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I read the Feuerstein article. It is similar to what we've heard before:
I asked [Clark Chen, chair of the neurosurgery department at the University of Minnesota School of Medicine] to review the DCVax study published in JAMA Oncology.
“The authors should be congratulated for conducting a study of this magnitude,” but the results are “uninterpretable” because the analysis was not pre-specified when the study was started in 2007, Chen said.
Making the argument we've all heard before:
In a prespecified analysis of its primary efficacy goal, the DCVax group went a median 6.2 months without their brain tumors returning compared to a median of 7.6 months for patients offered a placebo.
DCVax performed worse than a placebo. The study failed.
Adam did seek a comment from Liau:
These results are “persuasive and valid,” Linda Liau told me. Liau is the principal investigator of the DCVax study and the chair of the department of neurosurgery at UCLA.
In response to questions submitted by email, Liau told me she believes the study and its positive findings should be considered “prospective” because the statistical analysis plan was “drafted and submitted to regulatory agencies prior to data lock and unblinding of the data.
I agree totally. We're up from the 60s. A bit of buy the rumor, sell the news, coupled with a hit piece. Very significant fundamental developments with JAMA. More to come. I really don't get the complaining.
BTW, I haven't read the STAT piece, but it seems to me that even the bears have gone from:
it's a fraud and DCVax will never hit its efficacy endpoints => DCVax will never be published or approved => DCVax will never be approved => DCVax will never be approved except in a (large) subset of patients ....
that trend looks good to me.
From my perspective, things are tracking fine. I don't expect a stock to be up every day but the trends, both fundamentally and with the share price, are positive. Judging by the event / milestones that many on this board referenced, there's more to come.
I'm sure it rehashes the same talking points. The only recent incremental information is that (a) JAMA put its reputation on the line and (b) the therapy is on the radar of many more practitioners.
Yes, it’s possible. There are also intermediate steps that strategics like to take, like co-sponsoring trials.
I think we’ll see a push to commercialization in the UK very soon.
The use of external controls will remain controversial right up to any regulatory approval and this won’t come just from some investors/pundits/bears but also from some in the medical community.
The doctors that I spoke to who participated in the trial are universally and strongly behind the therapy. But I’ve spoken to others, not involved in the therapy, and was surprised to hear they were generally supportive. Safety + unmet need is a strong motivator.
The real transformative opportunity for DCVax is when used in combination. But those trials never get done if DCVax doesn’t get approved. A 2nd Ph3? Similar problem.
The NovaCure device has role, but it would be a mistake to bring further DCVax development (combos/other cancer types) to a halt because NovaCure serves a certain subset of patients.
Any regulatory decision brings a certain set of consequences. Approval seems like the better choice if the objective is to serve the interests of cancer patients.
Even the filing of lawsuits tends to quelch bad behavior. May 10 was a little too exciting. Next time we're up 100% better if it sticks.
Seems like we should be close on the commercial manufacturing license for Sawston and once that's done, the MAA submission. With an accelerated UK approval, could be commercially active in the UK in 2Q/3Q.
Makes sense. What about:
10Q / Part II - Other Information / Item 1. Legal Proceedings
The Company is currently considering possibilities for legal actions against third parties who have attacked the Company.
Milestones - so what are the next milestones that this board anticipates?
Let's limit it to fundamental achievements, not a buy-out since -- unless someone has some inside info that is going to get us all in trouble -- that's just pure speculation.
These types of points are how therapies get approved. It is way more than just statistical debates. Thanks for sharing Bright Boy.
If we're hitting milestones and have a strategic asset those things happen, but I really don't think about them much.
Not that concerned. If NW can't work around any IP then they are the natural licensee anyway. UCLA isn't going to into the pharma biz and having IP around Muricidencel and FlaskWorks is critical.
If what we're hearing on combinations holds up to investigation, then the negotiations might be between big pharma and UCLA.
LC, nice to hear from you!
There is some truth in everything you say but in 25 years I've never had a perfect investment. It's always comes down to judgement and then being mentally flexible as the information develops. On the most important information -- the trial data and how that data would be received by the medical community -- is clearly favorable.
The stock lost ground recently as the markets went from speculative to risk adverse. If we were still in a bull market, the stock would be 3+.
Some things, like the board stuff, need work. The presence of institutional investors fixes that and, historically, it hasn't been in my interest to address it.
TTFs aren't used widely enough to cause an approval issue, in my view. Experimental treatments are experimental.
So, why don't you tell me about your perfect investment? I would love one of those :)
First, thanks to everyone for the well wishes. I wish everyone the same, especially the bears because they'll need it.
Mostly, bear markets are about not losing money, so my exposure is low. My most important recent investment decision was to get overall defensive once inflation ticked up about a year ago. I expect to redeploy in 2023 into super high-quality companies (e.g., GOOG, which now has activist TCI exerting pressure) and cash rich life science companies. But I'm disciplined on price.
As far as small public companies, I think OTLK will be a big winner in 2 - 4 years, but it needs capital soon, so keep an eye on it but don't buy it until they have sufficient capital.
I tried to invest in crypto but couldn't not develop an investment thesis. I kept concluding that it looked more like a Ponzi than an asset, so dodged that bullet. I am looking at GBTC now since the NAV discount is large, but still not convinced.
I have positions in large companies, like Hess, Valero, Humana, McKesson, UnitedHealth, Taiwan Semi, but some of those are board member relationships and I wouldn't say I have a great edge, so I wouldn't read much into it.
I have some privates - a vaccine, a battery and a SaaS company -- that seem to be doing really well and keep adding capital. Likely Sanofi will buy the vaccine company next year. Also, I have some oil & gas development projects and an interest in an electric power facility, and the winds at our back on those.
I guess is msg will get removed by the admins unless I mention one other name. Have I ever mentioned I have a position in NWBO? Well, I do.
After I sold too much ISRG early, I stopped putting too fine a point on valuations of regime changing companies. I just track if the evidence is consistent with my thesis and let the winners run. One caveat, if the company needs capital, I may recycle some.
Thanks Doc.
I confess I was expecting the post JAMA bear argument to shift to something else. There’s always a ‘something else’ so why not make that kind of argument?
I find conversations with those that disagree with me to be more interesting, so I’m happy to engage. But I also I know if I was short this stock based on a data dredging argument, I’d be feeling things are lining up against me. I personally know many of the best-known investors on the planet and they’re all willing to change their minds when presented with evidence.
Ex, thank you for your thoughtful reply. From your recommended paper: “Wittes encourages consideration of changes in long-term trials, as medical knowledge evolves or when assumptions made in design of the trial appear questionable.” Medical knowledge regarding PFS measurement did evolve, and the FDA mandated cross-over arm made a randomized placebo O/S comparison impossible.
But, I’ll admit, this trial has been unconventional, and you have an argument. I thought carefully about the issues you raise but concluded differently. I don’t think knowing that PFS failed means you know an O/S comparison succeeded.
JAMA also considered these questions and put its reputation on the line.
I've raised your exact point with other academic neurosurgeons, and I’m not hearing significant concerns. What am I hearing? “Is it safe.”
Regulators are swayed by the science and data but also by reputational risk and patient stories. JAMA and the medical community are supporting this treatment.
I guess we’ll never agree to agree but you must admit, the trend is against you.
Some of what I know comes from conversations with people in the field so, no, there's not a written statement I can reference. But it's apparent to me that skepticism is dissipating in the medical community.
Stupp wouldn't be an author on the JAMA paper because his patients weren't part of the trial. That's standard. But after seeing the unblinded results he thinks the therapy has merit according to what I've heard from others.
Ex, I've said previously that I thought the PFS endpoint failed, and it was at the core of the enrollment halt.
It's a subtle point but changing endpoints itself does not invalidate statistical conclusions. What matters is data dredging, which often is associated with changing endpoints but doesn't necessarily have to be. I got to think you, and other apparently smart people, understand that. So, I just don't get why you keep coming back to this point.
I've also said previously Stupp would support the trial and that we'd get a publication in a highly respected academic journal, like JAMA. I've also said that neurosurgeons not involved with the trial are very interested in the therapy (I gave one example, but I've had conversations with others).
A most important characteristic of the best investors is the ability to clearly judge new information, change your mind when the data conflicts with your prior (as I've also stated, I was short the stock once), and go big when it conforms.
Which way is the information trending in this case?
yes, sarcasm. My Dr friend knew the dcvax approach incredibly well. I've been studying dcvax for 10+ years and he knew things I didn't know.
You're reading it wrong. He is saying "<5%" is SOC. DCVax much better. Ergo approval.
But then I told him about the concerns voiced by Feuerstein, MidwestHedgie, HyGro, dr_lowenstein, ... and it totally changed his mind. He’s never using it on his patients.
Had lunch the other day with the Neurosurgery Department Head from one of the top research hospitals in the country.
He didn’t participate in the trial, but he knows Liau and her research very well. I told him I expected publication of the trial details soon.
His comment re DCVax: “I know the therapy well and I know it works” and “look forward to reading the details”.
JAMA Oncology - in the Top 10
https://www.scimagojr.com/journalrank.php?category=2730
I've considered all of this, and I am long. The information in the paragraph you cite and been discussed on this board ad nauseum.
The squirrel is smart
In light of yesterday's AdCom vote, we see [FDA AdCom Backing of AMLX AMX0035] as a significant positive for the biopharma industry, particularly companies focused on developing therapies for severely debilitating and fatal diseases, where there are high unmet medical needs and few, if any, treatment options. Types of companies that we believe stand to most directly benefit include those developing treatments for: (1) neurological/neurodegenerative diseases; and (2) rare, orphan diseases (i.e., those diseases affecting 200K persons and less in the US) that are fatal.
- Graig Suvannavejh, Ph.D., Managing Director, Mizuho Securities
...and for those who are going to comment that the FDA's Peripheral and Central Nervous System (PCNS) advisory committee is not the applicable committee -- yeah, I know that -- but organizational perspectives filter across organizations.
I beg to differ; I think it is very good news!
Impressive.
At ASCO, I visited with the docs involved in the DCVax trial. They are strong endorsers and think it's great for patients. They thought there was little doubt about a UK approval. I've also had some discussion with leading neurosurgeons in the US, but that were not involved in the trial. They are not familiar with the recent data, so a journal publication is definitely important. One of them was very familiar with DCVax and believes the approach has clinical benefit, but just didn't know about the recent data.
There are a number of smart posters to this board. I've been quite busy with some other investments and NWBO is slowly progressing, so I didn't have much additive to say.
Hi all, the good news is I'm still alive :)
Approved earlier this year:
On February 7, 2022, FDA had approved Vabysmo (faricimab-svoa), an injectable therapy for those with wet age-relate macular degeneration (wAMD) and diabetic macular edema. This approval is especially interesting considering that it is the first drug of its kind to be approved for both wAMD and diabetic macular edema.
As I noted, this will be a premium priced product, no different than Eylea.
A journal publication is a bigger deal that ASCO in my view... and I'm guessing that will follow ASCO in short order. After that, MAA filing. We've got catalysts.
I like peanut butter and jama.
Tumor Treating Fields - Novocure
What's odd about Midwest Hedgie is that his 13F portfolio is less than 10% invested in Heathcare. Must not have that big a Heathcare edge.
I did all my survival advantage guesstimating before. At this point, I'm waiting on a journal publication.
I'm more optimistic.
(+) If no publication before ASCO, then publication after ASCO.
(+++) Then MAA filing in the UK.
(+) Medical and patient advocacy group excitement will continue to build.
(-) A financing at some point but not sure when. Hoping it will be on better terms (better for you/worse for me).
Score: 5 to 1 => I think it can rally.