Summary: CD19/antibody data bullish for AMGN inebilizumab MG readout and ARGX/IMVT; allo/auto CAR-T cell therapy plays ELYM and CGEM face obsolescence risk from simpler antibody approaches.

structural marker; pre-classified as canonical yfinance ticker

Three big takeaways for me from this publication today at first glance:

1)  We see another patient (this time with SSc) who had a deep clinical response despite lack of significant effect on (presumed) pathogenic auto-antibody titers.  This is in line with the recent case study of CD19 CAR-T in MG where a patient had complete & sustained resolution of MG despite no fall in AchR Abs.  Seems relevant to the upcoming $AMGN MG inebilizumab readout.

2)  All of these patients had failed prior IL-6, and then responded to CD19, whether or not auto-antibody levels were reduced.  IL-6 worked but was uncompetitive in MG.  If we are making the leap of cross-comparing indications, then CD19 may be looking like a better target than IL-6 in Ab-mediated diseases.  Again, $AMGN MG readout 👀 $ARGX $IMVT.

3)  Allogeneic CAR-T in I&I has itself a major catch-22.  Allo cell therapy has failed in oncology because it is not potent/durable enough to generate durable responses like autologous CAR-T does.

If further studies continue to corroborate the idea that  the CD19 depletion bar is lower in I&I than it is oncology (as it rationally should be) and allo CAR-T can drive the same degree of deep responses in I&I, allo CAR-T will have proved that it works, but will ultimately be doomed.

Why?  If the bar for depletion really is lower in I&I, then simpler antibody-based approaches (which have already proven durable CAR-T-like efficacy in oncology) will dominate.  Antibody based drugs that can safely and easily be given off the shelf without lymphodepletion and manufactured easily at scale will be just as effective as auto or allo CAR-T.  There would be no reason to use cell-based modalities in this case.  $ELYM $CGEM.

If allo cell therapy proves that it works in I&I, they're basically establishing their own obsolescence by proving that their most threatening competition is going to work as well.

1st clinical data for allo CAR-T in AID, from Bioray Labs in China

Too early for a read on LT durability, but initial response resembles auto CAR-T

I've speculated that 'immune reset' may obviate the need for durable persistence; these data support that hypothesis (1/6)


these $LLY $NVO drugs really aren't very expensive *at all* in the realm of branded drugs. Yet, these will be the only inventions to visibly inflect the life expectancy curve of developed nations since, what? Antibiotics maybe? I think there should be no question that this deserves *extreme* financial reward.

Summary: Bullish LLY and NVO: obesity drugs historically underpriced vs. their world-changing impact; extreme financial reward deserved.

Idk man, these $LLY $NVO drugs really aren’t very expensive *at all* in the realm of branded drugs.  Yet, these will be the only inventions to visibly inflect the life expectancy curve of developed nations since, what?  Antibiotics maybe?

I think there should be no question that this deserves *extreme* financial reward.  Literally to say these drugs change the course of human history is not an exaggeration.

And the most bullish peak sales projections for the obesity market max out at like ~$150B - then they’ll go off patent and do good (cheaply) for mankind forever!

Apple sold $200B of iPhones last year, and did nearly $400B in all-product revenue. When is LOE for them?  Oh yeah, never!

The pharma pricing/revenue hate is misguided IMO.   Cheap (by yearly cost/person) drugs that are massively changing the world for the better, and with the 2 companies making them *combined* the most bullish projections say they’ll never even sniff *half* the revenue of Apple, *AND* the drugs will go off patent someday to become cheap forever.  If anything I’d call that a *fantastic* deal for humanity.

If that setup is “greed” then idk.  Where’s the incentive to discover stuff like this?  IMO this part of the system is working as it should.

@A_May_MD @paulcerro They certainly didn’t make the system, but they’re taking full advantage of it. Same could be said of 503b’s.


Amtagvi at $48.7M in Q4 after having been $42.1M in Q3 is very bad. The therapy is too toxic and logistically complex. I'll say it again - people without some experience in healthcare don't innately appreciate how challenging of a regimen this is to administer. Tox and logistics matter.

Summary: Bearish IOVA: Amtagvi QoQ growth only ~16%, therapy too toxic/logistically complex to scale, market rightly punishes guide-only quarter padded by Proleukin stocking revenue.

This time $IOVA is down because Amtagvi QoQ growth was only ~16%.

The market does not want them to be hitting guide only thanks to Proleukin stocking revenue.

Amtagvi at $48.7M in Q4 after having been $42.1M in Q3 is very bad.

The therapy is too toxic and logistically complex.  I’ll say it again - people without some experience in healthcare don’t innately appreciate how challenging of a regimen this is to administer.  Tox and logistics matter.  Yes, even in fatal cancers!

If you’re long $IOVA and only listening to the permabull biotwitter cult leading pumpers who won’t stop tweeting about how positive the earnings results were, you may be wondering why you’re down 20% right now.

Well, it *does* happen that stocks irrationally trade down on good https://t.co/FjTLTqbomi


I predict you'll lose your shirt, but it'll take a while.

Summary: Bearish TMDX; predicts the long thesis will fail and the parent-tweet investor will lose money, albeit slowly.

@Andre_AGTC Hm, I’ve never posted a single tweet on $AXSM.

Good luck though.  I predict you’ll lose your shirt, but it’ll take a while.

$TMDX  NP
But based on this tweet I am intrigued
Typically Scorpion publish such hit piece at the end of the down run. Plus is happily  amplified by Adam.
All points to good entry
Like inverse Adam/ Cramer  index
The last case like that was $AXSM Year later the stock is +50%


Summary: Bearish VKTX: GI adverse-event rates far exceed LLY's tirzepatide, making weight-loss comparisons misleading; implicitly favors LLY.

No, $VKTX had very high nausea and vomiting rates in the cohort that he posted above.  Much higher than $LLY tirzepatide.

Everyone wants to show you the weight loss from the super high dose of viking while ignoring that the GI AE rates are way higher than Lilly’s.  It’s a misleading comparison.

@A_May_MD @GilaMonstrum What's bad about VKTX' AE profile..?

Mild nausea, zero dropouts when they were consuming zero calories..?


Summary: Sees BBIO launch curse broken by strong Attruby sales; frames it as a buy opportunity analogous to VRNA's successful launch.

Is it just me or does it feel like the $BBIO curse may have finally been broken?  Stock is still a ways off from 52wk highs, but those initial Attruby sales look convincing.

Time will tell, but my guess is that this is another chance to buy at the first sign of a launch outperforming.  Those who did so with $VRNA have been quite pleased!


the door is open for the possibility of some seriously huge projections in the scenario that this become the 'it' drug in COPD

Summary: Bullish on the drug's revenue potential surpassing INSM's $12B comps if it becomes the dominant COPD therapy.

Exactly!  If we really are completely throwing away the recent thinking about the potential market size here (this beat suggests we *should* be doing that) then the door is open for the possibility of some seriously huge projections in the scenario that this become the "it" drug in COPD.

@A_May_MD this could feasibly do more in revenue than $INSM brenso. And that's a $12B company with obviously huge revenue expectations


Summary: Implies TECX sell-off driven by LLY is an overreaction that will reverse, as it did last time.

@bio_clouseau “Yeah we developed a shitty drug” or “yeah we designed a shitty trial” weren’t really options for Dan to say there.

Round 2 of $TECX selling off because of $LLY.  We saw what happened last time.  🫡

$LLY comments on their own relaxin failure put the blame on the relaxin mechanism and not their molecule. But wishes competitors well! $TECX $AZN


Summary: Defends FATE's pipeline value despite stock disaster; bearish SANA as a cash furnace with nothing to show.

@Biotech2k1 @BiomedicalRX Cold take my friend.

$FATE is burning only 10% more cash with an equally large preclinical pipeline and infinity times the number of clinical stage assets (0 vs 7). Discussing multiple registration directed opportunities versus discussing *filing* an IND. Come on man.

---

@Biotech2k1 @BiomedicalRX None of this is to say that $FATE stock hasn't been a disaster. But look what the have to show for the money they're spending (registrational trials upcoming in 23) versus what $SANA has (literally nothing).  Not sure I can find a cash furnace worse than SANA.


Summary: Bullish IBIO as undervalued and undiscovered relative to SRRK.

@Maximus_Holla Like ‘em both!  $IBIO just a whole lot cheaper and seemingly undiscovered!


Summary: Both IBIO and SRRK flagged as the only plays on validated myostatin MOA amid rising industry focus on muscle-preserving obesity drugs.

(1) WSJ article saying $NVS wants to buy muscle-preserving obesity drugs.
(2) Reuters article (today) "Fat, not muscle: drugmakers in race for next weight-loss breakthrough"
When does a microcap like $IBIO start to get some attention here?  $IBIO and $SRRK are really the only ways to play myostatin right now, which is the only MOA that has actually been validated in muscle performance outcomes (albeit in SMA).

---

Maybe this is what $IBIO needs to start getting that myostatin/obesity respect 😅


$IBIO and $SRRK are really the only ways to play myostatin right now


Summary: Bullish SRRK: argues scientific evidence supports myostatin inhibition for GLP-1-induced muscle loss; prior 'failures' were indication-specific, not mechanism failures.

With all the GLP-1 craze that $LLY & $NVO have brought to the market this year, there has been increasing interest in the potential problem of GLP-1 induced muscle loss. With ~1/3 of weight lost on GLP-1s being lean muscle, biotechs like $SRRK studying potential solutions have come into focus. Their drug, a myostatin inhibitor, is being studied with Ozempic to see if muscle can be preserved during profound GLP-1 weight loss, ideally making it so that patients lose fat alone or at least less muscle along the way.

However, the history of myostatin inhibitors is complex.  In certain animals, it is unequivocal that myostatin loss/blockade creates incredibly muscular phenotypes (see myostatin mutant cows). In humans, the evidence is less obvious.  This leads some to conclude that myostatin inhibition alone does not cause increased muscle in humans and that multiple muscle-related pathways must be targeted simultaneously to have an effect (example: blockade of the activin receptor).

While I agree that myostatin inhibition alone won't create humans resembling these massive cattle, my view is the idea that myostatin inhibition can't lead to human muscle growth/preservation goes directly against scientific evidence to the contrary.

For example, there is literally a human genetic model of myostatin loss of function, with the NEJM publishing a case report of a male human born with homozygous myostatin loss of function mutation. Without functioning myostatin, the otherwise healthy child was born with ~2x larger muscles and ~½ the subcutaneous fat of a normal child.

This establishes strong genetic proof of concept that reducing myostatin activity can lead to muscle gain in support of $SRRK's thesis.  But what about in-human studies of others' anti-myostatin drugs?

Some might use Pfizer's Domagrozumab P1 healthy volunteer study to suggest myostatin blockade doesn't work. Granted, the study was small n and short duration, and was noisy as a result, with most treatment arms showing no difference vs placebo. However, the treatment arm with the largest sample size (n=12 vs n=6 for all others) did show a statistically significant increase in lean mass vs placebo after a single dose.  The study also showed stat sig increases in muscle volume and "probable muscle" per T2 imaging.  Noisy, but in any case, the evidence was enough for $PFE to take the drug into P2 for Duchenne's muscular dystrophy.

Again, opponents would say that the DMD studies of myostatin inhibitors further prove lack of muscle effect because the DMD studies failed.  While it is true that these studies (conducted by $PFE and $RHHBY) failed on functional endpoints, they again showed that myostatin drug arms had 2-5% increases in lean/muscle mass.  So why did the studies "fail"?  Well, In DMD, the genetic defect is in the muscle itself, meaning that these myostatin trials may have failed on functional endpoints because they simply increased the amount of defective muscle patients had, not because the drugs didn't increase muscle.  They did - it's just that these patients' muscles don't work properly, so growing more doesn't help.

Opponents of myostatin inhibition may suggest that multiple pathways (including myostatin) have to be blocked via the Activin receptor in order to generate muscle growth.  Interestingly, a drug with this exact mechanism of action (Bimagrumab, recently bought by $LLY) also failed to improve functional endpoints in a muscle disorder (inclusion body myositis) just like myostatin inhibitors did in DMD.  In this study, Bimagrumab increased lean body mass by ~1-5.6% across treatment arms, quite similar to the ~2-5% increases seen in DMD trials of myostatin inhibitors.
 This is further evidence that prior "failures" of muscle-growing drugs may have been the result of the drugs being used in the wrong indications, not that the drugs don't increase muscle.

In closing:  Muscle loss while on GLP1s may be a big challenge in the real world, so people are trying to find solutions.  Who knows which methods will work and which won't.  Perhaps wider blockade of multiple pathways using the activin receptor will be required.   However, my impression from the data to date is that the narrower/more targeted approach of blocking myostatin has as good of a chance at working in this muscle preservation space as any.  Don't forget that any drug being used in the mass market of obesity/DM2 has to be SAFE SAFE SAFE, and you'll want to interfere with as few molecular pathways as possible to accomplish this degree of safety.

---

NEJM Case Study: https://t.co/lM3HvIytQ4
Doma HV Data: https://t.co/l1dHSRu6DW
Doma DMD Data:
https://t.co/TnSBeEtpDN
Myostatin/Activin Review: https://t.co/3neNSFhfDv
Roche DMD data: https://t.co/Oakz7icTWz
Bimagrumab IBM Data: https://t.co/P5PVeECAcl


Despite that, they're already reaching the same ORR as Padcev. Certainly seems suggestive of a better therapeutic window to me, and it's nice to have the objective evidence of lower measured free MMAE to help cement that narrative.

Summary: Bullish CRBP: CRB-701 matches Padcev ORR with far better tolerability metrics and lower free MMAE, suggesting superior therapeutic window.

$CRBP single case of rash resolved without any intervention.  Patients had a high baseline rate of eye disorders, and ocular prophylaxis is very easy to implement if the rates are truly higher.

Hard to parse rates of specific safety events at small n obviously, but shouldn’t we look at “interruptions, reductions, and discontinuations” as the best “global” metrics for tolerability?

Padcev:
-Interruptions = 32%
-Reductions = 51%
-Discontinuations = 14%

$CRBP
-Interruptions = 3%
-Reductions = 0%
-Discontinuations = 0%

The counter to these safety data is that it’s still early and CRBP includes some lower doses in safety, but it looks pretty competitive to me.

Based on those tolerability metrics, one would assume that $CRBP is seeing lower efficacy given that they clearly have not yet pushed the boundaries of tolerability.  Despite that, they’re already reaching the same ORR as Padcev.  Certainly seems suggestive of a better therapeutic window to me, and it’s nice to have the objective evidence of lower measured free MMAE to help cement that narrative.

$CRBP Where does CRB-701 nectin-4 ADC fit in? Selective n gives an ORR of 43% in UC while duration of those responses seem to be relatively short so far though some ongoing. Gr3 AE's popping up(rash, ocular) . Already seeing gr3 eye disorders while Padcev hardly had any gr3.


Summary: Author's two top picks in the space are CGEM and CLYM, citing CLYM's Phase 2 readiness and limited coverage.

Yep there’s very little coverage on the name.  They’ll be in P2 soon as their drug had been studied in other indications in the US already, so the stuff like dose escalation studies that CGEM still needs to do are out of the way for them.

It’s a big space with room for multiple winners.  By a long shot $CGEM and $CLYM are my two favorites in the space.

@A_May_MD I need to look closer at $CLYM then! I think ticker symbol change recently might have caused it to be a little unfollowed too.


Summary: Sarcastic defense of FATE (pairing with top lymphoma drug = bullish) vs bearish swipe at AFMD (bispecific with no approved cell source).

@Biotech777 @dhovekamp42 @JamesFr6_8 @brendan_49 @MattBiotech Yeah, it would be terrible to have a cell therapy that pairs with the most lucrative lymphoma drug of all time ( $FATE)

Would much rather have a bispecific antibody that only works with an unapproved cell source that you literally don’t even have ( $AFMD)

Make that make sense.

@dhovekamp42 @JamesFr6_8 @A_May_MD @brendan_49 @MattBiotech Wishful thinking for $FATE … they will waste SH’s money with #rituximab


Summary: Bullish TECX: stock at $36.45 offers ~50% upside to the $54.14 price a major buyer paid just days ago, with CFO also buying at that level.

The GOAT bought $40M of $TECX *this week*.

At close today, you could already buy $TECX at $36.45.  Nearly 50% upside just to get back to the $54.14 that the GOAT paid not even 5 days ago 🤯

WTF is going on?
$LLY $AZN https://t.co/ueFQWudRtm

---

$TECX CFO also bought a quarter million bucks worth of extra shares (on top of those the C suite apparently just issued for trial success).  Also at the $54.14, a premium price to the funds in the offering.  🤷🏻♂

By the time his investment in his company has even been filed, its value has already gone from ~$250K to ~$168K.


$HIMS personalized dose theory is going nowhere. Not happening. Shortage was the *only* way around this. Over now.

Summary: Bearish HIMS: personalized-dose compounding loophole will fail, drug shortage ended, and composition-of-matter patents block any remaining path for compounders.

Drug Manufacturers - Specialty & Generic

$HIMS personalized dose theory is going nowhere.  This would be a loophole for literally every drug on the market.

“My patient needs 78.5 mg of Vyndaquel, not 80mg.  Better get it compounded for $5 instead of $10,000.”

Doesn’t work that way.  Not happening.  There’d be literally no point in discovering/developing new drugs if compounders could get away with nonsense like that.

---

@cigs1234 @AndrewDudum Sema and TZP have extant *composition of matter* patents.  Compounders aren’t even running a MOU challenge here.  Shortage was the *only* way around this.  Over now.


Summary: Bearish TMDX: device has no patient outcome impact, surgeon adoption reversing, product heading out.

If this $TMDX device disappeared off the face of the planet overnight it would not negatively influence a single patient.  The product has no impact on patients outcomes - even the company says this.

Maybe a few more highly paid transplant surgeons would have to wake up in the middle of the night to do transplants (AKA the job they signed up for), but that would be it.

The product’s entire purpose is to make transplant surgeon’s lives easier.  Given how many transplant surgeons seem to have switched from loving to absolutely despising the $TMDX service, it seems like their product is on its way out.

@A_May_MD @ScorpionFund It would be quite unfortunate if their FDA approval is revoked.

The sheer volume of transplants these guys are involved would be quite harmful to patients. What the report brings up is not new either.

In any case, appreciate you sharing the bear case.


Summary: Selloff in Tecx is overdone given different drug design, diseases, and endpoints vs the binary-result framing.

Tectonic Financial / TECX on Nasdaq; selloff context

I agree, this is same MOA but different drug design, different diseases, and different endpoints.  Wasn’t sure at first but with this in mind I think the magnitude of the selloff here is probably overdone.  Haven’t done any deep diligence here though, so that’s a somewhat superficial take.

@A_May_MD They treating this like it’s a binary result to Tecx which is just not the case. Wild. I hope a lot of this are shorts inside 20 dollars.


Summary: Bullish TIL: $300M market cap vs BNTX's $3B gain on same MOA/stage is a large mispricing gap still to close.

And $TIL halted up.  +$300M ($TIL) versus +$3B ($BNTX) gap really didn't make sense.  How much narrower is the gap now?  Like $100M?

So much for efficient markets.

IMO $TIL can keep going.

$TIL Market cap still ~$300M at the moment.

$BNTX has added ~$3B (~$13/share) following the $SMMT news.  BTNX drug has same MOA as TIL, and is in the same developmental stage.

And Of course $SMMT >$20B market cap.


Summary: Bullish CB1 drug CRBP as GLP-1s (NVO) face suicide-risk headwinds; bearish NVO on safety comparison.

Reminder that both $NVO Ozempic/Wegovy and $LLY Mounjaro/Zepbound had higher rates of suicide in obesity studies than Rimonabant ever did.

CB1 drugs 📈

$CRBP $NVO

Source:  https://t.co/lvvSKmZkiv

Does Ozempic increase the risk of suicidal thoughts? A new study muddles the picture https://t.co/1jW3Y6E14C via @elaineywchen $NVO $LLY


Summary: GPCR favored over VKTX: smaller market cap, cheaper manufacturing scale-up, and more digestible M&A target for pharma acquirers.

The timeline gap between $LLY orfo and $GPCR is much smaller than the gap between $LLY’s TZP and $VKTX VK-2735.

$VKTX is 3x higher market cap than $GPCR.

$VKTX manufacturing scale up would be 10x more expensive than $GPCR small molecule manufacturing scale up.

$GPCR is a MUCH easier acquisition for a pharma to digest than $VKTX.


people are still catching up on $BBIO here in the $30s (not for long IMO but we'll see)

Summary: Bullish BBIO in the $30s; expects price to rise as more investors catch up to the 430-script data.

Yep - I have encountered numerous people who did not realize this, which is one reason I agree that people are still catching up on $BBIO here in the $30s (not for long IMO but we’ll see).

But it’s hard to blame people for not realizing this.  The 430 scripts number is almost hard to believe without thinking that the number was mostly made up of trial patients.  Almost seems too good to be true, but apparently it is!

@HealthcareNinj1 @A_May_MD There on drug - but was not part of the other 400 reported. CEO MADE THAT VERY CLEAR


Quit listening to the permabull pumpers and consider that it's possible things actually aren't going well

Summary: Bearish IOVA: earnings not as positive as permabull camp claims; 20% of Amtagvi revenue wasted on manufacturing failures, raising serious cost concerns.

If you’re long $IOVA and only listening to the permabull biotwitter cult leading pumpers who won’t stop tweeting about how positive the earnings results were, you may be wondering why you’re down 20% right now.

Well, it *does* happen that stocks irrationally trade down on good news sometimes.  But you may want to be open to the idea that the earnings actually weren’t positive and take a look at how expensive these $IOVA revenues are.

Especially the fact that $8.3M was “wasted” on manufacturing Amtagvi that was never given to patients.  This is an EXTREMELY intense and complicated regimen to administer.  There will be manufacturing failures, people will drop out electively or even die during preconditioning (or from advanced disease) before getting Amtagvi.  The result of these problems is spending a LOT of money on making product that never generates any revenue.  A double whammy.

Sure, total revenue exceeded some sellside projects this quarter.  But that $8.3M loss just on “wasted” manufacturing accounts for almost 20% of all Amtagvi revenues on the quarter!  How many sellside projections have $IOVA immediately dumping 20% of Amtagvi revenue into the trash?  Not good.

Quit listening to the permabull pumpers and consider that it’s possible things actually aren’t going well.

Fingers crossed for good NSCLC data this weekend, which could certainly turn things around if resoundingly positive.

---

Ahhhh I’ve been cursed by the $IOVA nut jobs!

Joke’s on him.  It already runs in the family!

Wear your sunscreen folks. https://t.co/7l2v1q8TF4


Summary: Fully positioned in XBI; 100% long the biotech ETF.

Only 100% left $XBI https://t.co/4SWwyJfLlz


Not surprised to see $SRRK as one of the few names pulling a red to green in today's mess

Summary: Bullish SRRK and VERU as the last SMID-bio plays in obesity/muscle space with phase 2 data imminent, after KROS exit and BHVN SMA failure.

Not surprised to see $SRRK as one of the few names pulling a red to green in today’s mess.  With $KROS announcing this morning that they’re out of the obesity/muscle race and $BHVN having already failed in SMA, who else is left in SMID bio?

$SRRK and $VERU are basically all we’ve  got left?  Both with phase 2 obesity data coming soon!

$kros out of the obesity race….

$srrk $regn $veru $bhvn $lly https://t.co/wbw9mjnWar


$SRRK and $VERU are basically all we've got left? Both with phase 2 obesity data coming soon!


Could $SRRK be the best biotech story for 2024? I think the upside here will ultimately be crystalized with a buyout in the relatively near term.

Summary: Strongly bullish SRRK: clean SMA win, competitor failures, obesity optionality, and likely buyout; BHVN had complete SMA failure.

Could $SRRK be the best biotech story for 2024? I first tweeted about $SRRK almost exactly a year ago.  I was bullish at the time, but even I am amazed by how it seems that *everything* has gone right for them (in spite of significant market skepticism).

- They got a *clean* hit in SMA, where they were generally given a very low probability of success.  This could be a multi-billion dollar market opportunity with a significant moat.

- Their biggest competitive threat, $BHVN, had a *clean* (i.e. complete) failure in SMA despite having been thought more likely to work with a broader MOA.  The fact $BHVN didn't even work in a non-amb subgroup analysis where $SRRK did had to have been a very low probability outcome.

- Their other myostatin competitor, $RHHBY, has recently delayed their data.  Their website currently doesn't even have the drug being *filed* until "2027+".  $SRRK will be fully entrenched in this small, tight knit SMA market by then, beating Roche to market by years.

-$RHHBY also chose not to study their drug in Spinraza combo, so even if Roche does hit someday, the Spinraza market is likely $SRRK's in perpetuity.

-On top of everything going right for $SRRK in SMA and everything going wrong for its competitors in SMA...Their mechanism of action is all of a sudden a major target of interest in the largest TAM of all time...Obesity!

-They stumbled upon a massive obesity opportunity, opened a phase 2 trial, had it enrolled ahead of schedule, and will have data presented <6 months from now.  What are the odds that this MOA increases muscle in SMA patients but *not* in obese patients?  Very low if you ask me.

The stock is up >500% from where it was in October.  Personally, given how large and secure the SMA opportunity is now, plus the legitimate obesity shots on goal, I think the upside here will ultimately be crystalized with a buyout in the relatively near term.

$SRRK is probably my vote for best biotech story of 2024!

With all the GLP-1 craze that $LLY & $NVO have brought to the market this year, there has been increasing interest in the potential problem of GLP-1 induced muscle loss. With ~1/3 of weight lost on GLP-1s being lean muscle, biotechs like $SRRK studying potential solutions have https://t.co/Jhms6DopPE


Summary: Concedes AMGN is not expensive at current valuation despite skepticism on tolerability/efficacy of its GLP-1.

@Sanctuary_Bio <50 and <20 is not the same range as LLY and reducing those AEs is also going to mean even less weight loss.

But yeah, the business overall isn’t expensive.

$AMGN have to say I  agree here. Taking share from LLY NVO is tough but this is trading at 4.4x ttm sales, 13x forward p/e. It's not exactly expensive.

Tolerability was my #1 concern,  if DE gets that to same range as tirzepatide, great.


Summary: LLY years ahead of VKTX on oral GLP-1 (Phase 3 vs Phase 1); bullish LLY, bearish VKTX on clinical stage gap.

$LLY $NVO $VKTX $RHHBY @Pharmdca

This is not a “joke”.  Rather, this is what we would call an objective and wholly irrefutable “fact”.

$LLY has already fully enrolled the PHASE 3 study of its oral GLP-1 orforglipron.

Source: https://t.co/DHEba1lQxW

$VKTX is still in phase 1 dose escalation of its oral GLP-1.

Source: https://t.co/hcyiM80tac

$LLY Is literally *years* ahead of $VKTX on oral GLP-1.  Even Cramer knows that.  If this is a surprise to you, you need to stop accepting the lies from $VKTX permabulls at face value.  People are lying to you.

---

Whoops, this is supposed to be the first source (I accidentally double-posted the reference tweet link instead!): https://t.co/LrU3px7D93


Summary: Bullish on SMA launch as the key catalyst; dismisses obesity optionality as already unpriced in the $40s.

Biohaven Ltd (BHVN) on NYSE; SMA pipeline context matches

@AaronRosenblum5 @Maximus_Holla @TheBiotechBear Personally don’t really think there’s any obesity value in the stock at all in the $40s.  SMA launch is going to be 🚀

@A_May_MD @Maximus_Holla @TheBiotechBear Not sure how excited market will be by obesity results then.


Summary: AMGN's trial design and steroid-tapering label claim give it a competitive edge over ARGX that the market underappreciates.

Of course it does affect the adjusted effect size.  It’s a forced downtitration design.  If a placebo patient is flaring badly but you’re forced to taper steroid, do you think they stay on trial for 24 weeks just for the fun of it?  No, they drop out of the trial.

So the *worst* responding placebo patients get censured/not included in the analysis.  Only the placebo patients who **didn’t** flare badly with steroid withdrawal and could handle 24 weeks of reduced steroids get counted in the analysis against the drug.

This absolutely shrinks relative effect size.

That is the point being made here:

https://t.co/rBePj80gVJ

---

Besides the *fact* that this type of design can lead to reduced delta as explained above (making the $AMGN vs $ARGX a lot more favorable for $AMGN than people may initially think) , the other big thing here is that the $AMGN trial was prospectively designed to assess steroid tapering abilities.

This means they can actually market this aspect of the drug.  They can put it on the label.  It’s an “official” benefit of the drug, versus just weaker post-hoc data on this for FcRns.  That’s a huge advantage in a competitive market.

Whatever you think about comparing these drugs right now, one of them is going to have a label that says it reduces steroid burden, and the other won’t.


Summary: Bearish HIMS: GLP-1 revenue loss will expose underlying business deterioration; calls YTD gains unwarranted.

Incredible how many $HIMS bulls have continued to say that GLP-1 revenue was only 5-10% of their business (based on literally nothing - just some BS some twitter pumpers made up and everyone believed them).

The GLP-1 hose is about to dry up and expose slowing to eventually negative growth in the rest of the business.  Good luck to longs that are still up 35% YTD for no reason while the rest of the market has dipped.

HIMS & HERS $HIMS maintained at 'Underperform' at Bank of America, with a $22 price-target (from $21):

"February observed sales per Bloomberg Second Measure (BSM) data suggests GLP-1 sales growth is accelerating, supporting near-term upside to Street estimates while core growth


Tim Springer is the GOAT. $TECX now looking like a YES.

Summary: Bullish TECX after hitting a key target; author vouches Tim Springer's track record and expects oversubscribed offering.

$TECX hits.  Tim Springer is the GOAT.

"Wouldn’t be the first (or 2nd) time that a Tim Springer company was able to hit a target that others didn’t think they could ($SRRK $MORF ¿$TECX?)" ➡

$TECX now looking like a YES. https://t.co/wyLs2TkvKY

---

$TECX

Next step:  Oversubscribed offering.

Question:  Tim participation Y/N?


Summary: Bullish on VRNA, TARS, and SRRK as buyout targets; long all three.

Alright I swear I’m not going to make a habit out of this, but I’ve got to add $SRRK to the list.  I don’t think $SRRK is going to be around for much longer.

$VRNA $TARS $SRRK

Just for fun and since I’m apparently “too negative” - I like $VRNA and $TARS as buyout targets.

Posting this is almost certainly the kiss of death to ensure it never happens, and the fact that I’m long both makes me heavily biased, but I’m here for style points if it actually


I've got to add $SRRK to the list. I don't think $SRRK is going to be around for much longer.


Summary: Bullish on Janux; believes PSA99 responses will prove durable, comparing to AMAM/PNT/ECYT which were all acquired despite similar skepticism.

@JackSha90859576 This is exactly what everyone said about $AMAM $PNT and $ECYT all got bought out.  That many PSA99s will translate to real/durable responses, especially with IO being the modality, IMO.

@A_May_MD Janux recent update data was highly curated and caveat-laden. PSA response rates look stellar, but Recist ORR is less impressive and would look downright mediocre if you discount the unconfirmed ones.


Summary: Bullish on Viking; bull case intact even if drug is tirzepatide-similar, as that drug is arguably the most valuable ever.

@NickJamesMD And none of this means there isn’t a bull case for Viking!  You can totally still make a bullish case accepting that it is a similar to tirzepatide…likely the most valuable drug of all time!

It's healthy to have these discussions and counter points to the strong $VKTX following. For disclosure, VKTX is one of my biggest positions and will remain so, but one must remain realistic and seek and accept the truth. Still bullish on a BO or partnership by year-end or latest


Summary: Bullish IBIO: obesity muscle-preservation narrative gaining traction, NASDAQ uplisting as catalyst, author sees the move as just beginning.

$IBIO finally starting to catch somewhat of a bid.  Has felt like a matter of time with basically everyone (pharma, news outlets) starting to talk up the obesity muscle issue as the next hurdle in the obesity market over the last few months.  The $IBIO setup at this price has seemed so obvious, but in this awful biotech tape I guess even obvious setups are completely bidless.

Maybe the $IBIO NASDAQ uplisting is playing a role.  In any case, hopefully it’s just getting started.

(1) WSJ article saying $NVS wants to buy muscle-preserving obesity drugs.
(2) Reuters article (today) "Fat, not muscle: drugmakers in race for next weight-loss breakthrough"
When does a microcap like $IBIO start to get some attention here?  $IBIO and $SRRK are really the only


Summary: Bullish BBIO: 400+ prescriptions all from new patients, not trials — characterizes launch momentum as insanely strong.

@semodough And the fact that none of the >400 Rx they already have were trial patients.  Insanely hot out of the gate.

$BBIO - one nugget many probably missed other day was 77% of Medicare lives in equal formulary position to tafamidis) in 5 weeks - outstanding job by $BBIO MGT  - incredible in only 5 weeks - Usally it would take most 9-12 months - market still digesting the $BBIO call


1,000 other companies are going to be doing the same thing. No moat. They have nothing proprietary, literally by their business model's own definition. It's poetic that this will someday be $HIMS downfall

Summary: Bearish HIMS: no moat, nothing proprietary, 1000 competitors can replicate the model; recent pump unsustainable.

Which is why 1,000 other companies are going to be doing the same thing.  No moat.  They have nothing proprietary, literally by their business model’s own definition.  It’s poetic that this will someday be $HIMS downfall since their recent pump came from circumventing the legal moat protecting GLP-1 inventors.

$HIMS business model is to sell you controlled substances legally if you can lie on a survey online

And you’re short this, anon????


Summary: Bearish HIMS: GLP-1 market lost, lawsuit risk from NVO, fundamentals weakened; stock should already be in the $20s from current ~$35.

➡ $HIMS is still up ~40% YTD at ~$35
➡ $NASDAQ down ~10% YTD

YTD $HIMS also lost the GLP-1 market that they were telling people they’d maintain through most of 2025, and should be buckling up for massive lawsuits from $NVO for this “personalized” GLP1 nonsense.

Are $HIMS longs really comfortable owning a name that is up 40% YTD despite it’s fundamental case having objectively weakened due to GLP1 shortage resolution, all while the rest of the market is crashing around it?

$HIMS should already be in the $20s, in my opinion.

Personally think longs should be very nervous at the $35-$37 level we are seeing in today’s market bloodbath.


Summary: Long ELYM and CGEM; short IMVT and ARGX based on chart/arrow signals.

📈 $ELYM $CGEM
📉 $IMVT $ARGX https://t.co/af2a1zy2Wv


Summary: Bullish PTGX for succeeding with IL-23; bearish DICE on flawed efficacy data vs comparators.

Still don't know why $LLY paid up for this $DICE "proof of concept".

Props to $PTGX for actually pulling it off with IL-23 though.  $LLY discontinuing their $DICE IL-17 program that they paid $2.4B for surely can't hurt!

Doubling down on this issue for $DICE

They attempt to compare their wk4 PASI reductions in mild patients to their competitors who enrolled moderate patients.

DICE Population: Baseline PASI = 6.7
Comps: Baseline PASI = 19-20

You can't compare efficacy between these populations.


They're literally in 2nd place for this MOA. Plenty of early stage fast followers out there with much larger valuations on much smaller TAMs. I don't see an issue here.

Summary: Bullish TIL: undervalued vs BNTX readthrough, 2nd-place MOA position justified given peers trade at larger valuations on smaller TAMs.

$TIL has increased <1/10 the market cap value that $BNTX has increased on this news.  Is that not little enough for you?

They’re literally in 2nd place for this MOA.  Plenty of early stage fast followers out there with much larger valuations on much smaller TAMs.  I don’t see an issue here.

What was $TRIL’s n when they started getting credit from $FTSV readthrough?  🤷🏻♂


Summary: Bullish LLY; predicts tirzepatide will succeed in Hidradenitis Suppurativa, expanding its indication pipeline.

Next up, Hidradenitis Suppurativa.

And it will work too.

🔮

$LLY

$LLY recruiting in a Ph3 trial (NCT06588283) of
Ixekizumab Concomitantly Administered With Tirzepatide in Adults With
Moderate-to-Severe Plaque Psoriasis and Obesity or Overweight


Summary: RFK Jr. hostility toward GLP-1 drugs keeps obesity-drug names under pressure near term.

Looks like the RFK Jr. situation probably keeps obesity names under significant pressure in the near term 😬😬😬

$LLY $NVO $VKTX $AMGN $ALT $TERN $GPCR $ZEAL

RFK Jr, who’s pledged to make a significant dent in chronic diseases including diabetes in the U.S. within 2 years, says Ozempic is sold to Americans because “we’re so stupid and so addicted to drugs” https://t.co/YaCZnsZyw4


There was, in fact, nothing to pull $VKTX out of a downward drift back to the $40s. Not going to lie though, it's been more of a crash than a drift. $VKTX is at the very beginning of a huge catalyst desert for the obesity franchise.

Summary: Bearish VKTX; crash ongoing with no near-term catalyst as obesity franchise enters prolonged catalyst desert.

Narrorator: “There was, in fact, nothing to pull $VKTX out of a downward drift back to the $40s.”

Not going to lie though, it’s been more of a crash than a drift.  I didn’t expect it to go this fast.  Troubled macro market doesn’t help the fact that $VKTX is at the very beginning of a huge catalyst desert for the obesity franchise.

$VKTX

Now what’s the catalyst to pull it out of a downward drift back to the $40s where it recently traded? https://t.co/Pe5LXvUkIC


Summary: Bullish BNTX: PD-L1 x VEGF data looks excellent vs KN-789 pembro+chemo comparator that failed on OS with 29% ORR.

@BertrandBio $BNTX comparator study KN-789 you think?  Pembro+Chemo in this setting *failed* on OS and had ORR of 29%.
https://t.co/acMdvJsfGB

These results look excellent if that is an appropriate comparison.

$bntx pd-l1 x VEGF in 2L+ EGFRm NSCLC #esmo24 $smmt $til https://t.co/L37bAU6KWT


Summary: Bullish PHVS over NTLA in HAE: oral pill shows superior efficacy (93% attack reduction) vs NTLA's gene editing with uncertain long-term safety.

For anyone still clinging to hope for $NTLA in HAE, you might want to refresh on what the treatment landscape looks like.  Injectables already dominate the market, and $PHVS has a safe once-daily oral pill coming that looks *more* efficacious than $NTLA.

$PHVS with 93% attack reduction at 18 months.  $NTLA doesn't provide a specific number for that timepoint of course, but doesn't look much better than their 79.5% during the observation period.

Why would you choose to be one of the first humans to have your genome experimentally edited with uncertain long term consequences when you could just take a pill once a day (something most HAE patients are *ALREADY* doing anyway...)?


Why would you choose to be one of the first humans to have your genome experimentally edited with uncertain long term consequences when you could just take a pill once a day


Summary: Bullish BBIO: 90%+ Attruby adoption among naive patients means stock is massively underpriced if even a fraction of cardiologists are behaving similarly.

$BBIO 90% of “incident” population to Attruby???

LOL.  This is not priced *close* to correctly if even a fraction of cardiologists are behaving this way.

Mizuho $BBIO Outperform Salim PT $53.00
Attruby Doc Call ==> ~90%+ of Naive Pts on Attruby; 25 patients by one KOL -Smooth Reimbursement Process; and More
Yesterday, we hosted a KOL call to discuss Attruby's US early launch and the broader ATTR-CM landscape


He appears to be participating in this $TECX (post-Data!) PIPE ***at a premium to the other investors on the deal*** ... Absolutely a thing of beauty to see founders/insiders doubling down like this.

Summary: Bullish TECX: insider Tim Springer buying post-data PIPE at a premium to other investors, seen as strong founder conviction signal.

$TECX Tim Springer remains well and truly GOATed.  He appears to be participating in this $TECX (post-Data!) PIPE ***at a premium to the other investors on the deal***

Has anyone ever seen this before?  There might even be multiple insiders buying at a premium to the funds on this deal given the PR uses the plural form...

Absolutely a thing of beauty to see founders/insiders doubling down like this.

$TECX hits.  Tim Springer is the GOAT.

"Wouldn’t be the first (or 2nd) time that a Tim Springer company was able to hit a target that others didn’t think they could ($SRRK $MORF ¿$TECX?)" ➡

$TECX now looking like a YES. https://t.co/wyLs2TkvKY


$HIMS is in big time trouble... Not for long!

Summary: Bearish HIMS: WSJ exposé on medical malpractice, deceptive ads, loophole exploitation, and incoming lawsuits from NVO and regulators will end the +35% YTD run; incidentally bullish NVO pursuing GLP-1 IP enforcement.

A scathing article on $HIMS was just published this morning by the Wall Street Journal.  It includes a case study of a gentleman whose "genitals shrank and changed shape" on one of the $HIMS hair loss treatments.

Doctors interviewed have noticed a "steady increase" of you men seeking treatment for "very very common" side effects from their treatments.

The article discusses how they are exploiting loopholes to avoid disclosing side effects in ads, and notes that US Senators are already taking action against $HIMS for this.

On top of that, the WSJ highlighted $HIMS insanely lax medical standards.  They stopped requiring photos of the patients' scalp in order to prescribe hair loss medicine (which, as a board certified dermatologist, I can tell you is absolutely ridiculous and would easily yield a malpractice case for failure to examine the patient in "real life" medicine).  Competitor companies like Keeps and Ro both still require this OBVIOUSLY necessary step.  $HIMS eliminated it because it reduces their efficiency in pumping out drugs to whoever asks.

The Journal tested $HIMS out itself, submitting an intake at 11:18am, and received a follow up text that the prescription was already written at 11:19am!!!  There is clearly no medical deliberation whatsoever occurring at this pill mill.

$HIMS is in big time trouble.  The GLP-1 shortage is over.  $NVO will be suing them soon for this "personalized GLP-1" loophole nonsense.  Lawsuits around deceptive advertising practices are clearly inbound as well (that Super Bowl ad is going to wreck them in the long run).  So many patients are having severe side effects from $HIMS treatments that they weren't counseled on that the *Wall Street Journal* is writing articles about it.  The company is clearly behaving as a pill mill, turning out prescriptions in under 60 seconds without reviewing adequate patient information.

Oh, and $HIMS stock is still +35% YTD while the rest of the market has been crashing?  Hmmm...Not for long!

https://t.co/Lcvxnk7lX8


$NVO will be suing them soon for this "personalized GLP-1" loophole nonsense


Summary: Bullish IBIO and SRRK as undervalued myostatin plays for muscle preservation in obesity, with NVS actively seeking acquisitions in that space.

This WSJ article from just a few hours ago highlights $NVS flat out saying that they want to acquire drugs to help with the muscle-preservation problem in obesity.

I don't really understand why companies like $IBIO aren't getting more love in this environment.  The early stage of their drug likely roughly matches that of $NVS in-house obesity program.  $IBIO's Myostatin MOA is probably the single best-validated muscle-sparing approach that there is, with squeaky clean safety and *functional endpoint* validation from SMA.

I guess you could maybe make the $NVS + $SRRK argument too, but that might be a little awkward given that apitegromab was never studied with Zolgensma.

Anyway, I guess this i just my observation on what I see as a strange disconnect.  Pharmas are repeatedly saying that muscle preservation in obesity is an area of interest, yet I can't point to any valuations in the public SMID biotech sector that reflect that.

As I noted before (keeping in mind that I'm talking my book here):  Almost everything for muscle preservation in obesity except myostatin (which was already the best-validated to begin with) has failed.  Pharma is still saying that they are interested, but the myostatin-for-obesity narrative still can't catch a bid?...

https://t.co/XodcVidX5z

$SRRK $IBIO $VERU $BHVN $KROS $REGN $LLY $NVO $VKTX $BIOA $AMGN

I think that $SRRK and $IBIO have an underappreciated opportunity to shake up the obesity landscape with their muscle-preserving myostatin approach. 💪

Some may argue that $SRRK & $IBIO are seeking to solve


I guess you could maybe make the $NVS + $SRRK argument too


It's >50% downside to its 200dma ($23). Losing GLP1 was the worst thing that could happen to them, and it just did. Stock is overextended.

Summary: Short HIMS: GLP-1 loss shrinks the business materially; stock overextended with >50% downside to 200dma at $23.

Mmm sure.  But it was a major part of the $HIMS  business right?  And it’s gone now.  So why would it trade above where it did barely a week ago?  Which was also an all time high.

This was literally in the $20s almost all of last month, and their business is now objectively smaller than it was then.  It’s >50% downside to its 200dma ($23).

Losing GLP1 was the worst thing that could happen to them, and it just did.  Stock is overextended.

@A_May_MD @Mr_Derivatives It was and still is not their primary growth driver


today's action is exactly what $XBI needs… All necessary steps in the direction toward biotech no longer being the worst sector in the market

Summary: Bullish XBI: macro rotation away from tech/indices needed for biotech re-rating; current selloff is a necessary step toward biotech outperformance.

Was talking about this yesterday.  Would’ve guessed biotech was green yesterday if my only datapoint was the 10y.  Certainly wouldn’t have guessed -2% 😅.

Macro wise, biotech investors need to be rooting for the “major” indices and hot tech stocks to come down significantly, don’t we?

Even if it means some short term pain in biotech, a rotation to bio isn’t going to happen while these blue chips just grind to ATHs every single month.

Feels like we would rather have
XBI -2% & NASDAQ -1% right now than
XBI -1% & NASDAQ +0.2% like we have been having for several years.

---

Like maybe I'm just @BagholderQuotes mode here, but today's action is exactly what $XBI needs.  Yeah it's down almost 2% right now and everything is basically on fire, but:
➡10Y -2.4%
➡NASDAQ -1.7%
➡Bitcoin -8%

All necessary steps in the direction toward biotech no longer being the worst sector in the market 😅

Might be heading for a @pawcio2009 BioHell upgrade before long honestly.


Summary: AMGN weight-loss drug shows same efficacy but worse tolerability vs LLY/NVO; expects AMGN down, LLY/NVO/VKTX up today.

$AMGN $LLY $NVO $VKTX
So $AMGN basically has the same weight loss as $LLY TZP (everyone expected much higher) with ~20% at 1 year.

$AMGN also apparently is looking for lower priming doses to give "under 50% and under 20%" nausea and vomiting.  $LLY TZP does 31% and 12% respectively...$AMGN won't even show us the numbers on nausea and vomiting in that entire presentation.

Same efficacy and worse tolerability than what's already on market...I'd expect $AMGN down, $LLY, $NVO, $VKTX up today.

Did they just say that reducing the priming dose significantly lowered nausea and vomiting to under 50% and under 20%?  Did I catch that right?  $AMGN


$LLY could dose higher too for the same results... Tirzepatide discontinuations are lower than placebo at 72 weeks. 15% discontinuations in 72 weeks for $LLY versus 26 in 13 weeks for $VKTX

Summary: Bearish VKTX: efficacy advantage is dose-dependent with poor tolerability (26% dropout in 13wks); bullish LLY by contrast on superior tolerability at 72wks.

@mtheory11bio Exactly.  Look how much worse the $VKTX efficacy is if you only look at the lower (comparable tolerability) doses and move back a week.

They’re just giving more drug.  Not a better drug, just more of it. https://t.co/W3FzcUCnn4

---

$LLY could dose higher too for the same results, but why market a dose where ***26% of patient discontinue therapy within 13 weeks***!

Tirzepatide discontinuations are lower than placebo at ***72 weeks***.

15% discontinuations in 72 weeks for $LLY versus 26 in 13 weeks for $VKTX.

The drugs are the same design and mechanism.  The data says they’re likely getting essentially the same results dose/tolerability adjusted.

Looking at all this data, do you not agree?


I own more $NKTR today than I did yesterday, and I have yet to sell a *single* share. … its enterprise value is still ~$100M...which puts it at less than half of the EV that $QTTB, $ANAB, and $CRVS all had *BEFORE* their atopic derm readouts … $NKTR's EV could pretty easily become *negative* again at these prices if they are able to out license the dapi royalty

Summary: Still long and adding NKTR post-AD hit; EV below pre-data comps that failed, with dapi royalty/LLY lawsuit/alopecia readout as additional catalysts.

🚨PITCH ALERT🚨 $NKTR
Currently at $0.676, representing a  ~0.45x cash multiple and approaching an atopic dermatitis (AD) readout that has a legitimate chance at success, $NKTR represents one of the most compelling risk/reward profiles I have ever seen in small cap biotech.

This thread provides a very basic overview of the setup.  For greater depth, I have provided a link to a much longer pitch at the end of this first "slide".

Although I am clearly bullish (and long) $NKTR at its current prices, I am NOT arguing that their AD readout has an atypically high probability of success (POS).  Rather, I argue that its POS is being underwritten as *zero* in spite of encouraging P1b proof of concept (POC) data.

I will analyze NKTR's MOA, existing data, competitor data, financial position, and the (much larger) valuations that have recently been ascribed to similar AD readouts that clearly had much weaker rationale than $NKTR going into data.

For those looking for greater depth than this thread provides, here is the link to the pitch (via Google Doc):
https://t.co/Li9AZZUhVC

---

$NKTR's P1b Trial:
➡Had a relatively robust n=43 sample size.
➡Tested 2 dose levels against placebo.
➡Dosed patients for only 12 weeks (16 wks is typical for most AD induction studies)
➡Was run by $LLY, as they had partnered on this compound in 2017

To understand my $NKTR pitch, we have to analyze the P1b AD data through 3 different lenses:
1⃣ $LLY's Initial 🚨Erroneous🚨analysis (Sep ‘22)
2⃣ $NKTR's Reanalysis at week 12 (Aug ‘23)
3⃣ *My* Re-reanalysis at week 10

---

This might be the most important portion of the $NKTR story to understand.

🧑💼Analysis 1⃣:  $LLY’s 🚨Erroneous🚨 analysis

INCORRECT Week 12 data below:
➡ Mean EASI reduction of 66% (18% Pbo adj)
➡ EASI75 rate of 29% (9% pbo adj)

Although the mean EASI reduction of 66% in this analysis might suggest activity, the 9% pbo-adj EASI75 rate is awful.  This is a program killer.  The worst comp on the market is the recently launched Nemluvio, with a 13% EASI75 delta.

This $LLY analysis made NKTR’s drug look dead on arrival when released in 2022.  $LLY divested the seemingly worthless asset back to $NKTR, and investors abandoned the stock. However...

🧑💼Analysis 2⃣:  $NKTR 12 week data
A year later we discovered that $LLY had misanalysed NKTR’s data completely.  The properly analyzed data showed much greater signs of activity:

Corrected Week 12 data below:
➡ Mean EASI reduction of 83% (36% pbo adj)
➡ EASI75 rate of 41% (21% Pbo adj)

Comparing to the AD leader Dupixent, the mean EASI reduction is stronger (83% vs 72%), however, the key endpoint of pbo-adj EASI75 rate is worse (21% vs 33%).

So, NKTR’s week 12 analysis clearly suggests that the drug is active and may compete against “lesser” AD drugs, but not against $REGN’s megablockbuster Dupixent.

🧑💼Analysis 3⃣: *My* Re-reanalysis at Week 10

In addition to the bad luck of $LLY’s misanalysis, $NKTR also seems to have suffered from a very unlucky primary efficacy analysis timepoint due to 2 factors:
      ↪Bad Luck #1:  IMO, an EASI75 responder patient no-showed their Wk 12 appointment, making this responder not count toward the Wk12 PE.
      ↪Bad Luck #2: Wk12 was the ONLY timepoint throughout the entire 48 week study (with 18 total efficacy assessments) where there were 2 EASI75 responses on placebo instead of 1 or 0, thus making the Wk12 Pbo-adj EASI75 rate 10% lower!

Absolutely terrible luck for $NKTR🤦♂🐈⬛

With this (re)reanalysis at week 10, we would have:
➡Mean EASI reduction of ~85% (~55% pbo adj)
➡EASI75 rate of 53% (43% pbo adj)

These numbers make a much stronger case for $NKTR, now showing a 43% EASI75 delta that compares much more favorably to Dupixent’s 33% EASI75 delta.

Bonus:  Another source of bad luck? 🐈⬛
Also note that even at week 12, $NKTR’s mean EASI reduction is greater than P3 studies of Dupilumab and Lebrikizumab showed, yet the EASI75 rate is lower.  Mean EASI reduction higher & EASI75 rate lower  suggests that $NKTRs patients were getting close to, but falling just shy of, hitting the EASI75 threshold.  Bad luck again (!!!) and another signal that the data are actually more impressive than they look at face value.

See the attached figures to...
1⃣Visualize the phenomenon of an EASI75 responder missing their week 12 appointment
2⃣Track how the $NKTR data look dramatically different from the initial $LLY mistake, to the reanalyzed Wk12 datacut, to my Wk10 re-reanalysis

---

In the prior slide we see how the $NKTR AD data may be far more encouraging than even the reanalyzed dataset suggests when one looks closer.

🤔Is it possible that $NKTR could reach Dupixent-like efficacy❓
          Yes! ✅
🤔Is Dupixent-like efficacy necessary for $NKTR's readout to be “positive”?
            No! ❌

Attached you will see a larger breakdown of atopic derm comps, which shows that many newer AD drugs  have worse efficacy than Dupi/Lebri, but still being advanced as valuable assets by pharma.

Even Nemolizumab with undifferentiated Q4W dosing and a paltry 13% EASI75 delta (🤮) was just recently launched in AD.  OX40 drugs with 19-29% EASI75 deltas are being hailed as potential blockbusters (by $AMGN and $SNY respectively).

In that context, NKTR’s 21% Wk12 & 43% Wk10 EASI75 deltas look especially encouraging if a number somewhere in the middle can be replicated in P2b.

---

$NKTR
Response Durability → $NKTR’s secret weapon?
                                    🤫🔫🤫

$SNY’s megablockbuster Dupixent is dosed Q2W.  $LLY is about to challenge them with Lebri’s comparable efficacy and Q4W dosing.  Down the road, the $2.4B dollar company $APGE will be pursuing these same MOAs with YTE-modification allowing for possibly Q12W dosing.

In addition to bringing an alternative MOA to the IL4/13 cluster that $REGN/$LLY/$APGE are crowding into, less frequent dosing would be a key way to garner AD market share.

$NKTR’s upcoming P2b readout will be a 16wk induction period only, but the study will continue for longer with arms testing very sparse Q12W dosing.  Showing the ability to dose Q12W in AD maintenance would be a massive win for $NKTR.

Although we won’t be able confirm Q12W dosing success in the 2nd quarter readout, $NKTR’s P1b dataset showed that Rezpeg’s responses appeared to be atypically durable, lasting 36 weeks AFTER the final dose of the drug!  🤯

This suggests that $NKTR has a real shot at achieving the valuable differentiator of less frequent dosing!

Attached, you can see:
1⃣My analysis of NKTR’s response durability (including caveats!)
2⃣NKTR’s P2b study design with Q12W maintenance arms

---

$NKTR is too cheap - Let's use case studies to support this!

From the data presented above, my personal takeaway is that NKTR’s P1b dataset provides the most compelling proof of concept for a pre-phase 2 mechanism of action that I have recently seen in AD.  Yet, NKTR’s price is currently reflective of pure, unabated skepticism.

In fact, NKTR is so cheap that it's hard for me to grasp without using recent case studies as reference...

Let’s examine NKTR’s current valuation in the context of the valuations that 3 similar companies have held into comparable AD readouts all within the last 3 months (detailed calcs shared in the linked doc):

NKTR’s Valuation:  With ~$280M cash, ~185M shares outstanding, and a current share price of $0.676, NKTR is trading at LESS THAN HALF CASH, with a cash multiple of roughly 0.446x.
   ↪ Validation:  P1b data showing encouraging Wk10-12 response rates
   ↪ Valuation into data:  ~(-$150M) Enterprise value

 1.) $QTTB Case Study
   ↪Validation:  Negative validation.  There was no QTTB POC data and the TSLP MOA had already failed for other drugs in AD
   ↪Valuation into data:  +$208M
💰NKTR upside to this pre-data EV:  283%

2.) $ANAB Case Study
↪Validation:  None.  BTLA MOA never before tested in AD, failed in multiple other indications.
↪Valuation into data: +$245M (this is a nuanced #...See doc)
💰NKTR upside to the pre-data EV:  320%

3.) $CRVS Case Study
↪Validation:  None.  ITK MOA never before tested in AD.
↪Valuation into data:  $475M
💰NKTR upside to the pre-data EV:  503%

As all of these case studies show, each company had WORSE proof of concept for their upcoming AD data being positive than $NKTR does, yet these companies all held valuations comprising >3-5x multiples of $NKTRs current valuation.

All of these companies got significant value ascribed to wholly unvalidated AD readouts.  Why should $NKTR trade at a deeply negative EV with their superior validation and AD data 1 quarter away? 🤔

---

$NKTR Pitch Summary Slide

➡$NKTR has P2b AD data for Rezpegaldesluekin in Q2 👨🔬
➡Rezpeg has been forgotten after a misanalysis of AD data by Lilly in 2022 ⚠
➡Reanalyzed data are much more encouraging, and my re-reanalysis of these data shows there may be even more reason for optimism 📈
➡NKTR’s AD program has been plagued by TERRIBLE luck 🐈⬛
➡IMO NKTR has a shot at dupi-like efficacy, which could yield a 10x scenario from $0.676🤞
➡The possibility of Q12Wk dosing is real, and a potential game-changer for Rezpeg’s use case 💉
➡Even if moderately active, current AD comps suggest Rezpeg would have real value, making the ~0.45x cash multiple that $NKTR currently trade at seem wildly inappropriate 🫰

🚀Although caveats abound, $NKTR’s current valuation might be the best risk/reward skew I have ever seen in small cap biotech.

📒Read my (much longer) pitch document attached in the first slide and give me feedback!

Bonus:  I also recommend purchasing the transcript of a very recent @Slingshot_Invst interview on this topic with Key Opinion Leader Jonathan Silverberg.  I have not discussed the interview at all here or even in my longer document, but it is FULL of great detail.  The transcript is well worth a few bucks if you are interested in the $NKTR setup.

---

Yesterday there was a massive development for $NKTR, which seems to have been largely missed.  IMO, yesterday confirmed that $NKTR is sitting on a "secret" or "undiscovered" asset that may now be worth ~100% upside to its market cap.  If you read my full pitch (linked in first slide) you saw discussion of $NKTR's rights to Dapirolizumab milestones and royalties.  However, when I published the pitch 4 days ago, there was really no way to accurately benchmark that asset's current value, so its discussion and attribution to $NKTR's value were minimal.

What changed yesterday was $RPRX paying $250M for mid-single-digit royalties on a lupus drug (Liftilimab) that is highly similar to $NKTR's Dapi.  Since $NKTR owns "low-single-digit" royalties on Dapi, we can roughly argue that Dapi represents ~$125M in NPV to $NKTR, which is roughly equal to $NKTR's entire market cap alone and exclusive of the $40M in Dapi developmental/regulatory milestone eligibility that $NKTR also owns.

Note that these drugs are extremely similar, supporting the hypothesis that $NKTR's Dapi should be valued similarly to Lifti:
➡Both Dapi and Lifti are new MOAs for treating Lupus
➡Both drugs are in similar development timelines
      ↪$NKTR's Dapi actually already has P3 data available, versus only P2 data for $BIIB's Lifti
➡ Both drugs have shown very similar efficacy

Attached photos show
1⃣ A table comparing the existing Lupus data between these drugs (validating Dapi as a drug that can be fairly value-comped to Lifti)
2⃣ A screenshot from $NKTR's most recent 10Q that:
      ↪Details their royalty/milestone rights
      ↪Explicitly states that the value of this agreement has, to date, been omitted from the company's calculations

Also note that $NKTR already has a history of striking lucrative deals on drug royalties:
1⃣ A 2012 royalty deal with $RPRX for $124M
2⃣ A 2020 royalty deal with HRM for $150M
3⃣❓In my opinion, $NKTR now has excellent proof of concept to leverage their Dapirolizumab rights into a 3rd 9-figure royalty payout, as they have consistently executed similar deals in the past.

So, now $NKTR not only has 2x its market cap in cash, but arguably 1x its market cap in Dapirolizumab NPV.  At present, my opinion is that $NKTR would have to ~3x from today's opening price just to arrive at a ~$0 valuation for its atopic dermatitis shot on goal, which as my pitch highlights should be the PRIMARY value driver for the company!

As I will keep saying, there are ALWAYS huge risks in small cap biotech.  But, yesterday's new development for $NKTR officially pushes me to call this the best risk/reward skewed biotech setup I have ever seen.

---

Yet another positive development for $NKTR yesterday, as they announced that a 3rd party (TrialNet) is coming in to fund a P2 trial of their drug (Rezpeg) In Type 1 Diabetes.  This gives the company yet another shot on goal outside of atopic derm.  Best of all, it's a free shot on goal.

Honestly, I probably would've been critical of the company if they launched this on their own, as it would have been yet another source of cash burn.  But when someone offers to PAY to study your drug in another disease *without taking any rights to the drug or any profits/royalties from it if it ultimately works*...you say yes!  We are talking about a trial that will likely costs 10s of millions of dollars - paid for by TrialNet.  $NKTR just has to supply the drug...

~$155M cap at $0.84/share with ~$280M cash.  ➡~0.55x cash multiple
➡A promising P2 atopic derm readout in Q2
➡Dapirolizumab royalty stream (arguably worth nearly the entire current market cap on its own)
➡Alopecia areata readout after the AD readout
➡An externally fully funded shot on goal in type 1 diabetes without losing any rights to the drug

To me $NKTR still looks like the widest biotech mispricing I've ever seen.

---

Well June is upon us - $NKTR will report the AD data sometime this month (most likely late in the month IMO).  I definitely would have expected the stock to trade up more into the June timeline than this, but I suppose that it is up ~6% since my thesis was shared while the $XBI has been through a historic dip and is down ~12% over the same timespan.

The market clearly continues to think that there is very near zero chance that this trial hits.  Obviously my take from the P1 data is that the probability of success is meaningfully higher than zero, but of course there's risk of a complete whiff here.

Again, my take has never been "The $NKTR AD readout is very likely to be successful", but rather "The $NKTR AD readout's chances of success are nowhere near appropriately priced into the stock."

I definitely continue to believe that to be true.  This is one of those readouts where you can logically say "I don't think this trial is likely to hit" and *still* consider it a good long (for a rough example, 20% probability of 10x is a bet you should take every time you can get it, even though you think the most likely outcome for each iteration is failure).

Then of course we still have other moves like the Dapi royalty monetization potential, which I continue to see as highly valuable to the company.  This is the element that for me pushed this setup into the territory of "best I've seen".  I think the market continues to doubt the company's ability to pull off a good deal for Dapi, despite the fact that NKTR has done if before.  At the very least this could offer downside protection in the event of an AD readout failure, if not some upside otherwise.

As for me, I own far more $NKTR now than I did when I first shared my thesis.  It is definitely a very high risk/reward readout, and is not for the faint of heart.  If you're long and you think the AD readout is very high POS, take some time to consider how often this sort of thing blows up in small cap biotech.  The market is doubtful for a reason - there is no reward without risk!  This is one to be careful with.

Good luck to all!

P.S.  The company should shut down, monetize assets, and return cash to shareholders if this readout misses.

---

Lots of questions about $NKTR stock split.  First of all, if you’re freaked out, you should consider just following your gut and ditching it.  Biotech microcap shitco investing (gambling) is not for everyone.  RISKY!

What does the R/S before data mean for the POS of the AD readout?  Who knows.  This will be looked back on like going for a 2 point conversion at the end of a tied game:

If it misses, everyone will say “see, it was OBVIOUS this was going to miss after the R/S.”

If it hits, everyone will say “obviously they wanted to shrink the float and clean the balance sheet for financing before the successful readout!”

The fact of the matter is this reverse split plan was public information that was voted on back on May 23rd (yes, you could have already known this was coming for 2 weeks).

Personally I don’t think they had data available to analyze at that time, so I’m not falling into either of the 2 camps above.  Even if it hits I’m not going to claim I “knew success was coming”, because I don’t think they’ve got the data analyzed (as previously posted, late June is my suspicion for data release - May 23rd likely to early IMO).

The stock had been noncompliant with Nasdaq listing requirements for almost exactly 180 days as of the vote on May 23rd.  The timing makes total sense from that perspective.

Yes if they miss ultimately they will have *had* to do a split.  Yes if they hit the stock “squeeze” could be more volatile with a tighter float.  You guys can argue about which of those two narratives you prefer - Personally I don’t think they had the data back in May to inform this decision either way 🤷🏻♂

---

$NKTR data are finally coming tomorrow.  I continue to believe that essentially *any* stat sig hit on EASI75 should cause a *significant* rally for the stock.

It closed at $9.54 today, yielding a market cap of ~$106M with the new split-adjusted OS of 12.4M.  Most recent cash of ~$220M keeps the stock trading <0.5x cash into the data...The market has been saying that there is basically zero chance this thing is going to hit.

That sentiment (that this readout will obviously fail) is reflected in the after hours action of the stock tonight.  Simply because the company pre-announced the data readout for tomorrow morning, the stock traded +35% on what was actually quite a liquid move.

Why?  Because some people see the preannouncement as a slight signal that the readout might not actually be a flat out miss.  The fact that the stock *should* be up on any hit from these prices led to people piling in after hours just because of whatever mild probability of success adjustment the "data preannouncement" portends.  IMO, a move like this wouldn't happen if people felt that $NKTR could hit tomorrow and still not trade up a lot.

Jeffries recent analysis of the setup agrees with my opinion that almost any hit could cause the stock to rip, with up to 5x, or ~$50/share, potential for their worst case "hit" scenario (18-25% EASI75 delta, with <5x at the lower end of those bounds obviously).

I strongly agree that NKTR should rally big time from such low prices if they actually have a drug here.  $NKTR has a unique MOA plus strong rationale & POC data for potentially very sparse dosing (maybe even Q3M like $APGE, which sports a valuation >20x $NKTR's despite $APGE being at the same development stage and sporting a "me too" MOA... actually it would be the **4th** IL4/13 inhibitor to market...)

Even 20% EASI75 delta for $NKTR would be great in my opinion.  Look at the recent launch curve for Nemluvio, which had an awful 13% EASI75 delta in its P3 studies *and* worse NRI itch data than dupi/lebri.  Despite that, Nemluvio is launching as if it is going to be a clear blockbuster - likely mostly because it is a new MOA for AD and our options are currently very limited.

As a dermatologist myself:  We need new MOAs for atopic derm!  I have recently encountered a lot of people who seem to assume that IL4/13 is "enough" for atopic derm.  This could not be further from true!  Only ~50-60% of patients even meet the primary endpoint (EASI75) with IL4/13i to begin with.  Another 5-10% end up with conjunctivitis or the "paradoxical facial redness" AEs.  Now, increasingly since Dupi has been around for a while, we are often seeing patients who are losing response to dupi after having responded for years.  This is exactly what we see in psoriasis as well...Except, we have fewer drugs for atopic derm, currently only 2 biologic MOAs (IL4/13 and IL-31), and atopic derm is nearly 2x larger of a market than psoriasis!

The unmet need for new MOAs in atopic derm is huge, and somehow it seems like this issue has been widely underrecognized.  This likely explains why an AWFUL (imo) drug like nemluvio is launching like a rocket despite awful EASI75 delta and inferior itch data.  We just need new MOAs!

If $NKTR hits at all tomorrow, it will be a new/unique MOA and will have potential to be dosed more sparsely than anything else on the market (maybe Q3M for $NKTR - the sparsest right now is Lebri at Q4W).  That, IMO, would be a valuable/useful drug.

In the unlikely event that $NKTR actually shows Dupi/Lebri level efficacy with EASI75 delta >30%...well, look out - this thing would rocket.  Jeffries 15x projection yielding >$140/share could actually feasibly happen.  It's not often that a move like that is even in the cards, but I sincerely believe it's possible with the insanely cheap valuation coming into this and the market having written this off completely despite *huge* TAM and unmet need.  Again, $APGE with its "me-four" MOA and sparse dosing is currently trading at $2.5B...well over 20x $NKTR's cap today.  *If* NKTR looks IL4/13-level efficacious and can actually do sparser dosing, why should it be *cheaper* than $APGE with them both being at the same stage of development?

Anyway, I have no idea whether the preannouncement means anything or not.  I'm nervous.  It's a big position for me as I have put my money where my mouth is here.  Maybe it misses stat sig entirely and trades down ~50%.  If that's the case, oh well - If I could get this setup 100 times I'm confident that I'd come out on top in aggregate, making this a risk worth taking.

Good luck everyone - see you in the morning!

(Jeffries scenarios and Nemluvio/Eblgyss launch data below)

---

$NKTR that’s a hit!

Overall ~23.5% delta.

Low (mid) dose delta was 29% (!!!) which is absolutely a huge hit.  I wonder if this is the dose they’ll take forward - there is significant mechanistic rationale for reaching an inverse dose response with IL-2 drugs, so lower could actually be better here unlike most cases, and 29% is right in the range of “dupi like” activity.

This is an incredible result for how this stock was being priced/left for dead into data!

Today is going to get wild for $NKTR 😎

---

There’s probably nobody on the planet more biased than me about what $NKTR is worth right now, but I’m telling you if I had this drug in my clinic right now I’d be using it frequently.  Initial ~$25 price action seems like a significant underreaction to me.  That’s barely even a $100M EV for what absolutely looks like a viable drug (again, see Nemluvio launch curve with an EASI75 delta *half* of what $NKTR just showed).

The other wild card is the fact that now this has been *clearly* shown to be a viable drug, $NKTR’s chances of getting a major payout in the Eli Lilly lawsuit for the initial data analysis mistakes just went up exponentially.  $NKTR was eligible for up to $250M more in payments on that collaboration before Lilly discontinued it using the mistaken data to inform their decision.  And I’m certain $NKTR will argue for lost time/damages in the suit as well.  At this point, I like their odds of getting a substantial payout from that.

Oh, and they still haven’t even licensed their (likely 9 figure value) dapirolizumab royalty yet.

Tons of examples of ability to buy for way too cheap right after good data in biotech lately…heck, it even happened with $CDTX at $28 premarket yesterday…$48 now already.   Again, I’m biased but I think we *should* be seeing that here.

The valuation is so low, they still have a lot of cash, they’re likely to be coming into more, and this absolutely looks like a viable drug with a brand new MOA for a massive TAM.  <$100M EV for all of that?  Hmmm

---

Oh, and another note on $NKTR.

This makes their upcoming alopecia areata readout *MUCH* more interesting now that we know for sure this drug is active.  There are no biologics approved for that condition *at all*.   The data readout is only a few months away, and the upside if it works in that condition (even a little bit) would be significant.

This alopecia program was worth absolutely $0 NPV before today, but now it is a super interesting shot on goal.  If they hit there, it would be an obviously huge win, because there’s literally no safe injectable drug approved for the disease.  Time to start working on that readout!

Next few months for $NKTR are packed:
➡Dapirolizumab royalty?  💰
➡$LLY lawsuit settlement? 👨⚖⚖
➡Alopecia Areata P2 data? 👨🦲

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Eh, screw it.

Just bought more $NKTR on what I am considering a “dip” in the $21s-$23 range.  Too cheap imo 🤷🏻♂��

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And bought more $NKTR in the $17s 😂

---

I own more $NKTR today than I did yesterday, and I have yet to sell a *single* share.

Good luck and congrats to anyone who did well on this one - just know that the next stock I pitch is now guaranteed to go up in flames!

---

Here is a fun excerpt from my $NKTR pitch that encapsulates one of the reasons I think it has still not traded up enough.  Its enterprise value is still ~$100M...which puts it at less than half of the EV that $QTTB, $ANAB, and $CRVS all had *BEFORE* their atopic derm readouts.

Of course, $QTTB and $ANAB outright failed, whereas $NKTR succeeded!  Yet, being on the other side of success on a massive binary, the $NKTR valuation doesn't even reflect the valuation the market was willing to ascribe to two pre-data companies with unvalidated MOAs that had risk of total failure.  $NKTR doesn't have risk of failing in P2...they just hit!  Does this pricing make sense?

$NKTR's EV could pretty easily become *negative* again at these prices if they are able to out license the dapi royalty and or get a settlement out of $LLY...

Also, are we willing to assign some value to Rezpeg in the upcoming alopecia areata readout?  Their drug is CLEARLY active for T-cell mediated diseases of the skin.  Or do we only ascribe value to drugs with zero data in their respective indication and totally unproven MOAs? 🤷♂

---

$NKTR added ~$60M today in market cap…amazing how these tiny market caps can make “big moves” that are actually super small in terms of absolute valuation.

Enterprise value is *still* well below these what these other “comps” had BEFORE they went into their data.  No need to even complicate the valuation exercise beyond that simple observation at this point from my perspective.

---

Fully updated $NKTR pitch, including a separate new and in-depth google doc, available here!

https://t.co/04QkhWlXpF

---

$NKTR BVF filing

https://t.co/ENYtZv7VKC https://t.co/VgHYtbb064


Summary: Bullish SRRK: trial hit the pre-specified primary endpoint, clearing the key FDA approval hurdle; broad patient uptake expected.

$SRRK Imagine having a kid with SMA and not wanting to use this drug for them.

Effect size being big enough to hit the pre specified PE and get past the FDA approval is basically the only thing that mattered here.  Checked that box.

If you or your kid is on Spinraza you’re going to ask for apitegromab too.

... $SRRK data a bit weak effect wise, but will get broad usage, should be a good sized drug, i would buy


I'm in the process of building a $CYTK bag of my own now. I think they can turn it around

Summary: Actively buying CYTK, believes company can turn around.

@buckorama1 I’m in the process of building a $CYTK bag of my own now.  I think they can turn it around 🫡

Would’ve been better for them if they just sold in the first place though 😅

@A_May_MD Adam--wished that I heeded your advice re: $CYTK.  Signed.  Bagholder.


the only biotech whose insiders bought >$40M in stock at a massive premium to its current share price in the last week. I've never seen anything remotely like this.

Summary: Bullish TECX on unprecedented insider buying >$40M at premium; bearish XBI on broken biotech market conditions.

$TECX  Is the WORST performing biotech (>$300M cap) stock in the last week, and simultaneously the only biotech whose insiders bought >$40M in stock at a massive premium to its current share price in the last week.  I’ve never seen anything remotely like this.

$XBI  What could be more emblematic of how absolutely BROKEN the biotech market is right now?

@A_May_MD Fun fact

not only is TECX off a lot, it's the SINGLE WORST biotech >300M in the last week (>200 names)


Summary: Repeatedly buying SRRK whenever price starts with $3, algo triggered again; target close above $40.

My highly complex algo that leads to buying of $SRRK when its stock price begins with a 3 has been triggered yet again.

---

Aaand close over $40.  $SRRK 3xx algo remains undefeated.  Would be happy to chat with some AI and or quantitative experts about how I constructed this extremely nuanced algorithm.

---

Uh oh $SRRK

---

#Triggered

---

Close over $40.  Rinse and repeat.

---

$SRRK $3xx algo hits again.

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Holy crap
$SRRK #SRRK$3xxAlgo https://t.co/UbAPbuqACn


Summary: Bearish ACRS and QTTB: TSLP is not a viable MOA for atopic derm; ACRS data misleading, QTTB drug performed worse than placebo in blinded study.

Like I said, prepare to be shocked at how meaningless these $ACRS data are.  TSLP is not a viable MOA for atopic derm, and the TSLP lead they just brought in is very likely worthless.  $QTTB placebo arm just showed a 76% mean EASI reduction with their in their TSLP study, vs 74% reduction on drug (LMAO).  Worse than placebo.

$AZN’s TSLP tezepelumab failed in atopic derm before this.  The MOA doesn’t work, and even if it did, the AD SOC benchmarks are insanely high.

Who cares about $ACRS 90% mean EASI reduction in an open label, mild patient study when this $QTTB blinded study showed 76% mean EASI reduction on placebo with more severe patients?  Game over.

“Dupi killer”, my ass.

$ACRS $REGN $LLY

It’ll be a while before this is official but just prepare to be shocked at how misleading n=18, open label, baseline EASI=17.5 data are in atopic derm.

Good luck competing with Lebrikizumab 🫡


Summary: Endorses long PHVS; agrees low-popularity is a positive indicator for the stock.

@MBbiotech Totally agree!  And with you on $PHVS FWIW 😜

@A_May_MD Popularity on twitter is an inverse indicator. It's a strike against a stock, rather than something favorable. Biggest concern for VKTX, OCUL. Many uber popular stocks have crash and burn in the past. I'd cite PHVS as an example of a stock I like partly because its not popular


0 VOCs on $CRSP trial to date may suggest we're already there? … first to market matters a lot here

Summary: Bullish CRSP: zero VOCs suggests HbF threshold already met, and first-to-market advantage is significant given low expected demand constraining multi-player dynamics.

@Biotech2k1 More HbF will not be a differentiator past certain threshold. What that threshold actually is will be up for debate.

0 VOCs on $CRSP trial to date may suggest we’re already there?

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@Biotech2k1 And, personally, I think demand will be low enough for these treatments that multiple manufacturers gaining traction just because of supply constraints won’t be an issue.   If that believe is true, then first to market matters a lot here.


Goes to show just how unimpressive the clinical data actually are once you've looked under the hood. Added nothing to the company's valuation.

Summary: Bearish KYMR: SNY opt-in failed to add value; clinical data unimpressive and stock breaking below announcement-day price.

So despite $SNY opting in to the $KYMR program, the stock is *still* about to break below the price from the day of the announcement.

Goes to show just how unimpressive the clinical data actually are once you’ve looked under the hood. Added nothing to the company’s valuation.


I don't think $SRRK is going to be around for much longer

Summary: Bullish on SRRK (acquisition target), TARS, and VRNA as standout biotechs setting 52-week highs in a down week.

It was an absolutely horrendous week for biotech as many have pointed out, but I do happen to know of at least 3 biotechs that set new 52wk highs this very week.

$SRRK $TARS $VRNA 👀👀👀

Alright I swear I’m not going to make a habit out of this, but I’ve got to add $SRRK to the list.  I don’t think $SRRK is going to be around for much longer.

$VRNA $TARS $SRRK


Summary: Bearish AVXL: drug lacks FDA clearance to study Alzheimer's in the US; calls it obvious fraud.

I don't think the retail investors getting scammed into buying $AVXL BS realize the drug isn't even cleared to be studied in Alz in the United States (where drugs make money). FDA is pretty good at sniffing out fraud, so there's your reason.

I mean, even $SAVA has FDA clearance!

---

So to be long AVXL, you have to believe that a company has a legitimate drug for a massive indication, yet cannot be bothered to simply submit the paperwork for it to be studied in the most lucrative market in the world.

Spotting fraud can be tough, but sometimes it's obvious.


Summary: Bullish SRRK: high probability of significant lean mass signal in GLP-1 combo study; data expected mid-2025.

What's the bear thesis for $SRRK obesity study not working at this point after SMA POC?

I personally think that the probability of seeing a statistically significant signal for lean mass preservation in GLP-1 combo has become exceptionally high.

Data coming ~mid 2025.

$LLY starting their own Bimagrumab study in combo with tirzepatide. Perhaps there actually was a positive signal seen with Bima+Sema?

Most seem to have discounted the Bima+Sema trial as a fail; this Tirz+Bima trial is smaller + faster

$SRRK $BHVN $VERU

https://t.co/FqhwKvVbOA https://t.co/jGWTGPebLA


Summary: AMGN's MG-specific sales hires signal marketable MG data; bullish AMGN, bearish ARGX and IMVT as competitive pressure builds.

FDA approval is not the question at hand.  I agree, that’s usually what people are pumping “new hire news” for.  In those instances, the company has to work on hiring a sales force before FDA approval comes in so that they can launch immediately.  In those cases the hiring is not a true bull signal because they’re doing it regardless of approval or not.

$AMGN is not questioning FDA approval here.  The drug is approved already.  And now $AMGN has the MG data already.

6 weeks after the trial completes and all of a sudden $AMGN starts *specifically* adding myasthenia gravis hires to the existing salesforce of this drug.

Idk how anybody could see this as anything other than a sign that $AMGN thinks the MG data are marketable.

I also don’t see how anyone could claim that will have no potential effect on $ARGX and $IMVT.

@CloisterRes Agree with you. It takes time to interview candidates / find the right person so suspect they either wait until they unblind to send offer letter OR give offer contingent on data. Very common to hire a sales force for example with offer letter contingent on FDA approval.


Summary: Bullish RGNX: strong microdystrophin data and clean safety should draw investor attention following Sarepta's setback.

$RGNX with the random 9:15am PR going under the radar while we all focus on $IMVT this morning.

Very young patient with >100% microdystrophin increase.  Safety still sqeaky clean.  Program should be getting increased attention after yesterday's sad $SRPT news.
https://t.co/Z5P9MsFt5J


Summary: Long SRRK and IBIO on underappreciated myostatin/muscle-preservation approach that could deepen obesity drug weight loss beyond the ~23% ceiling.

$SRRK $IBIO $VERU $BHVN $KROS $REGN $LLY $NVO $VKTX $BIOA $AMGN

I think that $SRRK and $IBIO have an underappreciated opportunity to shake up the obesity landscape with their muscle-preserving myostatin approach. 💪

Some may argue that $SRRK & $IBIO are seeking to solve something that isn't a "problem", saying the 30-40% of weight lost on obesity drugs being muscle isn't certain to harm patients.  That's up for debate, though the case for showing functional improvement with muscle preservation (as $VERU data suggested in a very short 16 week study today), is a strong one in my opinion.

However, I am actually more interested in the idea that Muscle preservation could lead to deepening of the terminal weight loss curve.

A recent phenomenon in obesity studies has been that all programs, including those who pitched 25%+ weight loss, have found their weight loss efficacy bottoming out in the ~23% range.  Some studies may pass that range, but so far it is clear that companies have been surprised by how hard it is to drive weight loss past this ~20-23% zone.

This "bottoming out" phenomenon is especially odd when you consider that an "average" patient with a BMI of 38 on these studies losing an "average" 23% of their weight, still ends up with a BMI of~29 - on the high end of overweight and nearly still obese.  These patients clearly have more fat to lose, but their weight loss drugs suddenly stop working...How do we explain this?  Why would a patient who is still obese not be able to keep losing more weight on a GLP-1?

The best explanation I have seen is that the "sarcopenic" (low muscle) signal starts to override the satiety effects of the obesity drugs, making patients hungry again.  Basically, the idea is that your body is perfectly happy to keep burning more and more fat, since that is an "extra energy storage" tissue to begin with.  However, once your muscle reserves get sufficiently depleted, the body starts to get concerned and tells you "you have got to start eating again, I don't care what this weight loss drug says".

Most patients start obesity drugs with a huge fat:muscle ratio.  They have tons of "extra" fat, but usually very little "extra" muscle.  When you stop eating because of an obesity drug, you burn both relatively indiscriminately.

It seems possible that the reason obesity drugs are "bottoming out" in this 20-25% WL range despite the patients clearly have more weight to lose is that they lack the muscle reserves necessary to continue losing weight by caloric restriction alone.  Lose all your fat?  Fine.  Lose all your muscle?  NOT fine, and your body will step in to make you hungry again to prevent this.

To me, this is the big time upside case for $SRRK, $IBIO, and anyone else pursuing muscle preservation in obesity. I think that there is a real chance that these types of drugs could lead not only to "higher quality" weight loss (i.e. more fat loss, less muscle loss), but even more weight loss altogether in the long run.  There's even an argument that this sort of muscle-preserving weight loss could be more durable than the current GLP-1 weight loss that rebounds quickly once the drugs are stopped (with the thesis still being that the sarcopenia signal is telling patients that they need to be super hungry - eliminate this and they can keep the weight off).

The 20-25% terminal weight loss range has proven to be a difficult bar to pass, especially considering the GI tolerability issues that more intense WL regimens cause.  To me, this "sarcopenic override" hypothesis is the best explanation I have seen for this phenomenon.

Could $SRRK and $IBIO be onto a muscle preserving approach that leads to more fat loss, deeper overall weight loss, more tolerable weight loss, and weight loss that is more durable?  It may be counterintuitive, but I think there is strong (😉) rationale to suggest that "bulking" could lead to even more "shrinking" in the long run 💪

With $VERU getting crushed today, it seems to me that there is only one approach left in studies to address the "muscle loss" problem in obesity ➡Myostatin.

That leaves $SRRK and $IBIO as the only two public SMID cap companies I know of that are still in play.  Obviously I am


$LLY's choice of doses wasn't accidental…because when they dosed higher they ran into the same AE profile as $VKTX has! Obviously Lilly could have dosed higher if they wanted to but they're not idiotic enough to push the dose to where over half the patients are nauseas when they can achieve 20% WL without it.

Summary: Argues VKTX's higher-dose advantage is illusory — same AE profile forces tolerability tradeoffs LLY already solved; bearish VKTX, implicitly bullish LLY.

Uuuhh yeah $LLY’s choice of doses wasn’t accidental…because when they dosed higher they ran into the same AE profile as $VKTX has!  DUUUHH.  Obviously Lilly could have dosed higher if they wanted to but they’re not idiotic enough to push the dose to where over half the patients are nauseas when they can achieve 20% WL without it.

Also, wake up.  A SLOWER DOSE TITRATION THROUGH 13 WEEKS IS A LOWER DOSE OF THE DRUG THROUGH 13 WEEKS. You’re seriously going to sit there and try to tell me that giving fewer mg of the drug is not a lower dose?  Do you actually not have any idea how ridiculous you’re being?  Get a grip.  You’re off the rails.

@A_May_MD I compared the highest available doses for each drug. The fact that Viking can administer higher doses and achieve greater weight loss is a clear advantage. Lilly’s choice of doses wasn’t accidental, as I’m sure you’re aware. Also, I never claimed Viking would use lower doses; I


Summary: Bullish JANX: VIR data validates the platform beyond PSMA, no competing HER2 molecule, buyout or not 2025 looks hot for masked TCEs.

$VIR news is great for $JANX.  They don't have a competing HER2 molecule in the pipeline and this $VIR data is the validation $JANX needed to show that they're sitting on a legitimate platform here, not just a one-off shot with PSMA.

Buyout or not, I think it is looking like a hot year for these masked TCEs.

$VIR nice data thanks $SNY
$CTMX looks DOA per amgn
$JANX jpm buyout canceled ?


$REPL would be preferred in earlier (I.e. *larger*) populations than $IOVA's therapy would

Summary: Bullish REPL over IOVA: enrollment data shows doctors prefer REPL in larger earlier-line populations, relegating IOVA TILs to last resort.

This isn’t the flex you think it is.  It’s actually demonstrating the fact that doctors and patients would rather try $REPL therapy first.  Both $IOVA and $REPL studies had essentially the same enrollment criteria, yet $REPL enrolled much less refractory patients than $IOVA did.  This is a good demonstration of the fact that $REPL would be preferred in earlier (I.e. *larger*) populations than $IOVA’s therapy would.  Even in clinical trials people are saving $IOVA’s TILs for when *everything* else has already been exhausted.


Even in clinical trials people are saving $IOVA's TILs for when *everything* else has already been exhausted


$CGEM is half life extended so this specific issue won't be a problem. Longer half life, greater AUC with higher B cell depletion yet still lower CRS risk despite that greater efficacy. This may be the best case scenario for $CGEM

Summary: Long CGEM: half-life-extended CD19 TCE avoids CRS/AUC tradeoff vs short-half-life rivals, positioning it as best-in-class for SLE with no meaningful competition from blina-like agents.

$CGEM - Yes, very much so.  This agent with data above is low half life.  Because of that, you can’t push AUC without risking high Cmax, meaning high risk of CRS.  $CGEM is half life extended so this specific issue won’t be a problem.  Longer half life, greater AUC with higher B cell depletion yet still lower CRS risk despite that greater efficacy.

Blina (another short half life CD19 TCE) is not super effective for durable response in ALL either, unlike the half life extended CD20 and BCMA TCEs that produce CAR-T like responses and durability in NHL and MM respectively, which mimic the design of $CGEM’s TCE.

This may be the best case scenario for $CGEM if it means that super short half life TCEs like blina won’t be competition.

is the CD19 TCE thesis still alive in SLE?