Coen

.

[Not Jerome Powell @alifarhat79]

Trump: I’m attacking Iran. I’m not attacking Iran. I’m attacking Iran. I’m not attacking Iran.

Markets:

[Coen @CoenS26]

@JerryLee2248 @JackMan724444 Statistically you would expect some cancer cases, market is too dumb to realise

[Adam May @A_May_MD]

Absolutely KEY $ABVX point attached here that I have so far seen absolutely NOBODY mention.

Opportunity abounds.

[deathTouch @deathtouch2k]

$ABVX As a follow-up to a few posts that I saw regarding the perceived elevated rates of NMSC and malignancies in the 50 mg arm specifically in the phase 3:

A few thoughts:

1) The phase 3 50 mg dose is actually a small minority of the patient years of safety data acquired -- the much larger dataset for that dose comes from the phase 2b long-term open label follow-up, which can be reasonably pooled with the phase 3 results given the same dose and detection protocols (Note, we have seen some analyses that pool 25 mg and 50 mg arms. We would NOT recommend doing this as it is not fair to claim that the risk of developing cancer in the 25 mg arm is known to be the same as the 50 mg arm). Pooling 50 mg phase 2b and 50 mg phase 3 data sets yields a much lower rate of events across the board. (I suspect it was just a bit of bad luck on the smaller phase 3 dataset for the 50 mg dose in isolation, see below chart for what we've been working off of after integrating these phase 2 data -- note there are some assumptions that go into this but the variability should be pretty de minimis);

2) Two ways things generally cause cancer: DNA damage from some oxidative/radiation/something else source that damages DNA or inhibits DNA repair mechanisms at their core OR substantial or highly targeted immunosuppression. Because both of these events are total exposure related, typically events accelerate over time. The phase 2 had the much longer follow-up with fewer patients whereas the phase 3 had more patients followed up for less time. The phase 2 had a very low number of events, and the phase 3 50mg dose was the only arm that had an elevated set. A priori, if the drug was a carcinogen, we would have expected the opposite: that the phase 2 would have a higher incidence/100 PY than the phase 3 given the individual patient exposures on a cumulative basis to such carcinogens are much higher in the phase 2 than the phase 3 in addition to the idea that there is a delay between when the carcinogen can cause the malignancy to when it can be detected (and T=0 is always the first instance in which that timer could start). Also, if the drug was as immunosuppressive as would be needed to cause cancer, you would expect to see a boatload of opportunistic infection before you'd see the cancer signal -- we see none.;

3) Pre-clinical testing confirmed that the drug is actually an anti-proliferative -- we would have expected the drug to be protective against tumor growth, not stimulating it;

4) No consistency or clustering for any cancer type at any time point;

5) NMSC carries a much different (lower) risk profile than other types of malignancies since they are caught very easily and have a low rate of metastases, and are seen at a massively disproportionately high case numbers relative to other types of malignancies (also included in the bottom table following pooling of the 50 mg arm), so FDA is less concerned about it than non-NMSC;

6) To warrant a black box, the FDA usually requires, at a minimum, consistency of preclinical and/or striking clinical datapoints such that careful consideration must be made to determine if the benefit/risk profile inverts in a subset of all patients that may receive the drug. In this case, we not only have completely disparate and conflicting datapoints, but we even have one data point relating to the MoA and pre-clinical data findings that suggest the drug should have the opposite effect. In addition, black box decisions are not made in isolation. They are heavily debated back and forth between the company, internally, require a lot of internal consensus on establishing causal link, and are not made in a vacuum to unmet need and efficacy;

7) UC patients have an elevated rate of inflammation (by definition) and, in turn, elevated rates of cancer compared to healthy individuals (~+.5 events/100PY vs non-UC). Obefazimod is now a proven highly effective therapy that leads to robust endoscopic remissions and attenuation of much of this inflammatory effect. I would hypothesize if you ran a large enough study and followed patients for long enough, you would find that there would be a cancer benefit from the drug secondary to the disease control that it would afford. The weight of this potential benefit (which makes sense given the pathophysiology) must be considered against the risk of the agent itself causing cancer (for which we have no reason to believe it actually should cause cancer).

[Adam May @A_May_MD]

I keep hearing people referring to "7" cases of cancer in the high dose arm for $ABVX. I get it - that's what they technically showed in the table, but in observing a lot of conversation about this I gather that people don't actually realize what really matters there. I am strongly of the opinion that there are really only 2 malignancy cases that matter for adjudication - the prostate cancer and breast cancer cases.

I initially started talking about these cases as "the 2" cases from the very beginning because I assumed that everyone would be on the same page that these were the only 2 that mattered...but I've found that people really are considering this as a case of *7* full blown malignancies in the 50mg arm...This is just not correct.

Let's break this down.

First of all, they're counting "colonic dysplasia" in this table as one of the "malignancies". I cannot stress this enough: Colonic dysplasia is, by definition, LITERALLY not cancer. This is actually an unequivocal point that I don't understand how it could even be up for debate.

"Dysplasia" is a "precancerous" lesion. Cervical dysplasia, colonic dysplasia, melanocyte dysplasia. Terms exist for these PREcancerous findings because they are, by definition NOT CANCER (otherwise, if they were cancer, we'd call them cervical cancer, colon cancer, and melanoma)...

Dysplastic lesions, not being cancer, often regress on their own or simply never evolve into cancer, staying in the "dysplastic" state until death. However, if they *do* become cancer, they do so through a process that is called "malignant transformation". Literally, something that is NOT malignant TRANSFORMS into something that is.

Why did the ABVX management team include this in the list of "malignancies"? Honestly, I don't know. I think it is an evident mistake, and a strong piece of evidence that they didn't think they'd actually have to explain away a "cancer signal" in this dataset because their analysis of the data told them that there isn't one. If they were worried that the market was going to interpret these data as a catastrophic malignancy risk (which, make no mistake, is what the current low $70s price tag is assuming), they would've likely adjudicated this more thoroughly and left the "malignancy" that is by definition NOT malignancy off of the "malignancy" table...

So that is tossed out easily IMO. 6 cases left now. 4 of those are NMSC (non-melanoma skin cancer). I gather that people are dramatically overestimating what a diagnosis of NMSC means. Far be it from me to minimize NMSC (since it is what I treat for a living as a dermatologist), but guys....this is NOT in the same category as ANY other malignancies. NMSC is a milder category of its own, and I don't mean that as a matter of opinion. Literally, "non-NMSC malignancies" is a distinct endpoint used to gauge risk of "serious" malignancies in clinical trials. NMSCs are left out of that category because they almost never are "serious" - certainly almost never life threatening.

Here's an exercise anyone can do to drive this point home. Google, or ask an LLM "what are the 10 most common cancers in the United States?". They are all going to give you the same answer: Breast & prostate will be the top 2 at slightly >300,000 cases/year.

So breast and prostate are the #1 and #2 most common cancers according to every source...except, those sources either ignore completely or footnote at the bottom that there is a type of cancer 15x more common...NMSC!!!

The point? Ubiquitously, NMSC isn't even included on the list of "most common cancers" because they're frankly in a separate category altogether from cancers like breast and prostate. It actually is controversial whether or not it is even possible for basal cell carcinoma to metastasize, and (aside from transplant patients), CSCC is almost never fatal unless left ignored/untreated for years (people ignoring a giant bleeding skin cancer is perhaps more common than you'd think, but not happening in any clinical trial patients).

These 4 50mg NMSC cases (vs 1 in the placebo group) are a not representative of serious malignancy risk even if the market is acting as if they are...they are absolutely in milder a category all their own, and lumping these all together is a mistake.

Again, if people think these 4 NMSC cases are some scary life threatening event, they're just flat out wrong. There are >15x more cases of NMSC than breast cancer in the US/year, yet >10x more breast cancer deaths occur in the US per year.

Again, not to minimize my own career too greatly, but almost *always* NMSC are removed by VERY simple, ~10 minute procedures under local anesthesia. Cutting out (or scraping away) the lesion typically takes me around 60 seconds, and the bulk of the procedure is actually spent stitching the patient back up. Drive yourself to the office, drive yourself home, local anesthesia, under an hour, you're cured. Hell, in many places in Europe it is actually standard practice to not even "treat" a basal cell carcinoma! On many body locations they are simply biopsied, and once diagnosed they are considered cured by the biopsy itself!

It has become very clear to me that people are thinking that these NMSC cases are highly relevant cases of severe, potentially fatal cancer. They simply are not. There are *millions* of these in the US per year and most are treated with <15 minute procedures. These are in a TOTALLY different, far less serious category of "cancer".

So again, why wasn't $ABVX prepared to discuss/explain this? I legitimately think they did not expect to need to. They may have overestimated the market's knowledge here and underestimated its potential for a knee-jerk reaction to the "C-Word". It's a mistake, yes, but it ultimately doesn't change the profile of the drug.

So, I think we have compelling cases to write off the colonic dysplasia (literally not cancer) and NMSC cases, as I have usually found to be standard in these situations.

That leaves the breast and prostate cancer cases. Again, the otherwise #1 and #2 most common cancer types...funny how that worked out! I sincerely do not believe that these two cases alone represent a signal against 0 in the placebo arm. This is textbook small sample statistical noise, ESPECIALLY for a drug with no mutagenic risk AND no immunosuppression (literally, HOW would this drug even be causing cancer then???).

However, clearly the market will want more info here on these two cases.

Hopefully the market will wake up to the points above (that $ABVX and I mistakenly thought were obvious) highlighting that the colonic dysplasia and NMSC cases can be almost completely written off. After that, hopefully $ABVX can give us more info on these two "legit" cancer cases (breast and prostate).

Yes, they should've been ready to do so on the call. they messed up, but let's see what the details show. Some are saying we will see updates sooner than the October conference like they initially guided for on the call (at which point they clearly did not expect the market to be freaking out at all).

After that, we also need to see the data from the 50mg "escape/placebo" arm that was not part of the primary efficacy analysis. That's is own topic of conversation, but that could significantly rewrite the narrative (now that $ABVX is aware a narrative needs to be rewritten after it got away from them).

I think the market thinks they are hiding these "escape/placebo" arm 50mg patients' data. I believe they were just totally caught off guard by the market's reaction to the "cancer signal" here and didn't think they'd need to have that dataset ready to prove there's no cancer risk (they thought the initial dataset spoke for itself...I agree, but so far the market clearly doesn't).

There should be several hundred patients worth of extra 50mg patients in that group. Ideally they can move up the release of that dataset to help qualm the market's fears and try to prove they aren't trying to hide anything there. Depending on the sample size there, we should very likely expect a few "cases" there too, but if the rate comes in lower than the original 50mg data we got, this narrative could snap back rapidly. Let's hope!

[Coen @CoenS26]

@AlexandrG1980 @seedy19tron 6.25%

[Coen @CoenS26]

@ParadisLabs What about margin?

[Coen @CoenS26]

@aleabitoreddit What would you make of @jasonschips ' comments?
(https://t.co/GECYr0JHCt)

[Jason's Chips @jasonschips]

https://t.co/qrvphjmNQF

[Coen @CoenS26]

@PhotonCap Likely just sell the news reaction before earnings tmrw

[BG Edgelord @BgEdgelord]

@aleabitoreddit SIVE Short sellers finding out the infinite losses part

[Paradis Labs @ParadisLabs]

If you didn't know...I'm very bullish on $IQE

$MTSI £45M investment materially cleans up the balance sheet + de-risks operations.

It allows them to repay debt + fund core capex. And allows them to drive capacity towards more photonics stuff.

As a standalone catalyst, that's huge for a company at a tiny MC of just £448M.

So they've got Macom as a customer now via LTAs, and $LITE as their flagship customer too.

And you've got huge institutions like Lombard Odier, Artisan, and $IBKR as significant shareholders.

I expected the $MTSI dilution to force the share price down to the low 30p level - which we hit last week.

So looks like dilution may have already happened if the new shares hit the register sooner than I thought initially.

Imo, the significantly de-risked business post-fundraise deserves a material re-rate to more premium valuations.

[Moody @MoodyWriter13]

Investing is like marriage.

Many people commit to both at the height of euphoria, when everything shines, expectations are high, and the future seems like a straight line upward. Even the German word for wedding, Hochzeit, literally implies a “high time” or peak.

But a peak is rarely a beginning. More often, it marks the moment from which reality slowly starts catching up with inflated expectations. Precisely because everything appears perfect in such moments, the potential for disappointment is greatest.

Wisdom suggests not committing when the magic feels strongest, but when you have soberly recognized that the foundation is solid, even without fireworks and illusion.

The same is true in investing.

Most people buy stocks when the story is already obvious to everyone, when expectations are at their highest and valuations leave little room for error. But buying at the peak often means paying not for what is, but for a perfection that can hardly be exceeded.

The better opportunities often emerge where sentiment is muted, doubts prevail, and much of the bad news is already priced in. When it becomes clear that the worst is likely behind, even modest improvement can turn skepticism into renewed confidence.

That is why I prefer investing in companies where I do not need everything to go perfectly, but where the odds are greater that the future will simply be better than the present.

True wisdom in investing is not about buying at the most beautiful moment, but about recognizing the turning point.

For example, I “married” Sivers when almost nobody knew it and almost nobody wanted it. And I “separated” when I began to fear it might become the next Bonnie Blue on social media. 😉
Just joking. It was only ever a trade from the very beginning and its future is still entirely uncertain.

Trading on the other hand is therefore more like short term dating or fucking around. Eventually, everyone has enough of it.

[Coen @CoenS26]

@PhotonBull @roundhill Is $sive going to be in it?

[Coen @CoenS26]

Got some abvx as well @MoodyWriter13 ?

[Coen @CoenS26]

@cryptogoos GS calls it Ramageddon because of the shortage, not because of the crush. Bs

[Coen @CoenS26]

@aggregategains @seedy19tron Yea im pretty sure its going to be a waste of my money when data lands, but better be safe..

[Coen @CoenS26]

@meremrtl @seedy19tron

[Coen @CoenS26]

What is this $VICR price? People moving to $CRBS? Anyways im picking some small bits up @joedab12

[pork @Taintslapp12283]

$ABVX I have heard of dropping the price to shake out retail. But have you heard of being bored out of a play?