Randall Ching

$CAPR wrote down my thoughts on the HOPE-3 data here. took both sides of the argument (PUL fragility vs. LVEF efficacy) docs.google.com/document/d/1qj…

@counter121212 @AppleHelix Well the problem with RGNX was not only the primary endpoint biomarker but the short length of the data and the poor methodology for classifying the attenuated population. Just reading the literature on heparan sulfate makes it clear that measuring an internal fragment is poor

@surferbackpack @AppleHelix No, $RGNX had FDA alignment on D2S6. More importantly, RGNX has HS data (not just D2S6) AND submitted it to the FDA. The RGNX outcome was Prasad being Prasad. DNLI was not decided by CBER and Prasad is on his way out. That explains the different outcome.

So CDER approved $DNLI’s hunter syndrome drug using heparan sulfate, the SAME biomarker that Vinay Prasad’s CBER rejected for $RGNX’s hunter syndrome GTx?

@AppleHelix Yeah maybe, I’m looking at their posters and presentations and it’s all D2S6 in their biomarker figures. RGNX also had a poor methodology for distinguishing the attenuated pop. of MPS-II patients and other problems (relatively short data) compared to other MPS competitors

So maybe the difference is type of HS. I can’t believe this would big have been aligned with FDA. Also regenix should have measured both.

@BrainyMarsupial @DavidCh34622985 @abracabrasian Yeah it’s a combination of the wait time, dilution, and the manufacturing risk can’t be understated. It’s hard to make and has history of manufacturing rigor. Think once they PR about their batch progress, it slowly moves upward

This is more my slightly optimistic base case, something like 15-30% dilution sooner or later. But I do wonder how much of the price is truly a reflection of dilution expectations? Seems like there is more to the story. Maybe just sidelining money until catalysts given the long wait

$sprb are we serious? flat to xbi? after a near guarantee of approval and the 200m that comes with it? if it is worth 68 today, it definitely wasnt worth 64 yesterday. thats all i know.

@AB1001_disciple @AppleHelix D2S6 is a fragment within HS that has very little published literature supporting its use as a method of quantifying HS. Measuring D2S6 is quite non-specific. Total HS makes more sense but still falls under HS-NRE that measures the HS terminal caps indicative of enzyme deficiency

@surferbackpack @AppleHelix can you expand on why the RGNX choice was an issue from your pov

@AppleHelix I’m pretty sure FDA never agreed that HS-D2S6 was an RLSE. Only accepted study design for BLA in principle. CRL and notes states D2S6 was not in line with standard clinical practice and no published literature supporting D2S6

@surferbackpack This would have been aligned with FDA. Also nothing previous another assay. Maybe amount of samples

@BrainyMarsupial @DavidCh34622985 @abracabrasian Mm I think that’s best-case for shareholders right and just CEO talk regarding non-dilutive/partnership. Best-case to use when trading it though, imo, is assuming dilution. Sort of shield yourself from oversizing and you capture the delta if a partnership/non-dilution does occur

@DavidCh34622985 @surferbackpack @abracabrasian Imo there won't be any dilution until post-filing, and they might not even need to dilute at all as they're looking for non-dilutive sources of funding. Current runway until early q1 per the recent fireside meetings.

@BrainyMarsupial @abracabrasian I think it’s just patience on Spruce. All of the assumptions we made so far regarding DNLI’s approval, satisfactory data, and the wait on cGMP are still in tact. From the trade strategy side, I just hold with an avg of 57 now.

@abracabrasian Retail doesn't appear to understand the implications of this or how similar the data package was between the two. Will be interesting to see @surferbackpack interpretation on how this impacts Spruce.

@realguenel Seriously. It’s mind boggling how some Peptide enthusiasts don’t understand the importance of an RCT, especially if the indication is a non-rare disease. The argument of legalization and net-harm reduction is cope. These guys would get killed investing in biotech.

@surferbackpack he's like a modern socrates now fighting against peptide extremists lmao

throwback to this classic. quantum compute bulls are the lowest iq market participants.

@Relic57647069 @StockSavvyShay Insanity 😂

@surferbackpack @StockSavvyShay bro got 5 bot replies instantly lmao

Jensen Huang says orbital data centers could tap continuous solar power in space and push compute to new limits. The challenge is cooling without air or conduction so $NVDA is exploring massive radiators along with redundancy and radiation hardening to make it viable.

THE GREAT PEPTIDE DEBATE: FULL DISCUSSION Peptide bear @MartinShkreli squared off against peptide bull @maxmarchione today in a back and forth on retatrutide, BPC-157, randomized controlled trials, the FDA, the pharmaceutical industry, and more. 00:00 Opening arguments 06:08 Martin on the downsides of retatrutide 10:24 Back and forth on BPC-157 14:41 Randomized controlled trials — issues and benefits 19:19 Max on the potential of Thymosin Alpha-1 23:21 Martin on why peptides should be controlled substances 26:07 The FDA's strengths and weaknesses 29:05 Closing arguments

@US_FDA @VPrasadMDMPH

Are you ready to shape the future of public health at the highest levels? The FDA is seeking an exceptional executive leader to serve as the Center Director for CBER—a role at the forefront of regulating life-saving biological products, vaccines, and emerging therapies. This is an opportunity to protect and advance public health on a national scale. You'll work on cutting-edge science, shape critical regulatory policy, and lead a team dedicated to ensuring the safety and effectiveness of biological products that save lives. Apply by April 3, 2026. #FDAJobs usajobs.gov/job/862056100?…

CRL’d. $ALDX Tanked a lot more than I expected. Nice!

@EJLIV850 Biologically impossible SDs yes. I treat the exercise as a conservative approximation/ sensitivity stress test where I test the drug against a variance bar harder than reality.

@EJLIV850 Clear limitation yes. My thought was if hedges G based on weighted pooled SD still lands in medium effect range after I’ve unsmoothed the MMRMs confidence, it gives me a tell the signal is not very fragile. Reversed SD is a proxy since I don’t have patient level data

$SPRB Back with a paper on the BSID Cognition Data from WORLD 2026. It's 8 pages (mostly tables) of statistical analysis and I'd very much appreciate any replies for further discussion. Thank you all for the continued learning :) docs.google.com/document/d/1Hz…

@realguenel ill send you something in DMs

@realguenel table 3 in my paper then used the approximate SDs to calcualte the weighted pooled SDs. the weighted pooled SD is the right denominator to compute Cohen's D which was then adjusted using Hedges g to penalize the small sample sizes.

1/ Hey @surferbackpack great work on the $SPRB BSID-III cognition analysis. Genuinely one of the better independent breakdowns I've seen on this name.