and product quality are not compromised.
Participants looked at specific industry case studies covering chemicals, biologicals and advanced therapies and experiences across different regions.
EMA and the United States Food and Drug Administration (FDA) launched PRIME and Breakthrough Therapy schemes to strengthen their support to the development of medicines for unmet medical needs to help patients to benefit from these therapies as early as possible. This workshop is a joint collaboration between EMA and the FDA.
EMA has published a report on the workshop, containing recommendations from participants on next steps and areas to be further explored by EMA and the FDA.
https://www.ema.europa.eu/en/events/stakeholder-workshop-support-quality-development-early-access-approaches-such-prime-breakthrough
Hi H2R
I wouldn’t read too much into the volume today. The “Bigger” block likely took some time to negotiate, and I think Idunno is correct that Carson Block and his gang of front- running thieves were as surprised to see that 15M block as the rest of us. And as far as the shares being locked up in “longs” hands now, I wouldn’t be so sure about that either. Bigger isn’t the White Knight that some here seem to think.
Good to know you are still around too gigi. Yes, it was clearly a hit piece. I’ve followed Mako for some time on SA, and that’s what he does, he shorts and writes the bear case. I have to say this report was rather weak compared to some of his other reports, so there may be something to CN’s theory. The comments on his articles are often mixed but it looks like most of the comments on this article were pretty one-sided and disagreed with him. I was just surprised that no one here had a comment about it, and miss the good ol' days.
Another article by SoS - Sales Projections for Xyosted
Antares: Update on Sales Projections for Xyosted (ATRS, $3.30, Buy)
https://smithonstocks.com/2555-2/
A model is only as good as its assumptions. At least Larry Smith admits that his model has some flaws, (as most of ours do) and his numbers are not set in stone, and I appreciate that, but I still think he’s being too conservative. I know it’s still very early in the launch and it’s difficult to project sales at this point, but simply following the current trend line, the sales in Q3 should be around $7.5M and about $10.5 in Q4. That would put annual sales closer to $23M instead of the $18.8M that he estimates. Going forward, I would expect sales to accelerate once insurance coverage increases, and physicians become more familiar with Xyosted, so next year’s sales should certainly be higher than the $54M his model shows. Even if it only follows the current trend, it should still be over $70M.
ou71764, I agree that his analysis is decent, but he remains far too conservative. I guess it’s just the way the game is played. Analysts mostly rely on the company for “guidance” and the company gives conservative guidance to ensure that they can meet or beat the Street’s expectations. Antares’ management guided revenues this year around 95M-105M, and all of the analysts projections were within that range. (okay maybe one was 89M?) This month, the company raised their guidance range by 5M and all of the analysts (like sheep) raised their projections within this range once again. I think we can see with the way Xyosted sales are headed, and the way that the full Epipen launch is beginning to take off, that management is going to raise their “guidance” once again next quarter.
(BTW - I posted here six months ago that management was being too conservative, and my model predicted ~120M for the year, which should actually be pretty close)
In the bigger picture, I think you’re right, and I’ve been saying the same thing . . . patience is required, but it will be rewarded, and possibly fairly soon. I think we’ve been seeing some big funds slowly repositioning themselves over the past few months when they realized that the Xyosted launch was actually going to be successful, and Antares wasn’t going to run out of cash. I know some people are talking profitability soon, but I’m simply expecting cash flow positive, with some increased spending going to R&D in the new facility.
Ned Sharpless GBM Awareness Day Speech transcribed
I was really elated to be invited to this. This is really a personal effort to me. I would really love to see some progress in GBM. Probably no cancer pisses me off more than GBM. You know it would be great to relieve it. At the FDA we would love to see those ideas come in so that we could approve them to help people with GBM. So this is really something that I was looking forward to doing. Thank you for having me. I’d like to thank Senator Graham and Senator McSally as well as Senators McConnel, Warren, Sinema, and Markey for their sponsorship of this resolution for this Glioblastoma Awareness Day. It’s a great initiative. And based on my experience, as Comprehensive Cancer Center Director, and cancer researcher, NCI Director, and now Acting FDA Commissioner, huh what a mouthful, I had a chance to get various insights into this disease and see it from many perspectives. I certainly have had the experience of talking to patients and loved ones about the problems with therapy for GBM and the bad outcomes. I know as a doctor how tough this disease is to treat and how limited our options are for our patients. As someone who has directed the resources of the Federal Government to topics related to cancer research related to public health, this cancer, GBM in particular is where I’d like to see us do more to make more progress. Because I think we have it. We used to say at NCI, this is a special time for cancer research. We’ve made a lot of progress in a lot of places, and remarkable pace, but unfortunately GBM is not one of them. So given my recent role at NCI and FDA, I’ve been keenly aware of how hard it is to develop new therapies for this disease. It’s really a place where we really haven’t had the progress we’ve had in other cancers for several reasons. GBM is a cancer where we have this blood brain barrier problem which is an issue, and has limited the efficacy of agents in GBM . . . In my new role at the FDA I can help the development of new therapeutic approaches and diagnostics for GBM based on the science funded by NCI and other sources. Although we are currently in an era of unprecedented drug development for many cancers, progress has lagged in GBM. The therapies we have are too toxic. We recognize for Glioblastoma, it’s not really life threatening, it’s like personally threatening, self threatening. Its a disease that these therapies can rob patients of so much. Patients bear the burden of both a life-threatening illness and a progressive neurologic disease that affects their ability to work and to be with loved ones, and every sense of self. In recognizing the challenges, and the uniqueness of this disease, the FDA has been committing to putting all hands on deck approach to supporting drug and device development aimed at treating patients with GBM. To that end, we’ve worked closely with the National Brain Tumor Society to co-sponsor workshop aimed at how to best design clinical tails and measure outcomes for patients with GBM. We continue to support this partnership in the form of twice yearly round-table discussions designed to bring together the FDA and the academic community to discuss the challenges to produce drug development in GBM. The FDA has participated in the planning the informal discussions with the aim of clarifying regulatory issues and providing our expertise. And the FDA’s Oncology Center of Excellence has established a mechanism to ensure the disease area of expertise is provided when reviewing all products intended to help patients with GBM as well as ensuring consistent advice is provided throughout development on this important topic. The FDA also has several methods to streamline and fast-track review of investigational therapies for a lot of life threatening orphan diseases, and I can think of no better candidate for those kinds of mechanisms than GBM. These include the break-though therapy designation, fast-track review, priority review,and programs designed to move the products through the review process rapidly, as well as accelerated approval where drugs are allowed onto the market based on the activity at certain end points. We’re hopeful that progress will be made in this disease as multiple new technologies are brought to bear on this problem, the new exciting immunotherapies, some new targeted therapies, new types of careful clinical trials with adaptive design and novel to better find agents more quickly and the better use of radiation therapy, surgery, novel devices, imaging, and other therapeutic approaches in this space. It is my belief, you know with all this science and great efforts brought to bear, we will build on previous work as well as the new ongoing science to take the significant but in my opinion too incremental progress we’ve made in this disease thus far and move it to even better therapies that will really make a difference in the lives of patients with this disease. And you know, no one would like to see this progress more than me in that regard. So thank you for the opportunity to speak tonight and let’s get this done.