Chaotropy

Just published my new article “Monte Carlo Simulation Of @ElicioTx's Phase II AMPLIFY-7P Study Favors Vaccine Efficacy” (free link in comments). $ELTX I built a Monte Carlo simulation to model the delayed and ongoing AMPLIFY-7P trial using informed estimates and incorporating all publicly available information. Looking forward to your feedback!

@SnupSnus Thank you! :-)

@chaotropy Have a follow for building and posting this! (I don't know the tenax story so can't comment on that sadly)

Perhaps the most striking result from my PK simulation of $TENX's oral levosimendan (TNX-103): at modeled steady state, the lowest point in the oral dosing cycle may never drop below the IV peak. Throughout the entire final dosing week, the model suggests oral TID could maintain free effective concentrations above the IV weekly maximum. Looking forward to your feedback, especially from @A_May_MD!

Thank you so much for reading and for this feedback, I really appreciate it! :-) I chose not to calibrate against the transition data by Thenappan because those patients had 18+ months of weekly IV before switching to oral, so the values do not cleanly reflect a single regimen in isolation. With N=18 and roughly a 10-fold spread in individual concentrations, it’s also difficult to extract a reliable number to build against. My model was deliberately conservative and anchored to published conversion rates. In hindsight I probably should have discussed the transition data reported by Thenappan more explicitly in the article rather than just citing it in passing. Since it validated rather than challenged my model, I treated it as confirmatory and moved on rather than discussing it in depth. That said, I think the patent data is broadly supportive. Measured levels appear to be higher than what my model predicts, which if anything suggests my estimates represent a floor rather than a ceiling.

@chaotropy Did you already look at the IV to oral PK study? They measured people who switched from IV to oral. How does that stack up with your model?

Just published my new article “Pharmacokinetic Simulation Of Tenax's Oral Levosimendan Suggests Higher Drug Exposure Than IV Dosing In PH-HFpEF” (free link in comments). $TENX Looking forward to your feedback!

@Leooweb3 Biotech.

Gold is crashing. Silver is crashing. Crypto is crashing. Stocks are crashing. The dollar is crashing. Real talk what should we buy now?

@growthrapidly When my conviction is really high, I force myself to buy more than I want. That way, I can trim and still hold the position I initially planned to hold. Risky approach to trick yourself. Don’t do this.

@chaotropy True. If I stayed long enough in $RKLB, I would have 10x my position easily. But I trimmed a lot after 4x, and eventually sold the entire position. Big mistake.

How hard is it to hold a 10x stock all the way without trimming?🤔 Be honest.

@growthrapidly Wasn‘t hard with $VRNA and $RKLB

@chaotropy That's true!

@slavov_n Thank you, great read! I started a series of articles about the origin of life / RNA-world hypothesis in late 2023 (free link below)… open.substack.com/pub/chaotropy/…

A periodic reminder to leave behind simplistic & naive notions.

Over the past few weeks, I built a PK simulation for a drug in a late-stage clinical trial. There is currently no approved treatment for the targeted condition, and a PK model could offer valuable insight in this particular case. I'm now writing up an article and hope to share it with you this Sunday.

@MartinShkreli Thank you! $LLY brought the first peptide (insulin) to market in 1923. 1923! That was over a century ago. Peptides as medicines are nothing new. This idiotic peptide hype needs to stop. There are so many genuinely exciting things happening in biotech, but this isn't one of them.

Just published my new article “Two Delayed Cancer Vaccine Readouts: Why I Am More Optimistic About AMPLIFY-7P Than REGAL” (free link in comments). $ELTX $SLS

Australian data scientist Paul Conyngham used ChatGPT and AlphaFold to design a personalized mRNA vaccine for his dog’s cancer. One tumor shrank 75%. Amazing story. But mast cell tumors are masses of granule-packed cells full of histamine and cytokines that swell and deflate with degranulation. A tumor looking 75% smaller might just mean inflammation resolved. Did the dog get corticosteroids, which are very common in treating dogs with malignancies? The dog also had chemo and surgery before the vaccine. Both kill tumor cells and might lead to the release of antigens, which can prime T cell responses weeks to months later. No control group, so no way to know what actually caused the shrinkage. And the leap to humans is non-trivial. Individual dog breeds have narrow MHC repertoires because of selective breeding bottlenecks. Humans have vastly more HLA diversity. Pick the wrong neoantigen in a human and you don’t get a useful T cell response. The hard problem is efficacy across diverse immune backgrounds. Worth noting that a second tumor on the same dog did not respond at all. The actually interesting part is the speed of Conyngham’s pipeline. Sequencing to manufactured mRNA vaccine in two months using publicly available tools. Undoubtedly inspiring and great work!

"In 2025, Elicio continued advancement of the randomized Phase 2 AMPLIFY-7P trial in post-resection mKRAS PDAC, with the event-driven primary DFS analysis remaining on track for an anticipated 1H 2026 readout" $ELTX

In 2026 it feels like the case for KRAS inhibitors in PDAC strengthens every week. A study published yesterday in Science (Than et al.) found that giving RAS(ON) inhibitors (RMC-9945, G12D-selective, and RMC-7977, multiselective, both from $RVMD) to mice with precancerous pancreatic lesions, before any tumor formed, caused those lesions to regress. Median survival went from under 5 months to over a year. The more interesting finding: interception outperformed treatment of established tumors with the same drugs. $BBOT $VSTM