Ipollit

Long: $CRVS, $TGTX, $PTGX, $ARWR, $SRRK, $OVID, $TNGX, $XENE, $MGNX, $KYMR, $AML, $NRIX, $OCUL, $VKTX, $SNDX, $KNSA, $CLDX, $IDYA, $WVE, $LRMR, $JSPR, $PRQR, $BCYC Watch: $BEAM, $CCCC, $IKT, $KRRO, $KURA, $PALI, $STRO, $VSTM, $ZYME

@ezmoneymonty @A_May_MD @nolastevedore What do you mean? In trials? There is a strict exclusion criterion reg the risk of TB or other latent inf. TB mon applies to all IBD drugs, even IL-23. For the latter, the req is now being relaxed. In the future, Obe could eventually be relaxed as well. init as new MOA stricter

@ipollit77 @A_May_MD @nolastevedore How many TB cases were there?

🚨$ABVX just quietly dropped new slides again! Aside from showing a much better/clearer discussion of data/expectations and a clear goal to handhold the market with the upcoming part 2 dataset, these slides give us another key insight: $ABVX is finding the same expected background nNMSC/NMSC rates as @deathtouch2k and I have discussed. nNMSC/100PY expected range: 0.3-0.7 ↪️Obe's rate so far: ~0.59 NMSC/100PY expected range: 0.7-1.4 ↪️Obe's rate so far: ~0.79 And those are just for the 50mg doses...the Obe rates get further diluted massively if you were to include the 25mg dose levels, suggesting that the overall population is likely on the low end of expected cancer incidence. (Note the the calculations can change slightly once we get exact numbers of PY of exposure). So, even just looking at the 50mg dosing patient years, and not including the Part 2 data that might further reinforce safety, $ABVX is getting the word out that their EXISTING cancer event rates are ALREADY well within EXPECTATIONS...the market is clearly waiting for the Part 2 data before coming to this conclusion...but I personally don't see why we need to wait. These data are very clear. I continue to see no evidence of a "cancer signal" here, and I find the double digit stock price to be an absolute STEAL. $ABVX would very likely (IMO) have at least temporarily cracked $200/share on their absolutely unprecedented maintenance update without this (bogus?) "cancer scare". Those of us in the weeds have been able to see that the "cancer scare" was noise from the beginning...the company of course will be slower in reaching the market to get that word out and make people understand it, but IMO that's where we are heading. I would predict that stock price will follow!

@A_May_MD @nolastevedore Actually, I think there’s something fascinatingly ingenious about the MOA of obe. And I can still see myself going long on it. I’m trying to underst the risks (and pot upside). I had originally assumed you’d be able to dispel my concerns right away.Are these qs really irrelevant?

@ipollit77 @nolastevedore Hahaha ok now you’re trolling

@A_May_MD @nolastevedore $ABVX Obefazimod will likely require stricter TB monitoring in IBD patients. Icotyde probably not. Also interesting: As I understand it, tuberculosis bacteria protect themselves from immune cells in the lungs by upregulating miR-124. TB knows how to do it, too

@A_May_MD @nolastevedore Interesting… $ABVX lists pregnancy as an adverse event (as usual). miR-124 plays a role in embryonic development, particularly that of the brain. Icotyde, as an IL-23 inhibitor, is considered less risky. Does this have implications for young women?

@A_May_MD @RNAiAnalyst Are you suggesting that Ames tests or a carcinogenicity study in rats are sufficient to determine the cancer risk of a substance like obefazimod? Obefazimod is clearly not mutagenic based on the MOA

@ipollit77 @RNAiAnalyst You don't have to understand the MoA to read the results of an Ames test or rat carcinogenicity study................................................................... Are you equating all preclinical work to just figuring out the MoA??? LOL

$abvx would you rather be diagnosed with basal cell carcinoma or moderate ulcerative colitis?

@A_May_MD @RNAiAnalyst It doesn't make sense for you to talk about biological plausibility while at the same time praising the lack of clarity regarding the MOA

biologic plausibility doesn't care what probability you project.

@JackMan724444 $ABVX has enough upside potential that I wouldn't dare to short it

@ipollit77 My condolences on your short position

Here we go. The strength of $ABVX lies in the uncertainty of Obefazimod's MOA! Nice. Or maybe not?

@A_May_MD @RNAiAnalyst We had already agreed that the risk of cancer cannot be determined based on small studies lasting 1–2 years. The fact that cases are clustering at the 50 mg dose is noteworthy. From a purely statistical standpoint, I believe the prob of this being pure chance is less than 2%.

Yep. This is a point I've made as well - ALL the preclinical data/PK/PD characterization studies are in Obe's FAVOR. There is no biologically plausible discrete explanation of HOW the drug would be causing cancer. In that context, to say that the MoA is unclear is a WEAKNESS doesn't add up...all the preclinical data suggest what we know about the drug points AWAY from a cancer risk 👍

@RNAiAnalyst @A_May_MD miR-124 is a tumor suppressor. However, obefazimod does not simply produce miR-124. It merely makes splicing more efficient. The change in the tumor itself does not have a sufficient effect. Obefazimod is a modulator in active immune cells, not an anticancer drug!

@A_May_MD @ipollit77 When you have a nonstat sig 'signal', MOA and plausibility matter. MiR124 being well caharacterized to be tumor suppressor therefore will matter to FDA.

@A_May_MD @RNAiAnalyst So you're saying the FDA will evaluate these cases completely independently of the MOA? If there's a theoretical link to the AEs in the MOA, I think they carry more weight than if they don't fit the MOA. That's my opinion

@ipollit77 @RNAiAnalyst You evaluate the AEs by evaluating the AEs.

@CellSyde @RNAiAnalyst BCC, SCC, and UC are not cancer, no question about it. In the case of obefazimod, I don’t even consider them a good surrogate for cancer risk at this point

@ipollit77 @RNAiAnalyst Tell me you don’t know what basal cell carcinoma is, without telling me you don’t know what basal cell carcinoma is 🤡

@A_May_MD @RNAiAnalyst Sure, neither of those is cancer. But what kind of qs are these? I get the impression you guys have absolutely no idea about the MOA. You even said it was an advantage that the MOA is so unclear to you, bc then no comp could copy it. How are you supposed to evaluate AEs then?

@ipollit77 @RNAiAnalyst Buddy, you have zero idea what you’re talking about. ZERO.

@RNAiAnalyst Regarding cancer: At this point, I do not believe that obe has either a pos or neg effect on cancer due to its MOA. As I understand, the amount of miR-124 induced in the tumor itself is too low to have any effect. The effect on TME is less clear, but it appears to be protective

@ipollit77 It induces a microRNA that has been ascribed a tumor SUPPRESSING function...

$abvx given the 1) clean safety profile, 2) very high maintenance rates AND 3) novel and therefore likely complementary MOA... ...why not consider obefazimod in combination with other agents such as corticosteroids or Jak inhibitors for induction, but then obe monoRx for maintenance? Higher induction rates would also mean higher overall utilization (and profits $$$) for maintenance.

@RNAiAnalyst Right. My q about cancer was off the mark. I want to underst the MOA. Is it correct that obe enhances the splicing of non-coding precursor mRNA for miR-124-1 in the CBC? It doesn’t induce an arbitrary amount of miR-124 itself, but rather max the avail amount of this prec mRNA?

@RNAiAnalyst $ABVX Or to put it another way: as far as I understand the MOA, it shouldn’t be limited to IBD, but should have much broader potential… MS, RA, asthma. Am I misunderstanding the MOA? Does obe have little systemic effect and act mainly in the gut? Is this a pharmacokinetic issue?

@RNAiAnalyst Do you have a deeper understanding of the MOA? Could there theoretically be long-term (10+ years) risks related to cancer or the central nervous system due to the MOA, or is the MOA theoretically safe enough?

@A_May_MD @Msp194 @shirefindsvalue Any words on fezolinetant, which, due to comparable (unrelated) cancer cases in P3 and a similarly novel, unestablished MOA, is only used in a secondary role in clinical practice?

@ipollit77 @Msp194 @shirefindsvalue The single most successful drug in the history of IBD has a warnings and precautions note for cancer risk (Entyvio) $ABVX

$ABVX seems to have (in the last hour or so?) quietly released a new corporate deck with 3 important slides at the end. All, in my opinion, providing strong new information showing that these cancer cases were unrelated to drug and equivalent to expected background noise. Most important is the slide on the 2 non-nonmelanoma skin cancers. BOTH of these were more indolent, low/intermediate subtypes of their respective cancer (prostate and breast). Not only does this mean that the cancers are less threatening, it also means that THEY ARE SLOWER GROWING CANCERS. Why is this particularly important? Because it means that the development of the cancers very (very) likely PREDATES THEIR ENROLLMENT IN THE TRIAL. Look into the doubling times of grade 2 (Gleason 7) prostate cancer and grade 2 NST breast carcinoma. These are slow-growing tumors that very likely existed before these patients ever even had a dose of obefazimod. That relates to another key finding on this slide - the prostate cancer case was identified via PSA screening at 8.5 months into the study (remember earlier is better). In the Guggenheim conference they had said it was confirmed at day 367...they must have been referring to the biopsy confirmation of the subtype, not PSA confirmation of the prostate cancer diagnosis. This new information speaks to an earlier diagnosis. The breast cancer patient was diagnosed even earlier than that! Only 6.8 months of Obe exposure. Also, these new slides give us actual information on the prior drug exposures - before this afternoon we knew that they were on some prior treatments, but we didn't know what...THE PROSTATE CANCER WAS PREVIOUSLY EXPOSED TO ***5*** DRUGS WITH LABELED CANCER WARNINGS BEFORE ENROLLING IN THE STUDY! 3 OF THEM HAD ***BLACK BOX WARNINGS*** FOR CANCER RISK! -Humira (black box) -Infliximab (black box) -Rinvoq (black box) -Entyvio (warnings and precautions) -Stelara (warnings and precautions) We also just got new info on the NMSC cases (which matter far less but which spooked the market anyway). How you can look at the details of these skin cancer cases and think they are related to the drug is beyond me (but then again, these details just got released - quietly, for some reason). First of all, ***ALL OF THE 4 50MG CASES OF NMSC OCCURED IN 6 MONTHS OR LESS!!! Again, too rapid to be reasonably assumed drug-related. The fact that they all happened in the first half of this study is actually extremely exculpating evidence for $ABVX. Other details: -4/5 were 60+ years old (STRONGLY associated with skin cancer risk) -3/5 had PRIOR SKIN CANCER ALREADY(!!!!!) -4/5 had prior exposure to other drugs that are known to increase skin cancer risk. Finally, they also added a slide discussing that some studies have shown the elevated risks of these cancers for UC patients at baseline. -~5x higher risk of prostate cancer in IBD patients -~2x higher risk of breast cancer in IBD patients Why did $ABVX add these 3 slides to the corporate deck randomly, silently, on a Friday afternoon? IDK. Legitimately good news in those slides! I'd have pressed released this info as soon as I had it, because the details really help alleviate the (already statistically misguided) concern that these cancers could've been caused by Obefazimod. Here's the link: ir.abivax.com/static-files/e…

@Msp194 @A_May_MD @shirefindsvalue $ABVX Okay, fezolinetant is a good point. fez MOA primarily affects CNS. In contrast, obe targets the immune sys + tumor suppressor. The fez case makes it even more complicated: the cancer cases appear to have serious impl for clinical practice even w/o BB. Can you verify that?

@ipollit77 @A_May_MD @shirefindsvalue “Another safety consideration was an imbalance in malignancies in the fezolinetant treatment groups compared to placebo. This finding did not appear to be clinically relevant as many of the cases of malignancy appeared to be pre-existing, there was a short time to onset to the...