Navigating life with terminal disabled son. FDA/World Regulatory Affairs. Stock posts ≠ financial advice. Regulatory posts ≠ endorsement of FDA’s actions.
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Joined February 2025
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Came across this full Obe Phase 2 maintenance study data that I had missed earlier until hound shared with me few days ago. Couldn’t find Abivax publishing this level of details in any previous PRs.
- Endoscopic remission (ER) of 37.9 % in responders gives me assurance that bias in clinical remission (CR) 66.1% might be minimal. That is because patient bias is not possible in endoscopic healing and symptoms improve faster than complete bowel healing. It is established standard that CR trends ~ double of ER in UC maintenance trials. I would be worried if ER was worse like around 15%. Also, one component of CR is endoscopic subscore assessment which helps with accuracy of overall CR reporting and reduce symptom bias.
- ER can be influenced by Corticosteroids (CS) but Abivax did voluntary CS-free assessment and CR and ER in those patients were 37.4% and 23.5% respectively. Importantly this was done per FDA standard of min 12-week steroid free before assessment. 21 patients achieved CR from those who didn’t voluntarily taper CS. Results in CS patients were of the same proportion as overall study population. CS-free efficacy would have been even higher if there was forced tapering like required in phase 3 maintenance.
- Durability might help placebo a little so it will help the drug arm. Induction results in phase 3 are better than phase 2.
Overall, if pattern and math from phase 2 OLM holds in phase 3, high probability we see ~ 55% CR in 50mg arm with Placebo around 17-20% and delta ~ 35-38%. IMO.
pmc.ncbi.nlm.nih.gov/article…
Multi billion$ AI regulatory idea for whoever can come with AI solution:
Drug approval process was paper based 25+ years ago. Then it became electronic eCTD and adopted ICH M4QR1, an old submission format that is globally recognized in most markets.
FDA and other agencies have now R2 version 2 which is significantly different than version 1 and is expected to go live after 2027. This means 1000+ old submissions of each drugs and new drug submissions will need to comply with this new template requirements.
An AI tool that converts old format submissions into new format will be a blockbuster idea. Compliance issue so easy to sell to BP. Every pharma regardless of where they are located will need to adopt to this new requirement in couple of years. This is the kind of biotech thing @AnthropicAI should be helping with.
CAPR stands no chance from regulatory stand point. But, many others in last 6 months didn’t as well and still got approvals. “We are ready to accept uncertainty of data because of unmet need”. The best way to negotiate with someone is by spending half your time reminding them of how they recently negotiated with others. No position.
Marc didn’t sell in summer cause he wanted us to learn hard lessons first so we don’t loose all gains by year end. He will now sell in Dec and make our year. Truly a biotech hero! 😉
FDA will continue to be flexible like this next 2 years. After that if gov changes, it goes back to being rationally flexible like pre 2025. If FDA leadership changes, new compliance policies for AI bios will likely come. Not to stop them from what they are doing but to bring them close to same expectations as routine bios. ~2029 might also see first AI bio phase 1. Price pressure is common issue regardless of gov. Overall, next 5 year should be good for bio, shouldn’t it?
RVMD - Best in disease efficacy drugs in life threatening or serious diseases don’t need marketing. Patients and families come running asking for it. It’s 2026.
$PALI
Abbvie got their own gut targeted EP4 agonist. Pali is gut targeted by different mechanism, PDE4 inhibition. Both designed to minimize systematic absorption. Oral IBD space heating up.
AbbVie is paying $100M upfront for Nxera's gut-targeting IBD program, adding to a portfolio anchored by Skyrizi and Rinvoq. endpoints.news/abbvie-bets-u…
I have overseen and often led many new ideas through development and approvals. Often, also being one of the first one in the industry to face the FDA and EMA for novel things and participating while things are under construction. Below is how I think FDA and other agencies will regulate AI usage in drug development. It depends on the AI usage and its direct link to the patient safety. As I have been saying AI usage is a puzzle. Balanced use is important. The more you use more the regulatory complexity and more the cost, delay and maintenance. So where do we draw the line in first phase?
AI conversations have been all over the place in all directions and nobody knows where they are going. Everyone wants to do everything right now today only. I think time has come @AnthropicAI takes a pause & decide which direction they want to take and build in that direction. Because, drug development is one path where there are no U-Turns on the road. @Prof_Oak_ @nc_frey @eric_kabrams @LifeSciVC
Disclaimer - these are my views only and I’m not affiliated with FDA or any other health agency.
Claude/AI use up to some extent only is productive. After that it becomes the headache itself and adds cost, resources and delays than even current development timeline:
1) AI use for discovery, overall administrative, documentation, and scenario analysis with final decision still made by human ——— No or minimal regulatory implication
2) Decisions for nonclinical, CMC parameters, analytical studies, trial design, patient selection, diagnosis, dosage, administration made by AI/Claude ————— It’s a digital or software as medical device at this point. Every decision made by Claude needs to be validated using 10000 other variables which will need to be supported by the 1000 actual studies done by humans. Claude will be classified as medical device which will need to be registered and managed separately in addition to drugs or biologics.
This is how FDA will most likely think.
It's Halloween. Here's a trick-or-treat "thought experiment" for Anthropic (or OpenAI) going big into the Life Sciences. Probably more trick, than treat, but here goes...
Both have made making medicines a top priority, as described in Anthropic's S1. Right now they are taking some “small” bets in the space (~0.1% of expected market cap's). These are welcome moves and we are hopeful for more engagement in #biotech in general from the frontier lab companies.
But if you are a $2T public company (as they are likely to be post-IPO), how could you achieve scale in this life science domain? What’s the best way for maximum impact on bringing drugs to patients? [assuming that's the goal for their efforts in the life science]
I’d argue it's buying a large Pharma company and then radically changing the operating model to put compute and integration in the center.
Sort of like retrofitting a big Pharma R&D enterprise into a @NimbusTx model on steroids with compute and tech integration in the center, intercolated with deep biology and drug hunting capabilities, with operational execution on the periphery (impt, but not the driver). Own the learning loops, compress the DMTA cycle across a huge portfolio. Nucleate and empower teams around great potential medicines in a decentralized R&D model...
Let me get vaguely specific, for illustrative purposes.
Anthropic could buy $BMY for less than 10% of its market cap, an all-stock deal.
BMS has about 30,000 people. Trim commercial (a distraction to the radical change mission) by selling the long list of tail products (top 5 products are 70% of revenues).
Then apply frontier AI models to the business across the board - commercial, manufacturing, and R&D. Tons of data sits in these silos. With data, figure out where the bloat is in the corporate bureaucracy and remove it. Be especially aggressive on scaling back G&A and the lawyers, replacing headcount in those functions with AI-enablement. In the business functions, allow change-makers to focus on operational efficiency.
In R&D, BMS has about 3000 scientists/clinicians and operators on their R&D team. Keep or even grow this group - its where the magic has to start.
BMS has a legacy of great R&D advances and has tons of historical data. Frankly, they probably have some of the deepest datasets on mAb discovery (Mederex mouse one of the most prolific mAb platforms ever), induced proximity (CelMod and related datasets are without peer), cell therapy (Juno was a pioneer with one of largest CART datasets), radiopharma (more recently), and so much more. Deeply mine these datasets.
Take all the "me-too" R&D spend on crowded targets and dial it out of the portfolio... Refocus all that energy on building deep biology datasets to complement the historical modality data. Invest in deep cell and tissue profiling, all the ‘omics, at scale and in an integrated way. Put AI into the center of the operational workflow as an enabling tool for drug hunters, not replacing them. Work on fewer projects as a whole, but focus on “holy grail” drug targets and first-in-class/first-in-modality programs aiming for step-changes in treatment. And let AI operational efficiency compress clinical timelines as much as possible (10-20%).
Unleash teams of drug hunters with AI-powered R&D at scale on any/all therapeutic areas, not restricted to where commercial wants you to focus. A true science-first enterprise at scale. “A great medicine makes a commercial franchise, a commercial franchise doesn’t make great medicines” rings true to me here. Commercial voices, I'm told, dominate at BMS, even back in R&D. Maybe that's not optimal?
This would be a radical overhaul of a large R&D-intensive company. Give the experiment 5-7 years to alter the vector of R&D output. Long enough to see discovery-led changes percolate into early development and clinical PoC...
This kind of ongoing R&D investment would be tiny fraction of Anthropic’s revenues during that period, offset in part by the profits from the big commercial brands. A rounding error for them, but if it worked, this would fundamentally alter the industry’s trajectory.
Probably can’t be done - changing large legacy groups is hard - but seems like the only near-term way to truly test “AI at scale in drug R&D” is thru something audacious like this, rather than just thru small (and beautiful) case studies of program-focused biotech …
With $5T+ of anticipated market cap between the handful of frontier lab companies, this seems like a relatively small bet on a big prize.
And, lastly, make @Prof_Oak_ head of the BMS business unit of $ANT.
Trick or treat? Boo!!
BMS is a technologically backward company. You need to partner or acquire companies that have current marketed drugs with digital and software platforms helping with diagnosis and treatments. These products are called Drug-Device combination products. Genentech where @nc_frey comes from is best choice. Other great options are J&J, Merck, Tak. Pfizer is backward as well.
Bio specialist funds who wrote letter to WH last year asking FDA to be easy and flexible will have to write another letter in near future requesting it to be disciplined when AI bros start submitting their N=5 molecules without being in any compliance nor meeting any requirements.
A rule and guideline based disciplined FDA is in interest of patients, sponsors and investors!
$Pali
Management has been slow but next 12 months will be execution by CRO and reputed IBD recruitment agency they have partnered with.
This won’t be close to obefazimod in maintenance. Period! Management is targeting 20% CR delta in induction which aligns with Icotyde and prior apremilast 30mg data. I think this can be decent drug with antifibrotic profile in any market left (😉) by Obe. Marc has been boasting about Obe antifibrotic profile and someone might see that value in Pali too.
Gut activation and slow systemic release will further improve data. If anyone has analyzed PK profile, please share your view.
Also, someone ask Dean Li $MRK tomorrow when he is releasing Tuli data. Second half is almost over and no conferences left this year which he mentioned in calls.
Palisade Bio Announces First Patient Dosed in Global Phase 2b ASCENTRA-UC Study Evaluating Once-Daily Oral PALI-2108 for the Treatment of Ulcerative Colitis
bit.ly/4dXWZfC
$PALI #UlcerativeColitis #Crohnsdisease #IBD #GIHealth
The bear argument I have read so far is that 2 of their patients had endoscopic & histology baseline of 0 when mMS was higher. How is it possible? Well it happens due to several reasons but it’s normal. Patchy disease, severe disease history so bowel is narrow or IBS or so stool frequency is higher and therefore mMS is higher but histology looks clean. KOL are goin with this data in all conferences. I guess they are not stupid to not see it. pubmed.ncbi.nlm.nih.gov/2759…
