$VKTX - There was only 1 (as in ONE) discontinuation due to an AE in the induction phase of the Maintenance trial per the PR*. ONE, in an accelerated 2-week induction titration scheme‼ (I'm not talking about total DCs in induction, only the ones due to AEs.) For those of you good at math one out of ~161 treated in induction is less than 1%. Discontinuations for other reasons (e.g., withdrew consent, lost to follow-up, protocol deviation) aren't reported, but the n's suggest they happened. There were 161 VK2735 subjects in the induction efficacy population and only 143 appear in the maintenance arms, so roughly 18 appear to have left during induction (I did the math). ➡I will repeat for clarity that only 1 (one) discontinued due to an adverse event out of 161 treated in induction. That is less than 1%. (@ChillBanking please feel free to comment😉) ➡This was in what many thought was a really aggressive titration scheme that would be problematic (not me, and certainly not Viking). ➡On GI AEs during induction, the PR says they were "characterized as mild" and that the incidence "was low and declined over time." Despite "the accelerated 2-week titration schedule," rates were "similar to those reported in the prior Phase 2 study" (VENTURE), "which utilized 3-week titration steps." *Note: Here is the direct quote from the press release I refer to: "One subject (1%) in the induction period discontinued VK2735 treatment due to an adverse event."

RT @ACInvestorBlog: $VKTX I don’t get the pile-on over this offering. The deal launched at $400M and came out upsized to $500M, with Morga…

$VKTX My July thread aged well — VK2735’s maintenance data reinforces how much cleaner its safety profile is versus retatrutide.

The market still isn't pricing $VKTX correctly, but that's fine. This trial was a major de-risking event

$VKTX reminder $VKTX & it’s obesity platform - most likely the reason it’s still independent as it’s so hard to value it 🤷‍♂️

$VKTX Upcoming major catalysts in next 9 months : ➡️Phase 3 Oral VK2735 start ➡️"Obesity Week"-> Detailed data on Maintenance Study ➡️VK3019 Viking's Amylin compound reporting on ph1 (SAD data could come before EOY) ➡️ Oral Maintenance study. Should include a QW dosing option and this remains the first ever dual agonist Oral in development. ➡️VANQUISH-1 ph3 Top line data (study should complete May 2027) Don't sleep on the Oral. The Amylin has great potential. VANQUISH-1 Phase 3 reporting is not that far away and the most important data set for Viking.

$VKTX Maintenance results out today were exceptional and a real best case IMO. I will have a lot more to say later but here are a few choice comments: ➡️WL is BIC. VK2735 is better than RETA at same point in time. It's just better with far fewer side effects. ➡️Monthly (QM) dosing works in maintenance ➡️Every other Week (QOW) dosing works in maintenance. ➡️No evidence of Plateau out to 33 weeks. ➡️Tolerability is great even at accelerated dosing and we have some YADOs (Yet Another Dose Option). ➡️We now have data beyond 13 weeks,. We have data to 21 weeks in a very high powered pool arm that should remove a lot of risk for Big Pharma to make a move before EOY 😊😊😊This was simply a home run IMO. 😊😊😊

JUST LIKE THAT!! A cross-border completion from @FitzMagic_14 ➡️ @StevieJohnson13

$VKTX interesting comment from Seedhouse “Specifically this trial is testing new peak doses, novel titration schema, indeed various maintenance regimens, and in our view will report weight loss numbers that look favorable vs. retatrutide (not tirzepatide, retatrutide).👊

$GPCR $PFE $VKTX $NVO $lly Can one lose 3% of their body weight due to vomiting alone? $MTSR showed up to 5.3% weight loss by Day 8 with its amylin. We’ll need to see the MAD data, but so far, these results don’t look encouraging to me at all

$GPCR In the 45 to 180 mg aleniglipron arm patients spent 16 weeks on 120 mg with essentially flat weight loss. After escalating to 180 mg at week 64, they actually gained weight (!!!) through week 72, despite being on the highest dose. What happened there? The 120 to 180 mg arm also appears to gain weight between weeks 52 and 60. Clearly no signs of a plateau, you guys. I really like how they reported AEs only for the weeks 36–72, while conveniently leaving out the first 36 weeks

MS notes "we believe some investors may be focused on the 17.5mg weekly arm through the full 33 weeks to gauge the longer-term weight loss profile". ⚠️⚠️⚠️⚠️A warning on this⚠️⚠️⚠️⚠️: ➡️N=15 in this arm, and it's the same 15 people who are inside the N=120 pooled induction cohort. They're measured precisely at week 21, then become a small subgroup for the next 12 weeks. A couple of discontinuations- and whatever assumption gets made about where those people ended up- can bend the curve on its own. ➡️A plateau at N=15 may not be a real plateau. My rough math- roughly about ±4 percentage points on the mean at 95%, so a −22% print is really "somewhere between −18% and −26%."‼️Did I say N=15 enough here? ➡️This arm stays on 17.5mg the whole 33 weeks- the dose doesn't drop. But 12 of those weeks sit inside a "maintenance phase" where most other participants are being stepped down or placebo'd. I think that biases the whole period toward maintaining rather than continued aggressive WL. That's my hypothesis, not a known. Just be aware this data may be poorly received and wrongly interpreted. ➡️This cohort also sits after 21 weeks of induction, where WL curves tend to flatten anyway. The stock may react negatively to this arm and violently(don't shoot the messenger). Modeling says continued WL, not a plateau- but N=15 is noisy enough that a flat-looking curve could be sampling. It could also print great. Either way it's 15 people, healthy adults on a compressed titration in a PH1, not a VANQUISH preview. 👉👉👉The much more important number is WL% at week 21, where N=120.👈👈👈

$VKTX - @bioinvestor24 makes excellent points in the quoted post. 🙏 I agree with all of them, and want to add detail on one: ➡️ The +5 mg step at Week 10 in #VK2735 VENTURE (10 → 15 mg) did not produce an outsized AE signal. The Week 1 spike in that arm came from a 5 mg opening dose in drug-naive patients. This is the only arm that started there. The other arms opened at 2.5 mg. ➡️ 15 mg arm, Week 1: 27 GI events, nausea in 17 of 35 (48.6%). Week 10: 4 GI events total - nausea 3 (8.6%), vomiting 1, no diarrhea, no constipation. A real uptick, but not a Week 1 repeat and gone by Week 11. ➡️ This isn't unique to a step-up week. The 5 mg arm logged 12 GI events in Week 4; 5 mg Week 2 and 10 mg Week 4 logged 6 each. ➡️Small scattered clusters show up throughout the study. Caveats: n=35 per arm, so one patient moves a rate ~3 points, and by Week 10 that arm is already tolerized. Here are some slides including a modified one from my original article (green = the nuance). Take a look for yourself:

$PTGX Jefferies BUY PT$171 caught up with MGT Mimrylo label bodes well for rapid commercial adoption, supported by broad indication, 1st fatigue claim with Ph3 RCT data, clean safety, and SoC like monitoring. ~78% of treated PV pts are inadequately controlled, creating large opp'y. $TAK $1-2B peak sales forecast predated strong Ph3 data and favorable label, suggesting conservatism. With two sig royalty streams, PTGX is well-funded for multiple high value oral peptide pipeline.

$PTGX is on a roll‼️ Just got approval for another partnered peptide drug. MIMRYLO (aka rusfertide) was approved Aug 28. They got a best-case "broad and clean label" according to JPMorgan. ➡️As a result, Protagonist got another big milestone payment ($275M) and will receive double-digit pure profit royalties on this second drug with blockbuster potential (ICYMI - ICOTYDE was the first).

$VKTX - The GI profile in the induction phase matters even though it is not the same as the titration in Vanquish. If it is good (as in consistent with the class and equal/better than say Tirzepatide's) then VK2735 will have another way to dose -> 2-week titration blocks rather than 4. Yes, this would be "off-label" but there is a lot of that happening now with both approved and compounded GLP1s varieties. Consider also: ➡️There is a segment of the market that will want to lose weight fast and would possibly risk the AE profile to do it. Getting to the top dose of 17.5mg in 12 weeks (the time it takes in induction) rather than 26 weeks would also save them money as an incentive. ➡️This would be a material competitive advantage over Tirzepatide should this 12-week titration prove viable. (Tirzepatide takes 20 weeks to get to its top dose of 15mg) ➡️ Being able to titrate up quickly says something about VK2735 tolerability that reads through to the Ph3 Vanquish study in a positive predictive way. VK2735's TMax at 70-90h is later/longer than key other GLP1's (E.g. Tirz, Reta, Sema, etc.) . It is a big reason VK2735 is likely to succeed in the Maintenance Trial with 2 week titration blocks IMO. @Doctor_Salomon @semodough @pharmdca @GilaMonstrum

VO2 max drops 46% from age 20 to 70, but cardiac output only falls 31%. The gap between those numbers reveals something unexpected about where aging really happens. For decades, the dominant explanation for declining aerobic capacity with age centered on the cardiovascular system. Your heart beats slower, pumps less blood per beat, and delivers less oxygen to working muscles. This narrative made intuitive sense and aligned with the most visible changes of aging. But new research quantifies a different story. The limitation isn't just about oxygen delivery. It's increasingly about what happens after the blood arrives at muscle tissue. VO2 max represents the maximum rate your body can consume oxygen during all-out exercise. It's one of the strongest predictors of longevity and functional independence as we age. Beginning around age 30, it drops roughly 10% per decade in sedentary people. The Fick equation breaks down what determines VO2 max: VO2 max = Cardiac Output × Arteriovenous Oxygen Difference Cardiac output is how much blood your heart pumps per minute. The arteriovenous oxygen difference, or a-vO2 difference, measures how much oxygen your muscles extract from that blood. This equation splits the aging story into two parts: central factors (heart and lungs delivering oxygen) and peripheral factors (muscles extracting and using oxygen). Central limitation comes from declining maximal heart rate, which drops about one beat per minute per year after age 20, and reduced stroke volume as the heart stiffens and large arteries lose elasticity. Peripheral limitation comes from changes in skeletal muscle itself: mitochondrial density and function, capillary networks that deliver blood to muscle fibers, muscle mass, and the enzymes that drive oxidative metabolism. The new analysis reveals that by late middle age, nearly half of the limitation on VO2 max originates in the periphery, not the cardiovascular system. In younger adults, approximately 77% of the total limitation is central and 23% peripheral. Your heart and oxygen delivery system are the primary bottleneck. In older adults, that shifts to roughly 56% central and 44% peripheral. The muscles are catching up to the heart as a source of failure. The most striking finding: oxygen extraction capacity falls dramatically with age. Skeletal muscle extracts roughly 80% of delivered oxygen at maximal effort in young adults. By ages 75 to 80, that figure drops to approximately 60%. That's a 20 percentage point decline in the muscle's ability to use the oxygen the cardiovascular system is still delivering. Four converging biological processes drive this peripheral decline: 1. Sarcopenia preferentially strips away type II muscle fibers, which are rich in mitochondria and oxidative capacity. You lose not just muscle mass, but specifically the muscle tissue most capable of using oxygen. 2. Mitochondrial density and efficiency decline. Mitochondria become fewer in number, smaller in size, and less effective at converting oxygen into usable energy through ATP production. 3. Capillary rarefaction thins the networks of small blood vessels threading through muscle tissue. Fewer capillaries mean longer distances for oxygen to diffuse from blood to muscle cells, creating a bottleneck at the delivery endpoint. 4. Interstitial changes in the space between capillaries and muscle cells further impair oxygen movement. Changes in tissue structure and composition slow the final step of oxygen's journey into working muscle. None of these is catastrophic alone. Together, they compound into something substantial that previous research underemphasized by focusing primarily on cardiac decline. Here's what matters for intervention: • The peripheral factors driving VO2 max decline (mitochondria, capillaries, oxidative enzymes) remain responsive to training well into later decades of life • Endurance training produces the most reliable capillary growth: 13.3% increase in capillary density and 15% increase in capillary-to-fiber ratio over 8-10 weeks • High-intensity interval training (HIIT) delivers comparable mitochondrial gains to endurance training but requires substantially less total time, estimated at 1.7x more time-efficient • Sprint interval training (SIT) generates the fastest mitochondrial signal per minute of any modality, producing 3-5x greater VO2 max improvement per hour of exercise, though it doesn't significantly increase capillary density • Meaningful adaptation begins within two weeks. Roughly 13.7% of total mitochondrial gains from an endurance block occur in the first 14 days • The biological machinery that aging erodes is the same machinery that training can partially rebuild, even in the seventh and eighth decades of life The practical implication: maintaining VO2 max with age isn't just about keeping your cardiovascular system fit. You need training that specifically targets peripheral adaptations, the cellular machinery inside muscle tissue that extracts and uses oxygen. That means prioritizing exercise intensity that creates metabolic stress sufficient to trigger mitochondrial remodeling and capillary growth. Moderate-intensity steady-state exercise improves cardiovascular fitness but generates weaker peripheral adaptation signals than high-intensity work. The framework also explains why training becomes more important, not less, as you age. When you're 25 and 77% of your VO2 max limitation is central, peripheral decline happens quietly in the background. By 65, when peripheral factors account for nearly half the limitation, those quiet changes have accumulated into the primary driver of functional decline. The decisions made in the fourth and fifth decades of life shape the physiological ceiling of the seventh and eighth. Aerobic aging is a slow, cumulative process affecting multiple systems simultaneously. So is the adaptive response to training. The most important variable isn't the perfect training modality. It's consistency across the decades during which the oxygen cascade is quietly remodeling in one direction or the other.