Mufaso retweeted
It’s her little shoes with perfectly tied laces by a mother who loved her that gets me. Now they’re both gone.
A horrific Russian strike in the Kharkiv region. A “shahed” struck people directly – in a park near an ordinary café. Pure atrocity. Six people were killed, including children. A little girl was killed in a stroller – her name was Angelina, she was just over a year old, born in August 2025… Her mother’s name was Inna. She died in the hospital… Another girl who was killed was 11 years old. My condolences to their families and loved ones. Another 14 people were injured, including six more children.
I am grateful to everyone who supports Ukraine under these circumstances and helps us shoot down “shaheds,” shoot down missiles, and stop Russian assaults. These are horrific photos, but behind them are shattered lives and the truth about this war. Lives must be protected. Ukraine needs air defense. You can't think about making money with Russia as long as it continues its asinine war. We ask that sanctions on Russia stay in place as long as the killings continue. We ask America to be strong, and we ask it to apply the Lindsey Graham law. We ask Europe to continue its support. We ask that everything possible be done to bring peace and guarantee security. Ukraine wants peace. It is Russia that has insisted on continuing the killing all this time. The world has enough strength to stop the war. That strength must finally be used – against the murderers.
$VKTX - Oral VK2735 is positioned to be the first oral GLP-1/GIP dual agonist on the market‼️
The SUNRISE oral Phase 3 program targets only ~1,120 patients across two trials (560 each). That is roughly a quarter of the ~4,700 Lilly enrolled in ATTAIN-1 and ATTAIN-2 for orforglipron. 🤔
The smaller program is likely possible because oral VK2735 is the same molecule as SC VK2735, so it can lean on the VANQUISH safety database (~5,500 patients).
This should let oral VK2735 reach market at a fraction of the incremental R&D cost of new-molecule SMOL single agonists like orforglipron.
$VKTX ORAL VK2735 represents the most advanced oral dual GLP-1/GIP agonist in clinical development and has the potential to be positioned as either an induction therapy or in the maintenance setting, increasing the treatment options available to patients and clinicians
Mufaso retweeted
$PTGX UBS initiate
Buy $184 PT three potential drivers of outperformance over next 12mo 1) underappreciated commercial potential of PN-881 ("oral Bimzelx"), which view as $PTGX's most important pipeline value driver, 2) potential upward revisions to the Mimrylo royalty, where 2027/2028 estimates are 89% and 27% above consensus, 3) pipeline optionality from PN-477 (oral/injectable GGG) and PN-8047 (oral hepcidin), neither of which is reflected in our valuation and will have Phase 1 data in 2027.
$PTGX 881 is targeting 17Billion market with NEW ORAL MOA that’s currently dominated by injectables
Mufaso retweeted
$VKTX
Not investment advice, just sharing 10+ years of my experience investing in the biotech sector.
Over that span, 22+ of my portfolio picks were eventually acquired. See my pinned tweet.
Why am I sharing this?
Many of those big wins, and some of you held these positions alongside me, including $STML $PRVB $DAWN $MYOV $JUNO $NARI $HZNP $RLYP $ITCI $KRTX, experienced irrational price action and significant pressure despite positive news, strong fundamentals, and continued clinical progress.
It was stressful watching a position trend lower while the underlying story remained intact.
But looking back, many of those extreme-fear-driven pullbacks turned into some of the biggest opportunities and, ultimately, substantial gains.
If you’ve spent enough time in biotech, you’ll see this pattern repeatedly, especially with clinical-stage companies.
The market can be extremely emotional in the short term. Fundamentals, clinical data, and execution often take time to play out.
You can sell into the fear and potentially regret it later, or, if your thesis remains intact, use those periods of irrational selling to reassess and potentially add.
Patience. Conviction. Execution.
That has been my approach for 10+ years in biotech.
Of course, there will be some losers down the road and that’s just part of the process. Move on and reassess what went wrong.
We can’t control the stock price, but to some extent, we can control our decisions.
Be well!
$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."
Mufaso retweeted
$VKTX I don’t get the pile-on over this offering.
The deal launched at $400M and came out upsized to $500M, with Morgan Stanley and J.P. Morgan on the books. That is not a distressed dump. That is demand. Institutions do not throw hundreds of millions at a name they think is trash especially not the day after strong VK2735 maintenance data.
Retail sees dilution and hits sell. The people writing eight-figure tickets see cash for Phase 3, the oral program, and a shot at a slice of a huge obesity market. They have the model, the calls, and the allocation. The size of the book is the tell.
Strong demand on an upsized deal after good data is the story. Big money does not fund garbage at scale.
I would not be surprised with a big bear trap today.
Mufaso retweeted
$VKTX My July thread aged well — VK2735’s maintenance data reinforces how much cleaner its safety profile is versus retatrutide.
$VKTX Full thread on upcoming Maintenance Study results
Maintenance study is due this quarter, possibly in September. The significance of these results is substantial, and I will explain why in this thread.
Why this is an important readout: First, this trial will give us our first look at 31‑week weight‑loss data; until now, we’ve only seen results through 13 weeks.
Second, the subcutaneous dose is titrated up to 22.5 mg, offering insight into the impact of higher dosing. We’ll also get new information on switching from subcutaneous to oral, along with early signals on weekly oral dosing.
There’s a lot of data here, including the first look at monthly subcutaneous dosing. In total, we’ll be evaluating four distinct dosing regimens: weekly subcutaneous, monthly subcutaneous, daily oral, and weekly oral.
In summary, maintenance study results will also be important for topline data from the oral maintenance study, which will have read-throughs to the Ph3 program. Opportunity for VK2735 may be greater given it's a more potent dual GLP/GIP agonist and will also couple well with SQ VK2735 for seamless transition between SQ and oral formulations.
Advantage $VKTX as SQ VK2735 To Oral VK2735 offers a more seamless transition between Formulations. The fact that both the SQ and oral drugs are identical molecules formulated as oral and SQ. This should help mitigate some of the AEs associated with switching patients between different molecules.
Take a look at when patients were switched from SQ Wegovy or SQ tirzepatide to orforglipron, discontinuation rates went up. In the ATTAIN-MAINTAIN study by $LLY showed that when patients were switched from SQ semaglutide or SQ tirzepatide to orforglipron, D/C rates due to AEs were 4.8% and 7.2%, respectively. Also, patients who switched from Zepbound to orforglipron gained 11 lbs after 52 weeks on orforglipron.
Just a recap on $LLY Obesity portfolio
1) Retatrutide- Triple agonist, weekly subq injection. Efficacy- Weight at 80 weeks from avg. baseline: Retatrutide 4 mg -19.0%, 9mg -25.9%, 12mg -28.3%, Placebo 2.2%.
Safety- The most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg, vs. placebo, respectively) were nausea (28.6%, 38.4% and 42.4% vs. 14.8%), diarrhea (25.2%, 34.1% and 32.0% vs. 13.5%), constipation (23.8%, 25.9% and 26.1% vs. 10.9%), vomiting (10.6%, 22.8% and 25.3% vs. 4.8%), and upper respiratory tract infection (14.2%, 12.2% and 13.1% vs. 11.6%). Incidences of dysesthesia occurred in 5.1%, 12.3%, and 12.5% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% with placebo.
2) Tirzepatide (Zepbound)- LLY's blockbuster drug is a dual GIP and GLP-1 receptor agonist like $VKTX 2735 which is currently in PH3 and reports data in 2027.
Efficacy- Average weight loss with tirzepatide of 26.6% from study entry over 84 weeks, 20.2% compared at 72 weeks
Safety- See the Chart below.
3) $LLY oral drug orforglipron, a small non-peptide for obesity
Efficacy- orforglipron showed placebo adjusted weight loss at 72 weeks of:
• -5.4% for 6 mg dosing
• -6.3% for 12 mg dosing
• -9.1% for 36 mg dosing- this is nothing earth shattering weight loss as it had been touted as the next blockbuster drug. In comparison, $VKTX VK2735 oral drug showed loss of 8.7% at 60mg dose in just 13 weeks. Weight loss of 12.2% at 120mg dose though higher D/C rates and side effects and not likely a viable dose from manufacturing standpoint.
Safety- Higher treatment D/C due to adverse events (10.3% at highest dose vs 2.6% placebo)
Significant gastrointestinal side effects reported (33.7% nausea, 25.4% constipation at highest dose)
Overall discontinuation rate of 24.4% at highest dose indicates tolerability challenges.
The most common adverse events for participants treated with orforglipron (6 mg, 12 mg and 36 mg, respectively) were nausea (28.9%, 35.9% and 33.7%) vs. 10.4% with placebo, constipation (21.7%, 29.8% and 25.4%) vs. 9.3% with placebo, diarrhea (21.0%, 22.8% and 23.1%) vs. 9.6% with placebo, vomiting (13.0%, 21.4% and 24.0%) vs. 3.5% with placebo, and dyspepsia (13.0%, 16.2% and 14.1%) vs. 5.0% with placebo. Treatment discontinuation rates due to adverse events were 5.1% (6 mg), 7.7% (12 mg) and 10.3% (36 mg) for orforglipron vs. 2.6% with placebo. The overall treatment discontinuation rates were 21.9% (6 mg), 22.5% (12 mg) and 24.4% (36 mg) for orforglipron vs. 29.9% with placebo.
Mufaso retweeted
The market still isn't pricing $VKTX correctly, but that's fine. This trial was a major de-risking event
$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. 😊😊😊
Mufaso retweeted
JUST LIKE THAT!!
A cross-border completion from @FitzMagic_14 ➡️ @StevieJohnson13
Mufaso retweeted
$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).👊
$VKTX Full thread on upcoming Maintenance Study results
Maintenance study is due this quarter, possibly in September. The significance of these results is substantial, and I will explain why in this thread.
Why this is an important readout: First, this trial will give us our first look at 31‑week weight‑loss data; until now, we’ve only seen results through 13 weeks.
Second, the subcutaneous dose is titrated up to 22.5 mg, offering insight into the impact of higher dosing. We’ll also get new information on switching from subcutaneous to oral, along with early signals on weekly oral dosing.
There’s a lot of data here, including the first look at monthly subcutaneous dosing. In total, we’ll be evaluating four distinct dosing regimens: weekly subcutaneous, monthly subcutaneous, daily oral, and weekly oral.
In summary, maintenance study results will also be important for topline data from the oral maintenance study, which will have read-throughs to the Ph3 program. Opportunity for VK2735 may be greater given it's a more potent dual GLP/GIP agonist and will also couple well with SQ VK2735 for seamless transition between SQ and oral formulations.
Advantage $VKTX as SQ VK2735 To Oral VK2735 offers a more seamless transition between Formulations. The fact that both the SQ and oral drugs are identical molecules formulated as oral and SQ. This should help mitigate some of the AEs associated with switching patients between different molecules.
Take a look at when patients were switched from SQ Wegovy or SQ tirzepatide to orforglipron, discontinuation rates went up. In the ATTAIN-MAINTAIN study by $LLY showed that when patients were switched from SQ semaglutide or SQ tirzepatide to orforglipron, D/C rates due to AEs were 4.8% and 7.2%, respectively. Also, patients who switched from Zepbound to orforglipron gained 11 lbs after 52 weeks on orforglipron.
Just a recap on $LLY Obesity portfolio
1) Retatrutide- Triple agonist, weekly subq injection. Efficacy- Weight at 80 weeks from avg. baseline: Retatrutide 4 mg -19.0%, 9mg -25.9%, 12mg -28.3%, Placebo 2.2%.
Safety- The most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg, vs. placebo, respectively) were nausea (28.6%, 38.4% and 42.4% vs. 14.8%), diarrhea (25.2%, 34.1% and 32.0% vs. 13.5%), constipation (23.8%, 25.9% and 26.1% vs. 10.9%), vomiting (10.6%, 22.8% and 25.3% vs. 4.8%), and upper respiratory tract infection (14.2%, 12.2% and 13.1% vs. 11.6%). Incidences of dysesthesia occurred in 5.1%, 12.3%, and 12.5% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% with placebo.
2) Tirzepatide (Zepbound)- LLY's blockbuster drug is a dual GIP and GLP-1 receptor agonist like $VKTX 2735 which is currently in PH3 and reports data in 2027.
Efficacy- Average weight loss with tirzepatide of 26.6% from study entry over 84 weeks, 20.2% compared at 72 weeks
Safety- See the Chart below.
3) $LLY oral drug orforglipron, a small non-peptide for obesity
Efficacy- orforglipron showed placebo adjusted weight loss at 72 weeks of:
• -5.4% for 6 mg dosing
• -6.3% for 12 mg dosing
• -9.1% for 36 mg dosing- this is nothing earth shattering weight loss as it had been touted as the next blockbuster drug. In comparison, $VKTX VK2735 oral drug showed loss of 8.7% at 60mg dose in just 13 weeks. Weight loss of 12.2% at 120mg dose though higher D/C rates and side effects and not likely a viable dose from manufacturing standpoint.
Safety- Higher treatment D/C due to adverse events (10.3% at highest dose vs 2.6% placebo)
Significant gastrointestinal side effects reported (33.7% nausea, 25.4% constipation at highest dose)
Overall discontinuation rate of 24.4% at highest dose indicates tolerability challenges.
The most common adverse events for participants treated with orforglipron (6 mg, 12 mg and 36 mg, respectively) were nausea (28.9%, 35.9% and 33.7%) vs. 10.4% with placebo, constipation (21.7%, 29.8% and 25.4%) vs. 9.3% with placebo, diarrhea (21.0%, 22.8% and 23.1%) vs. 9.6% with placebo, vomiting (13.0%, 21.4% and 24.0%) vs. 3.5% with placebo, and dyspepsia (13.0%, 16.2% and 14.1%) vs. 5.0% with placebo. Treatment discontinuation rates due to adverse events were 5.1% (6 mg), 7.7% (12 mg) and 10.3% (36 mg) for orforglipron vs. 2.6% with placebo. The overall treatment discontinuation rates were 21.9% (6 mg), 22.5% (12 mg) and 24.4% (36 mg) for orforglipron vs. 29.9% with placebo.
Mufaso retweeted
$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 MS Ph1 VK2735 maintenance data this month Catalyst Importance: Very High. Catalyst Surprise: Meaningful upside surprise
• Ph1 VK2735 data (injectable: monthly and Q2W) in weight maintenance are
expected in 3Q26 and oral maintenance data are expected 1H27.
• Data from an exploratory oral cohort in Ph2 suggests potential as a maintenance
therapy and provides positive readthrough to the injectable formulation.
• Induction phase designed to maximize early weight loss with an aggressive titration
schedule and thus does not provide read-through on the tolerability profile.
• Expect focus on safety during the maintenance phase given theoretical increased
risk of GI events, while we view <20% vomiting as acceptable.
• Beyond maintenance, 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
of VK2735 compared to approved or other treatments in development.
• We believe flat or continued weight loss during maintenance could drive +25-30%
upside. While a sharp rebound (≥5% weight regain) may pressure shares (-10-15%).
$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:
One observation in $VKTX phase 2 from 2024 is the broad wt loss across population. At 15 mg dose 100% lost > 5% and 89% lost > 10% in 13 wks.
There were 35 pts in this arm and 7 DC drug for whatever reason ( 28 finished the study on drug ) . But 31 pts lost > 10% .. and 35 lost > 5%
it shows that pts didn’t stop early .. there was 10 to 15 mg step up that made a few pts uncomfortable which VK is avoiding in all subsequent studies.
When I look at $PFE Vesper 3 with 24% vomit ( double $LLY TZP) and 20% DC from any reason , I wonder how they will be able to combine with their amylin ( 37% vomit in MAD) ? No wonder they new phase 2 B is like 900 pts as ptiabaky still can’t figure the right combination doses despite doing 200 pt trial in 2025-26
Same issue will face $ABBV if they end up relying on amylin combination with any future asset. And $RHHBY ..
and $NVO is doing now 7.2 mg sema / CagriSema trial 😂
Knowing that a number of pts are de escalation due to excessive wt loss on VK2735 and $LLy retatrutide trials .. not sure if combinations will have serious role in future… or be competitive with excellent single agent approaches
Mufaso retweeted
$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 Rusfertide continues to be an under-appreciated valuable asset. Following Co's opt-out election, Takeda now holds worldwide commercialization rights. The transaction generated a $200M payment. Co is eligible for addti $200M opt-out fee + $75M approval milestone + up to
$775M commercial milestones. Tiered royalties range from 14%-29%. At annual sales of ~$1.5B, mgmt indicated the weighted average royalty rate would be ~21%. $PTGX is slated to pocket $475M in milestones this year from TAK alone.