The paper you cited today in post #71944352, prepared by Klinker and Bauer et al, is a preprint ie. unpublished and non-peer reviewed. This is NOT what Matthew Klinker himself recommended to industry for insights in the recorded Townhall Series Q&A he did on the topic of CMC (Chemistry, Manufacturing and Controls) in Cellular Products in June last year (if you go to my post today, you will see the link I posted in reply to @Stellowe, or you can search for it in the FDA website). Dr. Klinker clearly asked people to refer to published and peer-reviewed material.
To answer a question at the 30 minute mark of the recording, as read out by his FDA colleague, on whether it is necessary to demonstrate that potency tests measure an attribute associated with clinical outcomes, Dr. Klinker mentioned specifically, “Just to be clear, they (federal regulations for drug approval) DO NOT require that an attribute measured by a potency test be associated with clinical outcomes.” My transcript of his full answer follows:
Matthew Klinker: “So looking at product attributes (relationships) to clinical outcomes can be a good indication that the attribute is relevant to potency. This is no simple feat and federal regulations have quite a bit of flexibility regarding potency tests. Just to be clear, they do not require that an attribute measured by a potency test be associated with clinical outcomes. But for products that are generally not well characterised, evaluating potency attributes’ association with either clinical or non-clinical outcomes CAN BE a useful way to help you figure out what attributes are meaningful. While either non-clinical or clinical outcomes can be a useful way to figure out what attributes are meaningful, it’s important to remember, however, a statistical relationship alone should be supported by additional data establishing a mechanistic relationship. It really has to make sense why this attribute is related to potency.”
So, consistent with my understanding of how FDA drug approval works, which requires a demonstration of safety and efficacy, Dr. Klinker effectively said that you do not also need a full understanding of the mechanism of action to get an approval. You can still spend your time thinking and researching the MoA, but that’s not how I would like to spend my time now as an investor even if the company CAN do that, given what Klinker made so clear in the above recording. I hope you understand me as saying that even though I am an avid learner, it is unnecessary for you to waste your time trying to teach me or getting me to understand what is in the unpublished preprint now. With the limited time that I have in a day, I do not think it is the best use of it. Thank you for the offer nonetheless. If you want to teach the company, perhaps you can send them an email. I have done that in the past with board members on corporate governance issues.
The other thing that you and @Pfeiffer1982, with due respect, have been spending time on, is the ODAC notes in 2020 outlining Dr. Bauer’s issues with the Phase III trial. There is the (incorrect) assumption that I have not read the posts containing the excerpts which I actually really appreciate both of you putting together or referencing, (in fact I have read parts of the actual notes as well), but I refer you to the market release by the company right after the Type A meeting, in September 2023, which says that the only key remaining issue is the potency assay data. I presume you do not work for the company so I am not sure why in 2024 you are still talking about the 2020 notes when many conversations would have taken place between the FDA and the company, unless of course you are assuming that the company was not truthful in the Sep 2023 market release in relation to what is in black and white in the CRL and then discussed in the Type A meeting. I actually have reason to doubt that presumption, simply because while Dr. Krause did not help achieve the approval last August, he is a person known to have departed the FDA with another colleague in a rather high profile way, which the public took as a sign of his integrity, and Dr. Krause said (I think at the end of August in a conference call but correct me if I am wrong as to when he did) that the CRL in early August no longer mentioned efficacy as being an issue. Presumably he was trying to say, that the long term data that the company added in the resubmission did carry some weight, in moving the needle. What remains, again you can choose not to believe what was clearly stated in the Sep 2023 market release, is the potency assay data. In the same recording above, and just before the question we spent time above discussing, there is a question about acceptance criteria for the potency assay. Klinker said that the reason why you are well advised to start working on the potency early in the trial, is so that you can “know what an effective commercial product” will look like further down the line, ie. a product assurance issue. This is how I understand the issue being worked on as it currently stands and I agree with @otherperspective that there are clearly missteps by the company.
I have been posting as a very long term investor (again you assume incorrectly that I have only been involved in the last couple of years - I remember the Caphalon association with the company and how the heart assets became part of TEVA and sold back to the company for very little money) trying to gauge the chance of success of this latest twist in the quest for data by the FDA. I hope that I have not given the impression that I am saying they will succeed - I am not giving financial advice. My sense is and I have stated this a few times, the job is still not done yet but I think they are close to finishing. Some of my heightened interest is predicated on my son’s acute ulcerative colitis which saw him hospitalised for 8 days after going to ER in 2021. The presentation of symptoms, as some of you may know, is remarkably similar to GI GVHD.
When posters here imply that others are suffering from confirmation bias, I wonder, along the same line, what gives them the confidence that a thesis lifted out of the ODAC notes in 2020 continues to be correct in 2024. Focusing on the dreadful share price performance in the last few years could be like looking at the rear view mirror, at a historical success of a strategy that may be predicated as much on the difficulties that came out of the first CRL, as it may have on the company’s need for capital and how that need had fulfilled the shortsellers’ prophecy almost without fail. That being said, without a pharma partner, it is not a hard prediction to make.
The last thing I’d like to receive is a lot of likes for this post. It would be nicer for you to press the light bulb, to say that it has given you some food for thought and no more. Social media can be poison these days - I have no desire to control any narrative or prove that I am right. Just saying. (You won’t see me for a very long time, maybe never again.).
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