Summary: Long TARS: blockbuster Xdemvy launch in demodex blepharitis, massive ocular rosacea opportunity underappreciated by market, ~$2B market cap looks cheap on combined TAM.

The presentation I am most interested in tomorrow is $TARS (which is a company sponsored call, not part of JPM).

I expect that they'll provide Q4 Xdemvy sales numbers in demodex blepharitis, which hopefully continue to impress in the first full year of sales.  This is one of a handful of biotech launches that have gone exceptionally well recently.  Aside from today (where the market was clearly bummed that $TARS wasn't bought out), the stock has been moving up nicely in step with their impressive launch.

Demodex blepharitis has been an underappreciated indication historically, but it is *big*, with millions of patients in the TAM.  Xdemvy is the first drug ever approved to treat the condition (which is essentially eye inflammation caused by mites that live in your skin and glands of your eyes - gross), and early KOL feedback is that ophthalmologists are diagnosing the condition more than they ever did before now that they actually have something to treat it with.  This suggests that the multi-million patient market could be even bigger than we already know.

As mentioned, the DB launch is going way better than analysts projected, and we'll see how Q4 lines up with those projections tomorrow.  Given how large the DB market likely is with its millions of addressable patients, $TARS may already have a blockbuster drug on its hands, potentially making the current ~$2B market cap look cheap on that opportunity alone.

However, where things get really interesting for $TARS to me is expansion into other indications, especially ocular rosacea.  This is a massive indication (over 15 million patients!) and one that is difficult to treat.

As a dermatologist, it is a frustrating condition because we are usually the ones who diagnose it (because patients come to derms for the rosacea rash on their face, often not realizing that the burning/itching in their eyes is the same condition) but we don't have good ways to treat it.  Patients are often put on long-term tetracycline antibiotics (sorry infectious disease docs) to control the condition, which can actually cause vision loss if untreated.  If we can't control it with antibiotics, its a referral to ophtho for other treatments.  But even for ophthalmologists - there are zero FDA approved drugs to treat this condition.

Personally I can say that if there were a highly efficacious FDA-approved topical treatment for ocular rosacea, I would try it in any rosacea patient with concurrent ocular symptoms consistent with ocular rosacea.  That would be a lot of patients, and I don't think many people are even factoring in the potential magnitude of a big-time derm launch for this company.

Clearly everyone slept on and underestimated the demodex blepharitis launch (as evidence by $TARS price action over this last year).  I personally think the same thing is likely to happen down the road with ocular rosacea.

It's early and rosacea/ocular rosacea trials are still ongoing, but if $TARS really is holding out for higher prices in buyout negotiations like the Betaville rumor says they are, I can see why.

If $TARS ends up with an ocular rosacea approval and it goes anything like this DB launch has, we are looking at blockbuster status for sure IMO, with a unique marketing overlap that involves both dermatologists ophthalmologists plus a nice mechanistic moat.  I personally think that the company is sitting on a great treatment for a couple of really underappreciated large markets.

As a fun aside, if you don't know what demodex mites are, check out the attached photos.  They are tiny bugs that live inside your pores, eating the oils that your glands produce (and yes, expelling their waste and offspring in there too).  In some cases they cause diseases like those that $TARS is treating.  Prevalence studies show super high rates of infestation with these mites among the general population, but I personally think prevalence studies are limited by sampling error and that absolutely EVERYONE has at least some of these guys living inside them.  Comforting, right?

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Dang, they aren't going to give us Q4 sales today.  Though they've said "blockbuster" about a dozen times in the first 5 minutes 😅


Summary: Author's own FY25 BBIO revenue estimate ~$206M sits far above ~$85M consensus, implying bullish outlook.

structural marker; pre-classified as canonical yfinance ticker

$BBIO Which row is for FY25 revenue?  The $316M line or $232M line?

I'm no expert on launch modelling but I built out FY25 with a series of (IMO) very conservative assumptions after the JPM 430 2024 Rx input and got ~$206M myself.

Way above the current ~$85M consensus.

Need more data on continued Rx trajectory and % of patients fully covered to get even remotely accurate though.

$BBIO I have not revisited Salim-Attruby model since it first published before launch - Salim definitely was bullish -but also point out not sure anyone understands or knows Attruby launch better then Salim -lots to digest here & ramifications going forward 3 phase 3 readouts https://t.co/EIsofExD1i


$JANX ~$40 … look like just silly risk/reward to me for 2025 … 30% below very recent offering price

Summary: Bullish JANX and VIR for 2025; both seen as deeply undervalued vs. their immuno-oncology platforms and recent data.

Also going on record here that $JANX ~$40 and $VIR ~$10 look like just silly risk/reward to me for 2025.  Relatively advanced, clearly active, widely applicable immune-oncology platforms...

➡$JANX 30% below very recent offering price.
➡$VIR with maybe the better platform going for ~$300M enterprise value?

Durability could still disappoint and derail them, but these seem like really skeptical valuations for what we have already seen in PSMA, EGFR, and HER2 datasets...


$VIR ~$10 look like just silly risk/reward to me for 2025 … maybe the better platform going for ~$300M enterprise value


$CGEM valuation does not make sense to me. You've got multiple pharmas paying more $$$ than $CGEM's entire enterprise value in order to partner on CD19 TCEs that are behind $CGEM in the clinic.

Summary: CGEM is undervalued — peers pay more to partner on inferior CD19 TCEs than CGEM's entire enterprise value.

"Yeah, we got a word for that kind of odd in Biotech.  It's called wrong."

You've got multiple pharmas paying more $$$ than $CGEM's entire enterprise value in order to partner on CD19 TCEs that are behind $CGEM in the clinic.

$CGEM valuation does not make sense to me.


Lilly is literally YEARS ahead of Viking on their own quadruple targeting program. Lilly's quad combo (Tirzepatide + Eloralintide -AKA LY3841136-) has already started a phase 2 combination study last month!

Summary: Debunks VKTX 'quad combo' narrative as pump/misinformation; LLY is years ahead with its own quad program already in Phase 2.

$VKTX $LLY $NVO $AMGN $PFE

More misleading narratives out here pumping $VKTX!  This time it is a shockingly stupid narrative about the supposed "quad combo" advantage on Fox News.

@semodough knows this is no offense to him but Fox (and anyone else pumping the quad combo narrative) is completely wrong about $VKTX having some "Quad Target" advantage.  This newest pump job is saying that Viking is trading up because they can do a quadruple target regimen versus Lilly's double (Tirzepatide) or triple (Retatrutide) regimens.

First off this is a pretty stupid way to frame the conversation to begin with ("Oh yeah, you can do 3 targets?!  Well then we will do FOUR!").  At this stage there's really no evidence to say that just tacking on extra targets makes anything better.  Alas, this stupid conversation is already rolling, so if we are going to have it we might as well get it right.

Lilly is literally YEARS ahead of Viking on their own quadruple targeting program.  Viking hasn't even named their Amylin/Calcitonin drug yet, and they aren't even filing an IND for it until next year.  The words "Amylin" and "Calcitonin" literally don't even show up a single time in Viking's newest corporate presentation from this month.  It will be years before Viking's Amylin/Aalcitonin drug is in combination studies for the "quad combo".

However, Lilly's quad combo (Tirzepatide + Eloralintide -AKA LY3841136-) has already started a phase 2 combination study last month!  (Here is the study if you are interested https://t.co/ipSmWOwZt6)

So again, people are being completely mislead about $VKTX and their position in the obesity landscape.  Not only does Lilly have their own "quad" program, but they are far, far ahead of Viking with it.

Be careful who you listen to on this stock!  Again, I'm not blaming @semodough here which I think he knows.  There's lots of garbage information coming from so called "analysts" out there to falsely inflate this stock's price, so you've really got to be careful trusting some of these narratives.

That is correct @FoxNews $LLY does not have Quad #Obesity like $VKTX IND filing for new dual amylin&calcitonin receptor agonist program in 2025, compound could rapidly advance to a combination with VK2735 to generate a “quad” (GLP-1, GIP, amylin, and calcitonin) regimen.


Could be looking at a drug with no anaphylaxis label, less frequent dosing, consistent effect across all types of urticaria, and markedly better efficacy. That would be a big time drug.

Summary: Bullish CLDX: early CSU data suggests most efficacious drug ever for the indication, 50% UAS7-0 vs Xolair 34%, favorable safety profile, and broad mechanistic rationale.

$CLDX Early small n data, but looks like this has a shot at being the most efficacious drug ever developed for CSU.

And unlike Xolair, there’s mechanistic rationale for use in all CSU patients (not to mention a large CIU population where Xolair barely works).

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They aren’t done dose escalating yet, but highest 2 dose levels combined produced UAS7-0 of 50%. Very favorable comp to Xolair P2 score of 34%.

Even more impressive when you consider that the $CLDX population contains many Xolair refractory patients.

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$CLDX multiple dose safety question does not seem to be an issue. “Neutropenia” signal does not look additive with repeat dosing, and ANC looks consistent with what was seen in the single dose CIU cohorts.

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Could be looking at a drug with no anaphylaxis label, less frequent dosing, consistent effect across all types of urticaria (not having to worry about urticaria-type diagnostic uncertainty is big), and markedly better efficacy.

That would be a big time drug.

$CLDX


Summary: CGEM is undervalued relative to comps/bidder interest; implied upside from M&A or rerating as US leader.

@jeromeleonard5 @BiotechObserver Yeah I mean that's what I'm saying too.  The value comps backed by multiple bidders say CGEM's valuation doesn't really make sense as a US leader in this space!

@BiotechObserver @A_May_MD He means for ex-china rights. $cgem isn't going to settle for less than 600-700m above cash either. Counting outstanding options, you likely get there even faster.


Summary: Predicts VKTX reaches triple-digit price tomorrow.


$RGNX has real tech and prospects... trading at almost HALF of cash... deeply negative EV considering the new cash infusions... the company at $7 /share would be trading at almost HALF of cash

Summary: Long RGNX: deeply negative EV (~-$200M) on $538M+ cash, Zolgensma royalties ~$80M/yr, and $562.5M in potential ABBV milestones make current $7 price irrational.

@avidresearch highlighted a great example of biotech market apathy (especially for gene therapy) yesterday.  $RGNX is a company with legitimate AAV technology, validated by existing on-market product ($NVS Zolgensma), high quality pharma partnerships ($ABBV collab), and a real (even if low POS) shot on goal in DMD.

On both Monday and Tuesday they announced updates that each confirm more cash coming in...yet they are trading down significantly on the week, literally hitting 52 week lows, now with a deeply negative EV considering the new cash infusions...

$278M Cash EO3Q24
$110M from new Partnership announced y'day
$150M from expected sale of PRV
--> $538M cash, a -$200M EV on their ~$340M cap.

This also doesn't take into account that on Monday they announced that they have official plans to start multiple P3s in their $ABBV collaboration.  First patient dosed in those trials will trigger a large payment as part of the overall $562.5M in development milestones that are included in that agreement (per @avidresearch the, $4/share cash from this P3 initiation milestone would be about ~$160M).  If this were included in current cash reservoirs as above, the company at $7 /share would be trading at almost HALF of cash...

This also doesn't take into account the fact that the company gets about $80M per year (ish) of Zolgensma royalties.

Yes, the company burns plenty of cash, so this has to be considered, but that degree negative EV is like the discount on some of these empty shell companies, while $RGNX has real tech and prospects.

This is a great example of how incredibly cynical the current biotech market is right now.  I'm interested to hear from people what other companies are looking similarly abandoned?

$RGNX $278M cash per last quarterly, plus $110M today plus PRV ~ $120M puts it at $10/share cash.

Will receive $4/share in cash from $ABBV (collaboration update provided yesterday) and more future milestones from $ABBV and Nippon.

Trading at $7 🤯


Summary: Predicts a share offering from TIL, implying dilution/downside pressure.

I was wrong the first time, but here’s round two.  Odd price action toward close.  $TIL offering coming 🔮

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https://t.co/6nx54e41yF


Summary: AMGN obesity drug disappoints on efficacy and tolerability; LLY and NVO implied beneficiaries.

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

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Yep that's what they said.  OK, not good.  $AMGN efficacy lower than expected and that tolerability sucks.  $LLY $NVO


Yep! The "down versus down" case is our culture and heritage. $XBI

Summary: Endorses bullish case for XBI biotech ETF.

@sciencescanner Yep!  The “down versus down” case is our culture and heritage.   $XBI

Me explaining the bull case for $XBI
#WhatIsDeadMayNeverDie https://t.co/vdrPDU1lsv


$CGEM is a subcutaneous injection that could potentially be given at home after an initial in office administration under observation (similar to Xolair). These are simple and scalable drugs.

Summary: Bullish on CGEM and ELYM as simple, scalable TCE drugs for I&I with CAR-T-like efficacy and superior safety/ease-of-use profile.

1.  It’s not rocket science man.  Look at the response rates in NHL and ALL and MM.   TCEs are *very* close to CAR-T efficacy.   Both modalities deplete B cells to complete levels of undetectability.  If the mechanism is the same and the response rates are close in oncology, why wouldn’t they be in I&I?  And while looking at the efficacy comparison, also look at sales.  Even in fatal cancers, people opt for TCEs at a significant rate due to safety and ease of use.  That same effect will be massively amplified in non-fatal mass market I&I.

2.  You don’t actually think AMGN is developing Blincyto in these indications do you?  Yes Blincyto is given via continuous infusion.  $CGEM is a subcutaneous injection that could potentially be given at home after an initial in office administration under observation (similar to Xolair).  $ELYM is just a standard mAb.  These are simple and scalable drugs.

3.  In vivo CAR-T is not currently a relevant modality, and will not be for the foreseeable future.  BTW, if you think that the secondary malignancy scare with current Auto-CAR-T is bad, imagine what it’s going to be like for in-vivo CAR-T where the construct is let loose in the periphery…

@A_May_MD Except no TCE has shown immune reset yet or durable response that compares with Schett. Will they be as potent as CAR-T is still VERY much an open question.  Schett has shown reset, Kyverna and Cabelta we do not know.  Kyverna likely not, Caba maybe, their SLE patient is still


Summary: Bearish BEAM; predicts it falls to $10 soon based on TECX-like trading pattern.

@adar170 Will be $10 soon if it trades like $TECX

$BEAM data out pm 38 bankers convince do offering 28 trading @ 24 now
this is biotech 2025


Valuation here is still minuscule. $IBIO should've been moving up for the last several months with multiple extremely positive fundamental developments... Making up for lost time now. I think if they can execute a strong financing after the NASDAQ uplisting (which is today) that it will do quite well

Summary: Long IBIO: minuscule valuation, positive fundamentals not yet priced in, NASDAQ uplisting catalyst plus pending financing should drive strong upside.

Yeah I do.  People often lose site of the actual valuation when these microcaps like $IBIO start making moves.  People will see a stock price double and bail, not considering that the actual valuation change was minimal.  Valuation here is still minuscule.

$IBIO should’ve been moving up for the last several months with multiple extremely positive fundamental developments, but it didn’t budge.  Making up for lost time now.

I think if they can execute a strong financing after the NASDAQ uplisting (which is today) that it will do quite well 🤞🏻

@A_May_MD Hey Adam do you still think $ibio has legs?


Summary: Bullish CRBP: CEO's paper suggests CB1 drugs lack true neuropsychiatric AE association, removing a key safety overhang.

@semodough The context is that the CEO of $CRBP published a paper this morning showing that there may not have actually been a real association between CB1 drugs and severe neuropsychiatric AEs to begin with, which obviously would be a good thing for CB1 if true.

https://t.co/RcUd5bB9rO

Thank you - so that’s basically the AE profile for $NVO Inversago CB1 receptor $NVO acquired


Summary: Long CGEM: long half-life CD19 TCE profile is necessary for I&I, positioning CGEM favorably vs short half-life competitors like Blincyto.

Also note an important point at the end of this Endpoints article made by $AZN EVP of Oncology R&D Susan Galbraith --> "I don’t think you get to the same level of exposure with [Blincyto] as we can achieve with this."   This echos a point I have been making on this front.   Short half-life TCEs will not be able to achieve significant drug exposures without forcing high Cmax, thus unacceptably increasing the risk of CRS/ICANS.

You need a long half-life drug like $CGEM's to have an ideal profile for a CD19 TCE in I&I.

https://t.co/EJlVFHDPkz

T cell engagers rule.  $JANX last week.  $AZN this week.

$AZN at ASH has updated oncology data for their CD3xCD19 T Cell engager (with important readthrough for $CGEM in autoimmune disease).

Now n=27 in FL, with 96% ORR & 85% CR.  This is shaping up to be highly competitive


$CGEM

Yep! And this may be a good explanation for why the early CD19 data suggest much more profound responses than we've seen with really any drug class ever in stuff like lupus

Summary: Bullish CGEM: early CD19 data show more profound responses than any prior drug class in lupus; T cell exhaustion thesis may add further efficacy advantage for TCEs.

$CGEM

Yep! And this may be a good explanation for why the early CD19 data suggest much more profound responses than we’ve seen with really any drug class ever in stuff like lupus (early data, we will see how it holds up).

Another pet theory of mine is that diseases with an obvious T cell component (RA and SLE both falling in that category) would actually benefit even more from a CD19 TCE than CD19 CAR-T.

Why?  Some people have pitched T cell exhaustion as a bear thesis for TCEs, saying they won’t work because T cells will get exhausted before killing all the B cells

I actually think that if T cell exhaustion occurs, it will be advantageous for TCEs in some diseases.  Basically if you use the T cells that are at disease sites causing pathology, and you exhaust those T cells in the process of using them to kill pathological B cells, you’ve just added to efficacy - you’re using up one problem cell to get rid of another.  And that’s adding efficacy in a way that CAR-T couldn’t.

All theoretical there.  We will see how it plays out!

@Anonym64382296 @MBbiotech @A_May_MD Not every disease is driven by just antibodies tho. So it matters for deep B cell depletion in addition to Antibodies.


Summary: Bullish TIL: even after +100% run, enterprise value is barely positive, implying further upside.

@adar170 $TIL And still barely positive enterprise value.


Summary: Bullish SRRK on obesity trial prospects; subgroup data consistent across age cohorts supports translation from SMA.

@Anonym64382296 Age differences are possible.  Interestingly SRRK subgroup analysis showed the same results in both the youngest and oldest cohorts.  I like their chances in obesity!

@A_May_MD Nice summary and I like SRRK. One reason the SMA data may not translate to obese adults is that the SMA patients are 2-21 years of age. Doesn’t mean it won’t translate, but that would be one possible outcome.


Summary: LLY Retatrutide will outperform AMGN MariTide on weight loss vs prior sellside expectations of a big gap; bullish LLY, bearish AMGN.

I mean...the $LLY TZP and $AMGN MariTide WL lines are overlapping.  Sellside was projecting a big gap (look at the stifel projection here).  I didn't hear a single person pitch this as equal efficacy to TZP.

$LLY Retatrutide is going to have greater WL than MariTide.


Summary: TIL can keep running; BNTX also bullish given same MOA as TIL and slightly ahead on development timeline vs SMMT comp.

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.

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$BNTX Roughly same dev stage - looks like they’re probably slightly ahead on timeline


$BNTX Roughly same dev stage - looks like they're probably slightly ahead on timeline


I like $VRNA and $TARS as buyout targets… the fact that I'm long both

Summary: Long both VRNA and TARS as potential buyout targets; author discloses held positions.

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 plays out 😅


Each day spent in the $30s is an affront to the natural order. The stock being red after today's numbers is an abomination.

Summary: Strongly bullish BBIO; trading in the $30s after today's numbers is unjustifiably cheap.

@MattBiotech Each day spent in the $30s is an affront to the natural order.  The stock being red after today’s numbers is an abomination.  This market should be ashamed of itself. https://t.co/Ml5zzFSM02

@A_May_MD Damn do I gotta buy $BBIO

But everyone’s doing it…


$HIMS is a high beta stock and as such should (and IMO will) be down much more than this

Summary: Bearish HIMS; expects it to fall significantly more as a high-beta stock, disagrees with bullish financial/growth outlook.

Drug Manufacturers - Specialty & Generic

@HighBetaBrendan Hi High Beta Brendan.  $HIMS is a high beta stock (seems like you should know this) and as such should (and IMO will) be down much more than this.

I also disagree on the rose-colored financial/growth outlook but imagine we will have to agree to disagree there.

@A_May_MD Hims trades at 20 times EV / FCF for 2026 estimates with a large part of revenue recurring. Those consensus estimates have no GLP-1s in them except personalized and liraglutide. I don’t see it as expensive rn. Management for the last 4 years has executed flawlessly IMO.


Summary: Bullish CGEM on AZN's CD3xCD19 TCE data showing CAR-T-level responses in oncology with strong autoimmune readthrough; also bullish AZN on impressive dataset.

T cell engagers rule.  $JANX last week.  $AZN this week.

$AZN at ASH has updated oncology data for their CD3xCD19 T Cell engager (with important readthrough for $CGEM in autoimmune disease).

Now n=27 in FL, with 96% ORR & 85% CR.  This is shaping up to be highly competitive with CAR-T response rates, despite using ZERO chemotherapy like the CAR-T regimens have to use.

New DLBCL data as well, n=19.  ORR 47% and CR 42%.  This would be a CR rate very slightly below conventional CAR-T at ~50%, however, what makes this whole dataset *Extremely* impressive is that many of these patients were already CAR-T refractory.

14 patients had already failed CAR-T therapy.  This population brings the response numbers down for the whole group, but there was still a 29% CR rate in the CAR-T r/r population.

So, spark notes --> CD3xCD19 TCEs are producing CAR-T level responses in oncology *despite* many of these patients having already failed CAR-T!  TCEs will be highly effective in autoimmune disease, generating "immune reset" at the same rate that CAR-T does, but without any chemotherapy.

https://t.co/EJlVFHDhv1

Part 3:  Bear point --> "But TCEs aren't as potent as CAR-T, so the efficacy won't be as good"

For starters, we are talking about treating I&I patients here, not *cancer* patients.  Patients who have B cell cancers with innumerable malignant B cells in their body are NOT the https://t.co/MvZStONKvV


$AZN at ASH has updated oncology data for their CD3xCD19 T Cell engager


Summary: Surprised by CRVS 50% drop given data that look encouraging; drug appears active, more cohort data upcoming could drive recovery.

A lot of really smart people were short $CRVS into yesterday's data.  I agreed, thinking the AD program was likely a dud (naturally I made nothing from this though because I couldn't stomach the risk of shorting something with such squeeze potential - lame🤦♂)

Ultimately though, I was surprised by how decent the $CRVS data looked, and thus perhaps even more surprised that the stock was down as much as 50%.

Maybe that move is fair, but I guess I'm just not really sure what the market would have needed to see from an n=16 dataset in a notoriously noisy indication for the data to have been received positively.  How could it have really looked much better?  Less placebo noise?  That's a lot to ask from an n=4 placebo arm!

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To me, the most useful information from the dataset is the (notoriously noisy!) mean EASI reduction.

At day 28, we can see that the $CRVS n=12 BID arm and the n=3 QD arm both appear to actually have deeper mean EASI reductions than dupi did in its SOLO1/2 studies. Taken at face value, this is extremely positive.  As always, caveats ahead (next "slide" in thread).

Important Notes:
- The $CRVS error bars really are quite tight.  Not much noise for such small n.  Especially in that n=3 200mg QD cohort.  For the error bars to be so small with such a small sample, all 3 patients must be responding similarly.  This is a suggestion of drug activity as opposed to noise.  Cohorts 1 and 2 following almost the exact same response trajectory also points in this direction.

-  The Dupi SOLO trials allowed rescue topical steroids to be used in patients not responding well, potentially making the results look stronger than true monotherapy would.  $CRVS did not have any treatment arm patients getting rescue topical steroids.

- The $CRVS treatment BID arm continues to have deepening response out to 8 weeks despite having no treatment from weeks 4-8.  Maybe this is noise.  However, there is biologic plausibility for "off drug" effect, since the ITK MOA is supposed to be affecting cell differentiation, not cytokines directly.  Efficacy via altering the effector cell population instead of via direct cytokine modulation could mean slower onset and offset of drug activity.  Such "remittive effect" is desirable in dermatology and has been seen with agents like tapinarof in psoriasis.

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The main complaint with the $CRVS data seems to be the placebo response.  Credit to @JNap5C for overlaying these trendlines.

From commentary, I gather that some people are concerned by day 15 data showing that placebo had deeper responses than the drug.  This is not overly concerning to me, as it is an extremely early timepoint that would never be a primary or secondary endpoint in an AD trial, and ultimately the placebo arm corrects to a much more reasonable response level of ~20-30% mean EASI reduction.

Aside from the discussion above about how the ITK MOA onset of action could be slower, surely we can appreciate that the day 15 50% placebo response is just noisy.  At all other timepoints assessed, the placebo arm doesn't crack even 30% EASI reduction.  Day 15 is the single outlier, and this is not surprising from a noisy endpoint with a miniscule n=4 sample size.

Yes, even at Day 28 the error bars overlap, thanks to the massive size of the placebo error bars (again -> NOISY endpoint).  But if people are really expecting stat sig mean EASI reductions by day 28 against an n=4 placebo arm, we need to adjust our expectations.  Have we already forgotten that $QTTB just showed a >75% mean EASI reduction on their large phase 2 placebo arm only last week?

Also, another very important note is that one of the placebo arm patients got rescue topical steroids for flaring, and that patient was not censured from the dataset.  So on top of the placebo sample size being very small, 1/4 of those patients got rescue treatment (versus ZERO patients on $CRVS treatment), likely artificially deepening the placebo response.  A 25% delta in the rescue therapy rate would be a very large difference in larger studies.  This likely influenced the placebo response depth in a meaningful way in the current $CRVS dataset.

There is  stat sig separation from placebo by day 58.  Is this just noise?  Maybe.  Or, maybe the proposed remittive MOA of $CRVS treatment is real, and patients can see continued benefit even after treatment stops.  Note that even at n=10 on day 58, those error bars are still VERY tight, suggesting that the effect is uniform across patients, potentially more likely to be drug effect than pure noise.

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At such small sample sizes, mean EASI is typically the best metric to use.  Threshold-based endpoints like EASI50/75 are even noisier.  Still, given that these will ultimately be the $CRVS regulatory endpoints, it is good to look at how they are trending.

So far, we can see that despite being assessed very early (week 8 for $CRVS as opposed to week 12 and week 16 for dupi comps), the Soquelitinib EASI response rates are shaping up quite nicely.  This was a big surprise to me.

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So, to summarize, the $CRVS data to me suggest their drug is active, and potentially meaningfully so.  This was surprising to me as I was a major skeptic heading into data and really just bearish on new MOAs in atopic dermatitis in general.

There's still a long way to go, and atopic derm placebo arms have gotten out of hand in some recent studies - the same could happen here.

Remember, my point is that the $CRVS data "aren't that bad".  I'm by no means saying we have a sure thing for AD here at all.  The bar is high and most have failed.

Still, overall I am surprised by how severe the $CRVS price reaction has been given my perspective that the data are generally encouraging, but we also have to consider the context of biotech/$XBI being in absolute meltdown mode right now.

Ultimately, data from the other cohorts isn't far off, and if it all shapes up like cohort 1 did, then I think $CRVS would get a lot of credit for potentially having a new, oral MOA for AD.


Summary: Bullish SRRK: if BHVN's SMA data is late (possibly failed), SRRK could have a blockbuster SMA product.

At what point do we consider the $BHVN SMA data to be “late”?  They completed enrollment in their study 5 days before $SRRK did, and their treatment period was *4 weeks shorter* than $SRRK’s.

So ostensibly if $BHVN analyzed data on the same timeline as $SRRK, they would’ve had data ready ~5 weeks ago, right?

$SRRK may have a blockbuster in SMA alone if $BHVN failed.

https://t.co/1V6mqAF1i6

https://t.co/XhxbcroANM


Summary: Bearish biotech ETFs XBI and IBB: rising rates from strong jobs data will further crush small-cap biotech.

Biotech is laying off as many people as it possibly can, but it isn't enough to prevent blowout jobs reports that launch rates and further crush small caps - especially biotech. $XBI $IBB https://t.co/fm21IJHYYP

Jobs Report smashes expectations, coming in at 256K vs 163K forecast. Yields surging to 4.78%, markets dropping.


Summary: Bullish NKTR: upcoming P2 data at 16 weeks (vs 12 in P1b) means more dosing time and potentially deeper efficacy vs comps.

Shorter trial, quicker and cheaper results.  Not abnormal to do this in earlier studies.  $NKTR data was P1b.  Comps in the tables are the bars set by larger P2 and P3 trials.

NKTRs upcoming P2 dataset will be at 16 weeks, which is 4 more weeks of dosing and potentially deeper efficacy.

@A_May_MD Why were the rezpeg data at week 12 instead of week 16 like the rest of comp?


Summary: Bullish SMMT: insider buying cited as a positive signal despite China-only trial concern.

@DarrenEstes @monaco_biotech I hear you.  At the same time, legitimate data *does* come out of China, and $SMMT insiders just bought a ton of stock.

@A_May_MD @monaco_biotech China only trial bothers me.


FDA approval should basically be considered a given. A lot seems to be going well for $SRRK in SMA right now

Summary: Long SRRK: FDA approval near-certain, first-to-market in SMA with clean safety + broad patient coverage; bearish BHVN (no POC, MOA concerns) and RHHBY (trial delays, strategic misstep excluding Spinraza patients).

$SRRK looks to have set itself up for being a legitimate revenue-producing biotech today.  IMO *FDA approval* should basically be considered a given.  A *lot* seems to be going well for $SRRK in SMA right now from my perspective.  An overview:

The regulatory bar is not particularly high in diseases like this (rare, fatal, genetic neuromuscular diseases).  SRRK clearly hit on the pre-specific primary endpoint and are trending positive in every secondary or subgroup where they didn't clearly hit stat sig.  On top of that the safety profile continues to be squeaky clean.  What argument does the FDA have to keep this off the market while patients are becoming progressively debilitated and/or dying from their disease?

The commercial bar is almost certainly even lower than the low regulatory bar. SMA patients are mostly children or young adults under the care of their parents.  What parent isn't going to do everything they can to get ahold of a drug that has *proven* it adds efficacy to the medicine they're already using?  FDA approves this, everyone is going to want to be on it.

---

$BHVN is seen as a potential competitor, but I personally don't think they're a big threat.  For one thing, everyone pairs $BHVN and $SRRK incorrectly as just "myostatin inhibitors".  SRRK targets the latent form of myostatin, whereas BHVN does not.  The idea that you have to target the latent form of the protein for the drug to work was foundational for SRRK - they've been beating that drum since they were formed years ago.

$SRRK actually had strong P2 proof of concept data too.  $BHVN has literally never presented in human efficacy data for their SMA program, unlike $SRRK that just hit in P3 after showing us a hit in P2 years ago.  Nothing from BHVN.

On top of that, $BHVN's P3 SMA study finished several weeks earlier than SRRK's did, yet we still have no data for it...hmm

BHVN has a different MOA (which most people don't realize), has never shown POC data, and appears to be late in disclosing the P3 results.  Doesn't seem very promising to me, especially when you consider that SRRK's effect size suggests that an even slightly inferior drug could easily fail.

---

$RHHBY is also cited as a competitor for $SRRK.  This is where I think things have *really* broken $SRRK's way.

For one thing, Roche's P3 SMA readout just got delayed (for some reason) from 2H24 to 2025.  Keep in mind this MANATEE trial is also a P2 (not a P3 like $SRRK) and we are only getting "part 1" data in 2025.  https://t.co/aHzUrUyWpu

So $SRRK is going to be first to market here by a pretty wide margin it seems.  That's a huge deal when patients are likely to get and stay on therapy for a lifetime.  It is still entirely possible that the Roche study fails, but even if it works and gets approved, $SRRK has a big lead to market here considering they were a $600M biotech going up against the behemoth Roche.

---

Finally, the biggest thing for $SRRK IMO.  $RHHBY didn't study their myostatin drug in combination with Spinraza!!!

The reason for this is clearly because Roche makes their own SMA drug, Evrysdi.  So obviously the ideal situation for them would be to make their Myostatin+Evrysdi combo the only option.  If nobody else hit with a myostatin drug, then spinraza patients would likely consider switching to everysdi so that they could get this proprietary combo.  That would've allowed Roche to not only get a new SMA drug on the market, but also grow their current SMA franchise.

However, now that $SRRK has hit in both Evrysdi and Spinraza patients, SRRK's drug can easily be used in all patients.  They'll get *all* of the Spinraza patients, and plenty of Evrysdi patients too given their first-to-market status.

Both Evrysdi and Spinraza are going to do >$1.5B in sales this year.  Roche swung for the fences by excluding spinraza patients from their trial.  $SRRK This has worked out exceptionally well for $SRRK.


Summary: Defends CRVS drug activity vs high placebo: drug response exceeds placebo, unlike QTTB where placebo exceeded drug; bearish QTTB, bullish CRVS.

What???

$QTTB’s placebo response was literally *higher* than the drug response at a mature timepoint.

$CRVS drug response is numerically quite a bit higher than placebo by a wide margin at only 4 weeks…

So, $QTTB placebo response is higher than drug…$CRVS placebo response is lower than drug…why exactly can’t I say that $QTTB placebo response killed $QTTB but not $CRVS? 🤔

Obviously there’s tons of noise, especially with a small placebo arm sample size of 4.

But to say that these $CRVS data suggest that their drug is inactive basically requires saying that $QTTB level placebo responses are the norm in atopic derm studies.  Wasn’t everyone just freaking out about how incredibly/abnormally high the $QTTB placebo response was literally less than a week ago?….

Which is it?

@A_May_MD @jesse_brodkin You can’t say PBO killed QTTB and not this. It killed both.


IOVA can't withstand any competition eroding their TAM at all. REPL threat is *much* more concerning with Amtagvi QoQ already flattening sub $50M

Summary: Bearish IOVA: unable to withstand competition, Amtagvi revenue already flattening, REPL threat is serious.

@STL_Biotech @JialiangLiang At this rate IOVA can’t withstand any competition eroding their TAM at all.  REPL threat is *much* more concerning with Amtagvi QoQ already flattening sub $50M

@JialiangLiang REPL is the closest one I've come to owning


Summary: Bullish SRRK: BIIB's higher-dose Spinraza data is good news for SRRK, which studied its drug with Spinraza, and strengthens the case for a BIIB buyout of SRRK.

Well this is again good news for $SRRK (and that $BIIB ➡ $SRRK buyout prediction some have posited may make even more sense).

Remember, $RHHBY didn’t study their myostatin drug with Spinraza (nusinersin) because they have their own SMA drug (Evrysdi) that they want to take more market share.

$SRRK did study their drug with Spinraza.  New $BIIB data are apparently showing that higher doses of Spinraza are better than those being used currently, likely making for even stronger “competition” against Roche’s Evrysdi, which has over time been “stealing” market share away from Spinraza.  Does the new high dose data have a chance at reversing or stabilizing that trend?

$BIIB announces detailed results from Part B and Part C of the Phase 2/3 DEVOTE study evaluating the safety and efficacy of an investigational higher dose regimen of nusinersen in spinal muscular atrophy (SMA). #WMS24

https://t.co/div9TFqzZ2


Viking having to go back to the drawing board and make new plans for a 6 to 9 month long phase 2b study would be an absolute disaster for the company... This is new a concern for Viking that I personally have not seen anyone discussing

Summary: Bearish VKTX: new FDA obesity guidance requires P2 trials to reach near-maximal weight loss, directly undermining Viking's claim to skip P2b; a forced re-run would delay phase 3 by over a year.

$VKTX $LLY $NVO $AMGN $GPCR $TERN $RHHBY $MRK $ZEAL $ALT
Newly updated FDA obesity draft guidance from yesterday introduces a potentially massive problem for Viking's VK2735 development plan.

Is $VKTX actually going to be able to go straight to phase 3 with SubQ VK2735, skipping P2b?

There is some interesting wording in the new FDA Obesity Draft Guidance (which was released just yesterday) that directly contradicts Viking's claims about being able to move straight into P3

Now, of course, this goes directly against what the company has been telling us about their ability to skip P2b, so I have gone back over the history of their discussion around this topic.  Let's review this below and then discuss the new FDA guidance after that:

➡2/27/24:  Viking first press releases 13 week P2 data for VK2735

➡4/24/24, 1Q24 EC:  The company is awaiting a Type C meeting with the FDA and is clearly still planning on running a p2b at this time, with the CEO saying "I think probably 6 or 9 months would be the 2 most likely candidates for duration of the P2b".

➡6/6/24, Jeffries Conference:  The type C meeting had still not occurred, however, this was the first time the company even mentioned P3 as a possible next step:  "whether that's a phase 2b or a phase 3".  So they were clearly thinking about this straight to phase 3 plan even before the Type C meeting.

➡7/24/24, 2Q24 EC:  The Type C meeting has occurred by this point.  "Based on written feedback from the agency, we intend to advance VK2735 into phase 3 development for obesity".

This call is also the first mention of an "End of phase 2" meeting being planned for the fourth quarter of 2024.

In the Q&A on this call, the CEO says (referring to the Type C meeting):  "One of the primary goals was to understand if we were okay to go forward into a P3.  And we *feel * based on the feedback that we got that we are okay to go forward."  Notice that these statements clearly suggest that the FDA did not overtly/explicitly tell Viking that they were OK to move into phase 3, but that the company just got that feeling from their feedback.

So, fast forward back to today - what's the problem with these statements now?   Viking's phase 2 study may not have been long enough to satisfy the FDAs requirements for moving into phase 3 studies.

The new FDA guidance from yesterday explicitly says:
 "The duration of phase 2 trials should be sufficient to capture the maximal or near maximal weight reduction effects of the active dosing regimens".

This is bad news for Viking, because they themselves have repeatedly said that their phase 2 study did not satisfy this requirement by saying "Weight loss in all treated cohorts appears to be progressive through 13 weeks and did not show evidence of plateauing."  That statement has appeared in numerous Viking press releases, including the one from just this morning.

Of course, we (and the FDA) don't need Viking to tell us this statement to know it is true.  Their existing phase 2 study would be by far the shortest ever conducted prior to entering phase 3 in obesity.

They only dosed the drug for 13 weeks in an n=175 study.  Compare this to Tirzepatide's P2 development program, which consisted of 2 studies:
  - NCT03311724 in n=111 for 12 weeks
  - NCT03131687 in n=318 for 26 weeks
So Lilly studied ~2.5x the sample size and for up to twice as long as Viking did.

By the updated FDA guidance from yesterday, even this 2x longer Lilly study from back in 2017 might not meet today's new standard for P2 obesity study length, which now according to the FDA must be long enough to reach "maximal or near maximal weight reduction".

Note that in P3, tirzepatide's weight loss was only ~15% at 26 weeks, and ultimately reached 22.5% at week 72 still technically without having shown a plateau (though the curve is getting quite flat at that point).  Assuming 15% weight loss at week 26, tirzepatide saw another 50% increase in the week 26 weight loss in order to arrive at the final 22.5% weight loss in week 72.  Does that qualify that "near" maximal efficacy?  I would say no.  So even this 26 week study of a drug with the same mechanism a VK2735 would not qualify for moving into phase 3 based on new standards.  Why should Viking be able to move to phase 3 with a study that was ***half*** that duration?

Interestingly, EVERYONE else but Viking seems to have already been on top of this problem, because current phase 2 obesity programs have almost entirely been designed to be even longer than the 26 week tirzepatide P2.
➡LLY Retatrutide Phase 2 is 48 weeks
➡AMGN MariTide Phase 2 is 52 weeks
➡PFE Danuglipron Phase 2 is 32 weeks
➡LLY Orforglipron Phase 2 is 36 weeks
➡NVO Cagrisema Phase 2 is 32 weeks
➡BO Survodutide Phase 2 is 46 weeks

This list goes on, but you get the point.  Other companies likely already knew based on FDA feedback that phase 2 trials should be long enough to get near maximal weight loss.  They were able to see that the original GLP1 P2 studies didn't even get close to maximal weight loss at 26 weeks, so everyone has been designing their studies to be even longer than that (which again, was already 2x longer than Viking's study).

Meanwhile, while everyone else is making their studies much longer than the 26 week tirzepatide studies, Viking has been telling us that they are going to be able to move forward with a study of half that duration...?

Everyone knows that 13 weeks is nowhere near enough to get close to maximum weight loss.  The idea that deeper weight loss will occur with longer studies has been a core bull thesis for $VKTX longs.  As noted above, the company's own official press releases allude to this fact, and the CEO has spoken to this multiple times.  For example, on the 9/4/24 MS conference where he said: "All of the curves appeared to be still downward at the 13 week endpoint, so it suggests that longer dosing windows could achieve greater weight loss".

Unfortunately for the company, that statement was bullish at the time that it was made, but yesterday's newly updated FDA guidance officially makes it so that these statements directly contradict the company's supposed ability to move straight into phase 3 with very short 13 week data.

In going through all of the available transcripts from all of the $VKTX calls that have been conducted since the P2 data were initially released in February of 2024, I have not been able to find a single example of the company explicitly saying that the FDA has already given them overt permission to move into phase 3 during the Type C meeting.  Their language has been much looser than that, with statements such as:
➡"we intend to advance VK2735 into phase 3" (2Q24 EC 7/24/24)
➡"we feel based on the feedback that we are okay to move forward" (2Q24 EC 7/24/24)
➡"the feedback we received indicates that it seems to be okay to go directly into a P3 study"  (MS 9/4/24)

This language makes it clear to me that the FDA has never given explicit permission to Viking for them move into phase 3, yet investors have largely taken this "straight to phase 3" plan as a done deal.  Now, add onto that the fact that we have yesterday's brand new FDA guidance explicitly telling us that P2 studies have to be long enough to reach "maximal or near maximal" weight loss, and suddenly Viking's brief 13 week study appears to clearly fall short of the FDA's official requirements for moving into phase 3.

Viking's end of phase 2 meeting was supposed to have happened already according to their guidance.  Has it?  Or has this meeting been delayed while the FDA awaited publication of these new guidance documents from yesterday.  Today's Viking PR about the oral program makes no mention either way.  The P2 data were available almost a year ago now (Feb 2024).  Why is it taking so long for Viking to start the phase 3?

Whether the end of phase 2 meeting has happened yet or not, what would make us think that the FDA is going to directly contradict their own brand new guidance by allowing Viking to move from a 13 week P2 study directly into P3?  Every other company is running phase 2 studies that are more than twice as long as Viking's existing P2.  There has to be a reason these companies run the studies for so long, right?
 Why would Viking be an exception to the FDA's rule?  What language could have been included in the Type C meeting feedback that made them "feel" like it "seems to be okay" to move straight into phase 2?  Would that language from mid year 2024 still be relevant today in light of the brand new FDA guidance from yesterday?

Given that the market seems to have taken the "straight to phase 3" claims at face value, Viking having to go back to the drawing board and make new plans for a 6 to 9 month long phase 2b study would be an absolute disaster for the company.  When including trial design/preparation, trial duration, and subsequent end of phase 2 meeting needs, this would cause well over a year long delay to current "time to market" projections.  This would be terrible for Viking's ability to take market share, especially given that it gets their potential launch so much closer to the end of semaglutide's patent life.

Personally, I don't now how likely this "disaster" actually is to occur.  The FDA can be unpredictable and even self-contradictory.  Given how confident the company has seemed about their straight-to-phase-3 plan, there may well have been some very clear language in their Type C meeting feedback that will make them an exception to the new P2 trial duration requirements and make them literally the only company that has ever gotten away with such a short trial duration.  It is entirely possible that they have the "all clear" from the FDA, and we will be hearing about their phase 3 trial launching in the first half of this year.  Frankly, knowing the FDA, this outcome would not surprise me at all.

Still, even if not surprising, it would seem odd to me that Viking could get away with a 13 week study while:
➡Everyone else  is currently running 32-52 week phase 2s
➡Yesterday's new FDA guidance clearly says P2s need to be long enough to get near maximal weight loss and yet:
     ↪Viking itself has repeatedly said in official documents and investors calls that their 13 week data did not suggest maximal weight loss
     ↪Even Lilly's original P2 tirzepatide study that was 2x longer than Viking's does not meet the new FDA guidance of reaching near maximal weight loss

This is new a concern for Viking that I personally have not seen anyone discussing.  I'm sure opinions will vary on how likely it is that we actually see the "disaster" scenario of needing to run a 2nd phase 2 study occur.  However, from my perspective, it is at least important to consider this potential problem as a legitimate brand new threat for Viking in spite of the fact that everyone seems to have taken the "Straight to phase 3" plan for granted.

---

JPM presentation has a slide that confirms EOP2 meeting occurred in Dec (consistent with sellside statements) and P3 studies still planned for 1H25. https://t.co/fjP103tJPS


I actually like $VIR PSMA data better. All about therapeutic window. There's looks likely to be wider than $JANX.

Summary: Bullish VIR over JANX on PSMA therapeutic window; author prefers VIR's data profile.

@avidresearch There’s a counter argument to this but I actually like $VIR PSMA data better.  All about therapeutic window.  There’s looks likely to be wider than $JANX. (In my opinion of course)

For some odd reason $VIR has not been able to catch a bid. While $JANX has the stronger PSMA data, $VIR data in very late stage HER2 was impressive enough to warrant credit (no competition). They are also on track to file IND for  EGFR drug this year. Good masked TCE.


Summary: Bullish IBIO at ~$2.85 PIPE price given MOA validation from SRRK hit and all competing ActIIRb approaches failing; also on record long SRRK with P2 obesity data due Q2.

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 on record for liking $SRRK, but haven't commented much on $IBIO.

I'm surprised you can still buy $IBIO around where their recent PIPE was done ($2.85) given all of the positive developments that have occurred since then:

➡$SRRK hit on function in SMA.  This is huge because this is the MOA of $IBIO's lead drug, and there were many doubters of this MOA before.
         ↪$SRRK traded up ~500% on this validation.  $IBIO is up only ~30%, which is a tiny move by market cap.  Why not more upside on proving a highly doubted MOA?
➡$BHVN failed in SMA with their ActIIRb targeting drug.  This is huge because this was the leading "competitive" MOA in the space, which was getting much more credit before myostatin hit.
➡$KROS also failed in their ActIIRb in obesity, not just in SMA like $BHVN.
➡$BHVN & $KROS have negative readthrough to $LLY's muscle/obesity approach, as they paid up to $1.9B for the Versanis ActIIRb pipeline in 2023.
➡$BIOA also failed in their muscle preserving obesity approach.

So, not only has $SRRK validated $IBIO's MOA that almost everyone expected to fail (on functional endpoints, no less!), but every other competitive approach that I'm aware has since failed.  Schwab still has $IBIO at a ~$28M valuation (though this does not account for warrants from the PIPE), and $SRRK P2 obesity data with their MOA is right around the corner in Q2.

This low valuation and lack of response to positive developments for $IBIO really doesn't make sense to me, especially given the significant attention and value that muscle-preservation approaches like ActIIRb got before they started failing (and before $SRRK showed myostatin succeeding!).

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


The $AVXL story has gotten as positive as it's going to get. The spin job is already running out of steam.

Summary: Bearish AVXL: claims the positive narrative has peaked and the spin is losing momentum, implying downside from here.

@MattNachtrab @Pogo881 There is not a company in the world that would hide a shred of positive data in Alzheimer’s disease. The $AVXL story has gotten as positive as it’s going to get. The spin job is already running out of steam.

@Pogo881 I’d say I’m slightly negatively biased on $avxl but it would be amazing if they released more information around this trial to allow a full evaluation of the significant improvement they claim. For now I’d lean toward lecanemab or $sava


Summary: Long CGEM: EV <$200M is a significant mispricing given CD19 TCE lead in I&I, zero CRS, massive TAM, pharma M&A comps, and positive lupus data expected in 2025.

I have never pinned anything on X, but I am going to keep this thread calling out  $CGEM as being undervalued pinned for a while, because I am feeling pretty confident about it.  I want to call my shot on this one.  The thread isn't short, but I hope it does a good job of documenting the general basis for what I think is a significant mispricing of Cullinan.

In the $15s right now, the market cap is under a billion, and the EV is <$200M with their surprisingly strong balance sheet.

Maybe there is some value in their oncology assets (they did get some good $ for half of zipalertinib ownership), but personally I am writing those off completely and focusing on CLN-978, their CD3xCD19 T-Cell Engager for I&I.

---

Part 1:  The Foundational Data.

The CD19 I&I hype really started with a small cohort of patients from Georg Schett.  This showed impressive efficacy of CD-19 CAR-T in 15 patients with Lupus, Inflammatory Myositis, and Systemic Sclerosis.

The most impressive data was from the Lupus patients, who universally went from severe disease that was refractory to essentially all available treatments to having no disease activity and no need for continuing medications after the CAR-T infusion.

This got a lot of people excited, as it looks like some patients have been *cured* of their lupus.  Given how severe their disease was and how poor the standard of care is even for less severe cases of Lupus, these results were truly remarkable.

Since then, several other small studies of CD19 CAR-T in multiple different I&I conditions have been published showing similar, sometimes curative-appearing results (won't discuss all of these for the sake of brevity, but there's a lot going on in this space).

https://t.co/5B1GC5BCKJ

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Part 2:  CAR-T has I&I POC - So why not just use CAR-T?  Why would you need $CGEM's TCE?

The simplest answer is that it is flat-out not possible to scale current CAR-T technologies to the massive markets in I&I indications.  Sure, maybe it could scale profitably for a few thousand of the most severe patients in the world, but we are talking about indications with hundreds of thousands to millions of patients.  Conventional CAR-T can't address a fraction of that.  Take $JNJ's Carvykti as a case study.  The demand for the drug is greater than they can supply and has been for years despite efforts to scale up.  They are losing out on money because they literally can't make enough doses.  Yet, if you back out how many patients are being dosed based on Carvytki revenues, it is only a few thousand patients per year at most.  This is not a reasonable modality for large I&I markets

$CGEM's TCE, however, uses an antibody modality that can easily scale to I&I mass market demand.

Scalability is just the simplest answer though.  Other drawbacks of CAR-T include dangerous and unpleasant lymphodepletion (chemotherapy) requirements, as well as the outstanding question of the long-term cancer risk associated with current lentivirus-based CAR-T programs.  These are not suitable for mass market I&I conditions. TCE's like $CGEM's would not have these problems.

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Part 3:  Bear point --> "But TCEs aren't as potent as CAR-T, so the efficacy won't be as good"

For starters, we are talking about treating I&I patients here, not *cancer* patients.  Patients who have B cell cancers with innumerable malignant B cells in their body are NOT the same as I&I patients who have normal (to sometimes even lymphopenic) B cell counts.  There is a very strong case to be made here that CAR-T is massive overkill in I&I, unlike in oncology where making sure that you kill every single B cell is literally a life or death pursuit.

Such high intensity is unlikely to be necessary in I&I where there are not only dramatically fewer B cells, but also B cells that are behaving more "normally" (not being driven by mutations favoring survival/proliferation).

Looking past the that fact maximum potency isn't necessary...TCEs are still incredibly potent anyway...  We can see this by comparing oncology datasets.

Take a look at AZN's CD19xCD3 TCE, TNB-486.  In an early Follicular Lymphoma dataset, it produced 7/8 (88%) complete responses.  This looks competitive with approved CAR-T FL efficacy with similar 70-80% CR rates.

CD19, CD20, and BCMA TCEs have all shown the ability to drive long term, durable, complete responses in patients with B cell cancers, meaning they have killed every last malignant B cell in the body.  Of course TCEs are potent enough to do the same thing in I&I patients who have a MUCH lower disease burden.

I have also seen some people claim that CD19 TCEs don't penetrate the tissue enough to deplete B cells like CAR-T does.  This is just silly, as the lymphomas that CD19 T cells treat involve bulky tissue-based disease.  Check out $CGEM's own oncology data where a 7cm tumor deposited inside of a patient's jaw bone gets completely eliminated by CLN-978 (photo below).

https://t.co/VRCu9u6G1Y

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Part 4:  Bear Point ->  CD20 TCEs will be good enough, and will beat CD19 TCEs to the market.

Just from a basic science perspective I think this is wrong.  CD20 is not expressed heavily on plasmablasts, which are likely the long-lived cell type that needs to be targeted for I&I.  CD20-/CD19+ cells are common and likely to be pathological.

On top of that basic science rationale, just look at the history of rituximab (CD20 mAb) in I&I conditions.  Rituxan has been used in many B cell mediated I&I conditions for over a decade, with universally mediocre results.  If Rituxan had the "curative" potential that we have seen with CD19 CAR-T, we would at least see the occasional "miraculous" or "cure-like" responder with rituxan therapy in the few patients who get really deep cell depletion with it.  If you can find a case report of a severe lupus/SSC/MG/RA/etc patient getting a cycle of rituxan and never needing treatment again, I'd love to see it (I don't think such cases exist).

If Rituxan/CD20 were truly targeting the underlying pathology (as I believe CD19 is), you would see a bell curve of responses that shows at least a few really remarkable responders out of the thousands of patients who have been treated with it.  But you don't.

I do believe that CD20 TCEs will be better than Rituxan due to deeper depletion, but they won't show the same magnitude of overwhelming efficacy we have seen from CD19 approaches so far.  The basic science and Rituxan POC both support the idea that hitting CD19+/CD20- cells is important.

---

Part 5:  Bear Point -> BCMA TCEs are already on the market and will work in I&I, we don't need CD19 TCEs.

This is a weak one so I'm not even going to spend much time on it.  BCMA is not safe enough for mass market I&I, period.  This approach made some waves with 2 recent NEJM publications using Teclistamab in I&I.

5 patients have been treated so far, and there are already 2 events of G2 CRS despite using tocilizumab and prophylactic steroids.  4/5 patients got infections.  2 out of those 4 patients got multiple infections.  CRS and infection risk are already known to be higher with BCMA CAR-T than CD19 CAR-T in oncology, and the early I&I data reinforce that.  These are dangerous events that will not be tolerated in I&I mass markets.

Given that the lupus POC we have with CD19 already shows curative-looking results, what's the benefit of using a more dangerous/immune suppressive target?  There isn't even any more efficacy to squeeze out here...

https://t.co/grXC5sKWsM
https://t.co/3QalG6IFvm

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Part 6:  Bear Point -> Speaking of CRS, CD19 TCEs are going to show that in I&I patients!

Low grade cytokine release syndrome will likely be a rare event in CD19 TCE I&I studies, sure.  But G1 CRS is just a low grade fever - a perfectly acceptable AE, even for at-home administered drugs.  Also, even this hasn't happened yet.

I am confident that CRS will be much much lower than in oncology applications.  Why?  Because CRS is directly correlated with the magnitude of T cell engagement, which is primarily a function of disease and T cell burden.  B cell cancer patients have orders of magnitude more B cells than I&I patients.  The cancer patients are literally overrun with millions of diseased B cells, whereas I&I patients will typically have normal to low B cell counts, which means that the T cell overactivation that drives CRS in oncology patients is unlikely to happen in I&I patients.

But don't take my word for it, just look at the fact that we haven't seen a single case of CRS in any CD19 TCE I&I patients so far.  I have data for 7 patients treated with blinatumomab and 6 patients treated with A-319.  Not a single case of CRS of any grade.

Now compare that to CAR-T in I&I, which re-introduces the risk of T cell overactivation (despite lower target burden), because you are literally infusion hundreds of millions of new T cells into the patient all at once.  In the seminal Schett paper we discussed above, 11/15 patients experienced CRS, including a single grade 2 case.

Meanwhile, 13 CD19 TCE patients treated so far, and not a single CRS case.

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Part 7:  Bear point -> What about CD19 mAbs?

Simply put, they're not going to be as efficacious as TCEs.  The depth of suppression in the tissues is not going to be enough to compete.  There is limited CD19 mAb data in oncology (partially because they were not efficacious enough to merit further study), but what data we do have clearly shows that CD19 mAbs are not capable of accomplishing total body CD19 B cell depletion at the rates that TCEs and CAR-T are.

Although I think the oncology POC data is strong enough alone to cement this opinion, the early comps we have between CD19 TCE and CD19 mAb in SSc support this thesis as well.

This is not to say CD19 mAbs won't have a role in I&I.  They will, and in fact already do with Uplizna.  These markets in I&I are huge and have room for multiple CD19 approaches, but my stance is that CD19 TCE will ultimately be the best.

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Part 8:  Bear point ->  The N=6 Blinatumomab RA study showed patients relapsing after 12 weeks!  Not good!

This is a bear point I have seen a lot, and I have to say bluntly that I find it to be very stupid.

First of all, these were patients who had failed *everything* for RA.  Median of 7 prior treatments, patients who had failed multiple JAK inhibitors.  As severe as it gets.

After only 2 doses of Blincyto, 100% of these patients had their disease go into "complete response" (as measured by DAS28-CRP).  These patients stayed in complete response with no further treatment until 12 weeks out (after which abatacept was started as symptoms started to return).  A drug that causes 3 months of remission after being dosed in 100% of the most severe RA patients who have failed all other treatments would be an incredibly desirable drug.  To call these results unimpressive because the patients weren't cured forever is asinine.

On top of that, the doses used in this RA POC study were very small.  They used 2 cycles of the priming dose of blina that is used for oncology patients (9ug/d versus 28ug/day).  And in oncology, patients get
many more than just 2 cycles, on top of the ~3x higher dose.

So this study showed 2 tiny doses of an old, short half life CD19 TCE creating 3 months of complete response in 100% of the most refractory RA population you can find...If this isn't positive proof of concept, then I don't know what is.

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Part 8:  On top of the growing body of CAR-T proof of concept, we already have POC data for CD19 TCEs in RA (above), SSc, and Lupus!

The response data we have so far from all of these early studies is extremely impressive, and would be more efficacious than any treatments currently approved in any of those conditions.  And again, zero cases of CRS across all of them!

Here are links to the available data so far:
SSc case --> https://t.co/J6aoab4HjP
RA cases --> https://t.co/Go88eAs4xS
Lupus cases -->
https://t.co/JwGNIo0BN7

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Part 9:  The markets are massive and $CGEM is in the lead!

We are literally talking about millions of patients with B-cell mediated I&I conditions that could be addressed by CD19 therapies (many of these conditions that already have proof of concept data as discussed above).

In this era of target-crowding there will be many companies pursuing CD19 TCEs given how encouraging the data above look.  However, impressively, CGEM is in the lead in this space despite the fact that they are a tiny biotech going up against numerous large pharma companies (they had the first IND cleared for half-life extended CD19 TCE in I&I in the US).  This is a rarity in this day and age, where it is usually the tiny biotech playing catch-up with a me too - especially when the market opportunity is potentially so large.

https://t.co/D67SJVpaz3

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Part 10:  Pharma is interested, and they are playing catch up.

$MRK just bought CN201, a CD19xCD3 TCE from Curon for $700M cash plus up to $600M in milestones.

$GSK just bought CMG1A46, a CD19xCD20xCD3 TCE from Chimagen for $300M cash  plus up to $550M in milestones.

Both of these drugs have only been studied in China.  Neither has cleared a US I&I IND like $CGEM's CLN-978 does.  They are behind $CGEM, yet the upfront cash alone for each of these deals is much greater than $CGEM's entire ~$200M enterprise value.

The fact that $CGEM is so cheap is validated by these deals, especially given the fact that they are ahead in US studies.  I do not expect this obvious valuation discrepancy to last forever.

https://t.co/DpGcRoitSe
https://t.co/6d3F6p7jas

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Part 11:  Valuation comments

So with all this strong POC showing great efficacy, zero CRS, massive total addressable markets, obvious pharma industry interest, superior scalability to CAR-T, and the very rare scenario of a small biotech being in the lead against big pharma on a promising new target, $CGEM still has very little value.  Why?

To be totally honest, I don't really know.  The fact that this looks so obviously cheap to me is why I am writing and pinning this long thread.  One explanation can certainly be the catalyst desert that $CGEM is in.  We will be getting data in lupus next year, but throughout the entire second half of 2024 there has been absolutely nothing for the stock to move up on other than occasional small studies of other CD19 compounds.  Short interest has gotten quite high as well.  I think in early 2025 as data starts approaching, shorts will ease off and the price will recover as people look forward to what is very likely to be positive lupus data.

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Part 12:  Bonus prediction

It is extremely stupid to say things like "the probability of specific company X buying specific company Y is xx.x%"

Predicting M&A at all is insanely hard, let alone correctly calling the company who is going to be the buyer.

With that said, and just for fun, I think $LLY buying $CGEM sometime after positive Lupus POC data makes a lot of sense.  As we have discussed above, other pharmas are already paying up for CD19 TCEs that are behind $CGEM, and this transaction would fit $LLY's MO of paying relatively big money for relatively early stage assets that are highly differentiated from existing SOCs ($DICE, $MORF, etc).  Again, very low probability of that happening, but I'm claiming style points if it does!


Summary: Bullish REPL on blowout clinical data: 36% ORR / 20% CR in melanoma beats all benchmarks with minimal toxicity; durable positive read.

Massive numbers from $REPL just now. 36% ORR and 20% CR in 75 PD1 r/r melanoma patients. Beats any benchmark you can find. Huge increase in response rate with minimal toxicity burden.

Oncolytic viruses are back!


Summary: Bullish CGEM: ~$100M EV with >$600M cash and sole CD19 TCE in US human trials while peers say entry costs $600-700M.

$CGEM with a ~$100M EV (>$600M in cash) while being literally the only CD19 TCE in US human clinical trials right now watching other companies say they would have to pay $600-$700M to get their hands on a CD19 TCE https://t.co/c6WtrJQdsx

Roivant comments on CD19 bispecifics. $CLYM $CGEM

"Costs 600-700m to get in the game". crowded field with lots of competition. https://t.co/AbZwZJjgdX


They will be sued into oblivion if they try to build a glp1 business off of this. I could list a dozen reasons why this personalized dose glp1 pitch is bullshit

Summary: Bearish HIMS: personalized GLP-1 dosing strategy is legally untenable at scale, company faces litigation risk and cannot build a GLP-1 business on this basis.

$HIMS Those “exceptions” are for an extremely narrow set of circumstances.  This “personalized dosing” thing is not an option at any meaningful scale, period.  They will be sued into oblivion if they try to build a glp1 business off of this.

Good luck getting doctors to widely prescribe random doses of glp1 that haven’t been studied too BTW.  There’s no reason to take on that kind of liability.

I could list a dozen reasons why this personalized dose glp1 pitch is bullshit, but let’s keep it simple:

$HIMS offered compounded tirzepatide until its shortage was declared over several months ago.  They no longer offer this drug at all.  Not in standard dosing.  Not in “personalized” dosing.  Why aren’t they selling personalized doses of tirzepatide?  It’s clearly the superior drug to semaglutide.  They aren’t doing it because it’s actually NOT LEGAL.

If this personalized dosing thing were really an option at scale, they’d be doing it already.  They aren’t.  It is not an option.

@NPjpk @A_May_MD I largely agree though, I think there's a couple of exceptions that should qualify under 503a.

But I don't think that's angle that Hims is going to test here.

I don't think this challenge is going to be as successful as Dudum anticipates. https://t.co/c99OUnAP0r


Misguided selloff of $CGEM in my opinion. CAR-T efficacy dropping below 100% is Goldilocks for non-cell-therapy I&I assets.

Summary: Bullish CGEM: CAR-T's sub-100% response rate is a bull thesis for TCEs/CD19 mAbs; selloff is misguided and the gap vs. standard of care remains massive.

Yes, exactly.  CAR-T having a high but not 100% response rate is precisely the bull thesis for $CGEM.  If CAR-T cures 100% of patients, then you can at least make the argument that it *might* be worth the manufacturing, cost, and burden of lymphodepletion in order to get a guaranteed cure.  If CAR-T is not a cure for all patients, that argument is much harder to make.  That’s where TCEs and CD19 mAbs come in.

Even if TCEs are slightly less efficacious than CAR-T, the gap between that level of efficacy versus the current standard of care in these conditions is still *massive*.  Both Blincyto and CAR-T have shown responses at rates that would be unprecedented with *any* other therapy and across numerous different conditions.   I mean, Benlysta didn’t even hit its primary endpoint in SLE and it’s doing >$1B/year in that indication alone!  There’s plenty of room for us to see significantly worse efficacy from CD19 drugs than early data suggest and still be able to say that these are the best treatments ever developed for some of these conditions.

CAR-T efficacy dropping below 100% is Goldilocks for non-cell-therapy I&I assets.  Now we can see that CAR-T is not a panacea and thus likely not worth the extra burdens it brings over antibody-based approaches that also yield 100% B cell/plasmablast depletion.  At this rate the data still suggest that CD19-based therapies in general may be better than any other existing options (to be proven by more trials but that’s the thesis supported by early data).

Misguided selloff of $CGEM in my opinion.

So even the CD19  TCE companies like $CGEM sold off on this CD19 CAR-T data? Bit confused, isn’t that actually bullish for them (TCEs can be repeat dosed etc)?


Summary: Bullish ELYM and CGEM on RA being a larger long-run opportunity than MG, with durable remission data eliminating APCA antibodies.

Fair counter with open label limitation, but are these really the response kinetics of a pure placebo response?  If it is all placebo, why were there 5 MG-ADL measurements taken before the score got down to zero?  And then how did it stay at zero out to 150 days (and counting)?   All placebo?

MG-ADL measures mundane/menial physical activities like standing, brushing your teeth, and literally breathing.  In the article they say that this patient is now jogging for >1 hour...

Doesn't sound to me like she just "mind over mattered" her MG away to that extent.  Looks a lot more like disease modification in a way that MG-ADL wouldn't even come close to measuring.

---

Also I get that MG is in focus right now because the Uplinza readout is likely impending, but jokes aside, isn't RA going to be the bigger deal in the long run?  Market is way bigger, and hard to argue that there is a gimicky MOA there given that this paper shows APCA Abs were actually eliminated along with the patient's durable RA remission.

Should be a bigger deal for $ELYM and $CGEM at least.  MG readthrough is maybe more important to FcRn companies if that's what this is all about.
https://t.co/TnVJvPAp2w


Summary: Bullish SRRK; myostatin-obesity data coming sooner than expected, catalyst ahead.

@adar170 Myostatin for obesity is about to be back in vogue.  $SRRK obesity data are coming sooner than people probably think!

$srrk
Now that obesity out of vogue clutch for them to hit sma


Summary: Bullish CGEM on strategic pivot to I&I (cutting oncology, expanding into RA with CLN-619) aligning with market preferences.

$CGEM seemingly getting the memo about what the market wants to see.
Cutting oncology drugs and expanding I&I.

Taking CLN-619 into the largest I&I indication with CD19 POC - rheumatoid arthritis.

Cullinan Therapeutics Provides Corporate Update and Reports Second Quarter 2024 Financial Results $CGEM https://t.co/v8iYVdCnSO


Summary: Bullish DRUG: author finds the red price action illogical given a 3-way bidding war for LBPH that drove its melt-up.

So we just learned a few minutes ago that there was a 3-way bidding war for $LBPH in the buyout that sparked the melt-up for $DRUG, yet $DRUG is red this morning?

Hmmm...doesn't make sense to me!


Summary: Bearish NTLA: complex therapy competing against simpler drugs makes it an efficient way to lose money.

$NTLA Making new 52Wk lows constantly.  That's what you get for taking complex therapy into spaces already adequately treated by simpler drugs.

Cool (and frankly quite successful) science experiments.  Simultaneously an incredibly efficient vehicle for losing money.


Summary: Long NKTR into AD trial readout; trades below cash value with upside not priced in, disagreeing with bearish view.

This is clearly how the market views the company as well given that it trades far below cash value (not to mention potential $ infusions via Dapi royalty monetization and Lilly lawsuit payouts).  I'd bet that if Martin spent time digging through the AD data he'd agree that there is a reasonable chance the trial hits, which is not priced into the stock at all.

Everyone is writing the company off at first glance.  IMO that's why there is an excellent opportunity here into the AD readout.

@A_May_MD Hey Adam, I saw a video of Shkreli saying Nektar are probably just going to burn money and he doesn't trust the management at all, given their track record. How would you reply to that? $nktr


Summary: Short HIMS: $16B company selling pirated drugs with no more shortage loophole protection.

Just got short $HIMS.

$LLY $NVO
Maybe we can’t prevent other countries from stealing American IP, but surely we can stamp out these IP parasites residing in our own country.

$16B company selling pirated drugs with no more shortage loophole to protect them. 👎🏻

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$HIMS Out with my 10%.  I'll be back Monday if you goons decide to run it again. 🫡


Summary: BBIO massively underpriced given Attruby script data; CYTK flagged as the next catalyst.

$BBIO 1028 scripts?!

Revise the models.

$CYTK you’re next.

$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.


Summary: Bearish HIMS: FDA declared GLP-1 shortages over, ending the compounding opportunity; expects stock to return to $20s.

Game over $HIMS.  It's done.  Goodnight.

https://t.co/fugqSydmac https://t.co/VtfpbsjIFw

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Also, absolutely HILARIOUS that $HIMS press released that they just spent money buying a peptide manufacturing facility *10 minutes* before the FDA announced that the GLP-1 shortages are completely over.   Back to the $20s where you belong, parasites.

https://t.co/MJYvdXQeTh https://t.co/Eunlt1trF9


Summary: NVO's oral peptide can't scale for mass obesity market, leaving LLY's Zepbound dominant in the mega-TAM space.

Too bad $NVO will not be able to scale this oral peptide drug up to 150x-300x the API that Ozempic/Wegovy require!  This is not a mass-obesity market drug.

A profitable drug in a niche market?  For sure!

But definitely not an answer to or competitor in the Wegovy/Zepbound "biggest TAM ever" space.  $NVO $LLY


Summary: Bearish ACRS, ANAB, QTTB: TSLP/BTLA MOAs failing in atopic derm with high placebo responses; dupi/lebri dominate and alternatives face insurmountable hurdles.

Now $ANAB BTLA fails in AD with high placebo responses after the $QTTB blow up last night.  And $ANAB even disclosed a respectably high 20s baseline EASI.

$ACRS, please tell me more about your unblinded mean EASI reductions in mild patients 🧐

Dupi/Lebri will lord over all other MOAs until LOE.  Their efficacy and safety are remarkable.  AD is looking similar to the IO hunt post PD1 (and maybe the obesity hunt post GIP/GLP) - we found GREAT targets, and getting even close to them is a massive hurdle.

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%


Now $ANAB BTLA fails in AD with high placebo responses after the $QTTB blow up last night


$QTTB placebo arm just showed a 76% mean EASI reduction with their in their TSLP study, vs 74%


Summary: Bearish VKTX: data show no superior clinical profile vs LLY — same MOA, just higher/faster dosing; Viking bulls lack the proof to support premium valuation.

$VKTX zealots abound.  I have spoken my *piece* (thanks @MSollender) on the matter.  The data are all compiled here, see for yourself.  How someone could look at these data from an honest perspective and not see how the $VKTX lower dose (2.5 and 5 mg) cohorts are the obvious relevant comparators to the $LLY 15 mg cohort is beyond me.  There is no need to obfuscate with small n phase 1 trials or speculative PK/PD modeling.  The lower dose Viking cohorts give closer cumulative doses of drug, produce similar AE profiles, and lead to much closer weight loss totals.

This is not complicated.  The only reason you would need to complicate something so obvious like this is that you have an agenda to make a claim that $VKTX has shown a superior profile.  It hasn't.  They have just given a hell of a lot more drug a hell of a lot faster.  People are bending over backwards trying to find a way to suggest that Viking has proven a superior clinical profile because they've got a story to sell you.

One last piece of perspective:  Why would my claim (that two drugs with the same MOA are *similar*) be more controversial/harder to prove than these people's claim that $VKTX's drug is *SUPERIOR* to $LLY's (again, a drug with the SAME MOA)?  The burden of proof is on the overzealous Viking bulls.  They don't have it.

@GilaMonstrum My comparisons are not based solely on safety.  They are based on everything -->  Safety, efficacy, and cumulative dose administered.  As you know, the 2.5 and 5 mg $VKTX cohorts are closest to the $LLY 15 mg cohorts on EVERY SINGLE ONE of those aspects.  This is why I keep https://t.co/9UMGJnIDls


$TMDX is toast. Their entire business model is garbage, the revenue stream is largely based on a bizarre form of racketeering, and new technologies/practices that make $TMDX totally obsolete are already being adopted.

Summary: Short TMDX: racketeering business model, regulatory/legal threats, surgeon defections, obsolescence from cheaper competing devices, and declining revenues signal a death spiral.

$TMDX is toast.

I started reading the @ScorpionFund report as soon as it came and and have gotten through almost every slide.

There are undoubtedly major government/regulatory concerns here that could kill the company cold.  Both from medicare investigations (almost certainly happening soon if not already - heads up @MartyMakary ), FDA concerns, possible organ trafficking law violations, kickback violations, and even members of congress already calling out the company's practices.

But really, you don't need to know any of those existential regulatory/legal threats to realize the company is done for.  Their entire business model is garbage, the revenue stream is largely based on a bizarre form of racketeering, and new technologies/practices that make $TMDX totally obsolete are already being adopted.

They launched as a device to make transplant surgeons' lives easier by keeping organs healthy for longer.  Their initial launch served as a foot in the door to get the business going, and they have now pivoted to a racketeering scam using insanely overpriced and overutilized air transport services to move organs, surgeons, and company employees all over the country, even when there is no need for the long flights they opt for.  Hospitals are then billed for the excessive fees with absolutely no itemization or price transparency, and then medicare covers it all (likely having no idea what they are paying for) due to archaic language in medicare contracts that is due to change.

Also, the whole purpose of the $TMDX device is to increase how long an organ can remain healthy outside of the body.  In theory, this should INCREASE the amount of distance where it would be considered safe to *drive* an organ from point A to point B instead of having to use expensive private jet travel to get it there faster.  Historically, this radius has been 250 miles - further than that, you fly the organ - within that radius, you drive it.  However, $TMDX appears to be flying *all* organs (again, often including multiple jets to fly company employees/technicians as well), even those within the 250 mile radius.  This is absolutely a scam when you consider the fact that the entire purpose of the device is to prolong out of body time, which should allow hospitals to *save* money by driving organs that are even FURTHER than the 250 mile radius...

But even beyond the evidence that the company is now just an air transport racket (which for some reason bought $13M luxury jets for its fleet instead of the ~$2M jets that are typically used in this industry 🤔), you can also see they're doomed by the glut of new and MUCH CHEAPER devices that are coming into the market soon.  The surgeon's interviewed all seemed to agree that using these new devices is a "no brainer".  That's also on top of the fact that some US hospitals are now starting to use a procedure called "Normothermic regional perfusion" which basically negates the need for a device like $TMDX to begin with in some cases.  This technique has been standard of care in Europe for over 20 years, and the US is just now catching up.

And on top of that, Scorpion has shown that transplant surgeons/centers clearly have come to *DESPISE* working with $TMDX.  Keep in mind that the company completely changed their business model after initially launching as a reusable unit with disposable parts, to now becoming a fully "disposable" unit that also comes with massive air transport services/fees that the company coerces you into using and paying.  Surgeons started using the product under the old model, and liked it.  With the bait and switch model change that the company has used, it appears many surgeons now cannot stand $TMDX and will no longer work with them.

The quotes in there from some of the top transplant surgeons/centers in the world are absolutely scathing.  Several of the large transplant centers interviewed here noted that they have just in recent months stopped using the company's services altogether.  This is extremely important because this basically proves that $TMDX's stalling/declining revenues (that the market has already been spooked about) are because surgeons are abandoning them, NOT because transplant volumes in general were down in recent months across the entire market like the CEO has tried to claim.  To me it looks pretty obvious that revenues are down because they're at the beginning of a potential death spiral, despite the CEO's repeated insistence on recent quarterly calls that nothing is wrong.  These transplant centers are saying loud and clear that $TMDX is done.  And this is the market talking - NOT the government/medicare, which also appear to have their own reasons for potentially shutting down this racket altogether following investigations into their ridiculous practices.

@ScorpionFund has a great track record with shorts like these.  They do good work and find true instances of egregious corporate practices and company valuations.  I think this $TMDX report is likely to become another big win in their track record.

Of course, if you followed @cigs1234 you could have known that $TMDX was a terrible company and investment *way* before Scorpion called it out, because @cigs1234 has been incessantly pumping this name, tweeting about it literally dozens of times since only August.

It's down >60% since his first tweets about owning it just those few short months ago, with lots of supossed dip buying along the way.  He is truly one of the worst "in the industry" (quotes there because he's clearly *not* "in the industry"), and an incredible account to follow for fantastic short alpha!

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https://t.co/0c8A9b00wG


Summary: Bullish FULC: Oxbryta withdrawal removes a competitor and eases SCD trial enrollment, a key overhang.

The most common complaint/concern I’ve heard regarding $FULC SCD program is that the current trial restrictions the FDA implemented have just made it way too hard to enroll the trial.

With $PFE $GBT Oxbryta being taken from the market, a bunch of the more severe SCD patients are suddenly having their medicine (perhaps “medicine”) being taken away from them all at once.

Terrible way to find good news for $FULC, but it is what it is.  Trial just got a lot easier to enroll.


Summary: Bearish on Roche's oral obesity drug: >80% nausea vs ~30% for existing competitors makes it unmarketable.

I mean, what do you think I'm missing?  All 3 dose levels of the $RHHBY oral drug showed >80% nausea.

Obviously some degree of nausea is acceptable.  But compare this to what's on the market already with ~30% nausea signal.  Why would this >80% nausea signal be seen as a competitive profile?  That's simply not a marketable profile against the competition.

Obviously I understand that the obesity market is gargantuan.  That doesn't mean we should close our eyes and throw money after every obesity drug that finds its way into a clinical trial, right?  Don't the actual data of individual drugs matter at all?

@A_May_MD Not arguing for one drug or another but you are missing the bigger picture here. The market (I.e. enough of the 100mm obese people in US and 1bn worldwide) will accept some nausea and vomiting to lose weight. This class of drugs will be ubiquitous, and some may fail on the way,


VK-2735 isn't more efficacious than $LLY Tirzepatide. Viking has just been giving more drug faster in their early trials and creating more tolerability adverse events. 'Tolerability normalized' cross trial comps make the drugs look essentially the same

Summary: VKTX bearish: VK-2735 shows no efficacy edge over LLY's Tirzepatide once tolerability-normalized; same MOA undermines bull case.

Hot (data-driven) take for our $VKTX fans.  VK-2735 isn't more efficacious than $LLY Tirzepatide.  Viking has just been giving more drug faster in their early trials and creating more tolerability adverse events.  "Tolerability normalized" cross trial comps make the drugs look essentially the same, which only makes sense, because...they have the exact same mechanism of action...

---

Here's a quick-reference table for the efficacy/safety numbers $NVO sema, $LLY TZP, and all 4 dose levels of $VKTX P2a for folks to use as well: https://t.co/DcvxRVAGPT


VK-2735 isn't more efficacious than $LLY Tirzepatide


they've dosed like a hundred patients in FDA-backed studies already, so they're off to the races!

Summary: Bullish VIR: novel masking technique harder to copy, substantial FDA-backed clinical progress underway.

Could be, but this is at least a more novel technique than the stuff that had classically been “copied” like ADCs and naked TCEs.  Especially if considering the double masking candidates that $VIR has.  Not to mention, they’ve dosed like a hundred patients in FDA-backed studies already, so they’re off to the races!

@A_May_MD totally agree with you here. I own $VIR and have been looking at $JANX.  I wonder if the valuation discount is due to fears that a random Chinese competitor appears out of the blue yet again.


Summary: TARS at $43 seen as oversold collateral damage from RFK-driven XBI selloff; implied buy opportunity.

@Maximus_Holla Seems like commercial stage small/mid stage bios should be *the most* immune to this RFK fear that’s causing $XBI to sell off as well.  $TARS in $43s this morning feels like the baby getting tossed with the bath water, but we’ll see!


Summary: BEAM is overvalued relative to VERV's drawdown given its 50% ownership stake; should be down more from here.

@crisprtalk Not if you consider 50% ownership of the $VERV asset that is now on hold.  This current $BEAM drawdown is not even proportional to that’s $VERV drawdown adjusted for market cap.  $BEAM should be down even more based on that alone (in a vacuum).


Summary: Strong buy on TECX: insiders paid a premium in PIPE, stock now 70% below insider price 1 week later with no negative news — historically unprecedented setup.

$TECX move is absolutely *astounding* to me.

>First of all, I had never ever seen an example of multiple insiders ponying up to pay a PREMIUM to what funds are paying in order to participate in a PIPE ($54.14 vs $50).  Massive vote of confidence.

>Second, I have *definitely* never seen the opportunity to buy a stock with a ~70% upside to what the insiders paid literally a week after they bought in, with no news ensuing since their purchases.

The fact that both of these never-before-seen factors are occurring on the *same* stock...It's seriously hard for me to even fathom.

$TECX is really one of the most bizarre sell-off case studies I have ever seen at this point.

lot of these moves are just...wow

JANX and NAMS have completely given up their Dec gains. Both of these still have plenty of clinical risk but does anyone really think they should have puked their entire gain?

TECX is trading 40% under the private placement 8 days ago


I'll take that bet to say it trades/closes below that level again this year

Summary: Disagrees with parent's bullish thesis; expects HIMS to revisit/break below the ~$52 May low again before year-end.

@himshouse $HIMS low of the week is what ~$52?  I’ll take that bet to say it trades/closes below that level again this year 🤝 🫡

$HIMS SETTING UP FOR A BIG JUNE 🔥

I think we'll look back on the week of May 4-11 as the bottom for 2025. Google Trends are rebounding hard. App rankings just had best WoW gain since April. Credit card data off lows.

Here's our full $HIMS Data Tracker recap:

(link below) https://t.co/GbwVLsIs1H


Dudum knows what the bears know. The core business acceleration is slowing badly, GLP1s won't save their growth forever...IMO he is selling because he knows that right now the getting is good, and it won't always be.

Summary: Bearish HIMS: CEO dumping ~$114M in stock signals insider knows slowing core business, GLP-1 tailwind fading, and $12B valuation unjustified.

$HIMS CEO Andrew Dudum continues absolute *DUMPING* stock on the $HIMS cult.  He just sold 666,000 shares for ***$33,562,320***

The $HIMS cult thinks the low $50s is a "dip" to buy.  Meanwhile the CEO is dumping tens of millions of dollars at...$50.58/share...

Dudum knows what the bears know.  The core business acceleration is slowing badly, GLP1s won't save their growth forever (whether there is a $NVO lawsuit or not), and upcoming vertical launches are going to be *massive* challenges compared to stuff like ED and hair loss.

Of course, he is entitled to reap some rewards from building this business...but there have been a LOT of big sales at levels that his retail cult considers a "dip".  How much cash does he need *right now* to live his lifestyle?  Surely not *this* much, right?  IMO he is selling because he knows that right now the getting is good, and it won't always be.

You guys really want to be buying $HIMS at a $12B valuation and a billion dollars of convertible debt?

Ok...Andrew is selling to you!

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$HIMS Cult:  “Nooo this $HIMS insider sale is no big deal”

*a sale so large that zerohedge tweets about it*

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And GURGAVIN on the $HIMS insider dumping too

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You can add up the $HIMS CEO sales here if you want - I asked chatGPT how many sales in the last year.  It says ~3.4M shares for ~$114M.

YES I know that CEOs sell.  But this is a *lot*, and don’t act like you all wouldn’t be bullish as hell if he was out here buying instead! https://t.co/NMwBspWC4k

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Multiple $HIMS bulls are trying to tell me the $HIMS CEO’s massive sale was pre planned via a 10b5-1 plan...  Y’all are just making shit up without even checking?  Look at the filing.  This was an open market, NOT pre planned sale, per the filing with the SEC. https://t.co/WSpicFjyJR

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Interesting press release “explaining” the $HIMS CEO stock sale.  NGL I actually thought the companion music video was pretty good:

 https://t.co/KSQUfu4GaX


Summary: Expects significant further upside in LXEO once the market recovers, citing positive data.

$LXEO recovering to just flat from their inarguably positive data…*when* we do recover for real, $LXEO has significant further upside in it in my opinion.  Time will tell!


Summary: LLY up on orforglipron tolerability data; VKTX hurt as rival's profile undercuts Viking's competitive position.

$LLY orfo with lower rate of nausea than TZP 15mg…

Did anyone have that on their bingo card?  $LLY up today.

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Sorry to my dear $VKTX family members but this tolerability profile from $LLY is not what Viking wanted to see.


Summary: Long REGN on smarter strategic acceleration; SRRK still cheap on SMA silver-mine despite a strategic misstep.

Interesting and I think wrong decision.  New management clearly never would have even run this study had they been around before, because the data are as good as they could’ve hoped for at the outset.

They’re decelerating this, $REGN is accelerating this.  I think REGN is making the smarter move.

Fortunately for SRRK there sitting on a silver mine for SMA that will be a gold mine if Roche misses.  Still cheap for SMA despite what I think is a strategic error here.


Still cheap for SMA despite what I think is a strategic error here