You can still short $NTLA at a >$1.5B valuation? >2x higher than it was a few months ago? Don't mind if I do!

Summary: Actively shorting NTLA citing Hy's Law safety signal; sees valuation as still inflated despite recent decline.

I told you $NTLA was toast.  Vindicated.

Shut it down.

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You can still short $NTLA at a >$1.5B valuation?

>2x higher than it was a few months ago?

Don’t mind if I do!

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Hy’s law.

Night night $NTLA

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“They’ve crossed the threshold which would meet the traditional definition of Hy’s Law”

$14.50 right now lmaoooo ok guys.

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$NTLA #Hy’sLaw https://t.co/Uy99bkr9bS

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$NTLA


Summary: Bullish NKTR; author argues the AA signal is more convincing than the prior AD signal that the market doubted but proved correct.

structural marker; pre-classified as canonical yfinance ticker

@hannibalspeaks And the naysayers (and market at large) said the AtD signal was fake.   Obviously I disagreed then, as I do now with AA.

IMO the AA signal is even more convincing than that P1b AtD signal ever was 🤷🏻♂

@A_May_MD Your great win in the AD readout came from microanalysing a much smaller sample. No harm in looking at $NKTR has in AA, and comparing to the dozen or so studies of similar size. There are red flags IMO.


Summary: Bearish NTLA: platform has safety/efficacy issues vs existing HAE treatments; stock should trade below cash.

3 $NTLA HAE patients have continued having attacks out to 1+ year.

5 $NTLA HAE patients have continued having attacks out to ~6+ months.

$NTLA’s most recent update headline prior to this (which didn’t move the stock) was “100% of patients attack free”.

Good luck pumping this, $NTLA cult 😂

You’ve got a platform that just killed someone in a disease where simple pills/shots already offer a borderline cure, and there’s a whole lots of breakthrough attack lines on that graphic below.

$NTLA should trade below cash.

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“bUt ThE sTuDy WaS dOuBlE bLiNd”

Yeah, so are literally *all* of the HAE studies that we compare this too...this is not an “excuse” for all the breakthrough attacks.

Like I’ve said so many times:  The efficacy is impressive for a totally new modality.  However, we already have multiple shots and pills that are HIGHLY effective without the risks (now both known and unknown) of permanent gene editing.

It’s “cool” that they’ve been able to accomplish what they have, but it’s just not a viable approach for this condition in the modern day.  Especially given that the efficacy isn’t perfect and now with the potential need to worry about fatal side effects.


Summary: Agrees maintenance will hit, implying ABVX price above $116 and toward $150+.

@DueDoctor @semodough Yes and the cool part is that maintenance is gonna hit 😎

@semodough $116 is too low for $ABVX

If maintenance hits $150 minimum


Summary: Implies VKTX could/should be acquired at $60, a bullish buyout price target.

@emircan_sahinnn Idk 🤷🏻♂ they should take $60 if they can get it

@A_May_MD At what price would you see VKTX getting bought in this scenario ?


Summary: Bullish QURE: argues mHTT CSF measurement is irrelevant to approval; prespecified primary endpoint p=0.003 supports approval.

mHTT measurement debate is basically pointless for $QURE

Femtogram/mL concentration in the csf…concentrations so low that you can’t even capture it with ELISA, and the rest of the brain (that wasn’t injected) is still making mHTT.  Cant really measure it very accurately, and then given that only the striatum has been treated, mHTT in the CSF probably wouldn’t change with $QURE’s approach even if you could. The rest of the brain keeps making it.

I’m not saying this means the drug works.  But they’ve got all the ammunition they could ever ask for to ignore CSF mHTT altogether.

So, back to the prespecified PE p=0.003

Approved.

@EmuConspiracy @A_May_MD @anthonystaj The drug doesn't seem to affect mHTT and if it does, will worsen dz progression just like tomi. Need to spare wtHTT.

Retarded approach, after tomi failed all these programs should've been axed.

Hope this helps.


Summary: Bullish NKTR: reddit patient anecdote driving the dip is old, unreliable, and inconsistent; 1,000+ patient safety data for Rezpeg remains intact.

Regarding the $NKTR "dip" on the patient anecdote:

Really the only thing that surprises me here is that there was somehow still a serious investor somewhere who didn't already know about these posts.  These posts have been going around biotech investing circles already for months.  I have had multiple people messaging me about this reddit poster since over two months ago.

Obviously it should go without saying that anonymous reddit posts are not reliable sources of medical data, but beyond that, there a many inconsistencies in this "story" that speak out against any sort of dangerous liver adverse event.

The original post spoke about "liver pain" and "pale stools", which are not typical components of a drug reaction.  There was also clearly no sequelae of whatever (potential) lab abnormality may have been observed, and there was not any intervention needed.

Furthermore, if you dig through this reddit account's history, you'll see some highly questionable stuff.  I'll leave most of that out, but there's at least one very important example -> This person has literally posted admission of illegally purchasing and abusing prescription narcotics.  *If* there was actually a liver enzyme elevation observed in this patient, it is valid to consider what exactly may have caused that given what we know.

Another strange element...The original post was made well over 2 months ago, and then inexplicably deleted.  It stayed deleted for multiple weeks, until, 2 days ago, the whole thing was reformulated and posted again by the same user.  Odd.  *Especially* in the context of this user having posted that they were trading $NKTR stock *while being enrolled in the study*...Not sure what to make of all that...

I think we should also note that there are now >1,000 patients dosed with Rezpeg (largely due to the large P2 trials in Lupus and AtD) which showed no sign of an LFT elevation problem.  Almost all studies of 1000+ patients will show random (<1%) low grade LFT elevations without clinical sequelae.  This phenomenon is likely due to a variety of potential explanations such as viral infections, alcohol consumption, or illicit drug use, which are all captured at low baseline rates in large studies.  We have robust data supporting the safety of Rezpeg, and this reddit anecdote of dubious quality (and potentially of dubious intent) does not, in my opinion, undermine the 1,000+ patients of safety data we have.

Besides all that, again...this literally isn't even new news.  These anecdotes are *literally* months old, just having been previously deleted and now recently re-posted.  If you're a pod that shorted $NKTR on this nonsense today, keep that in mind 🫡

$nktr Just to elaborate on what @Biohazard3737 is saying. Fake news 101! Pt 69 days ago makes a post before AtD data about their AA trial. Initially super happy with Rezpeg then suddenly has some liver trouble.
Picture 1 - proof of above 69 days ago
Picture 2 - seemingly https://t.co/bByzc9Md24


$NKTR will have the preferred 2L AtD drug if they can simply repeat their P2 AtD data in P3… $NKTR will have a *huge* differentiation factor that applies to a quarter of the gargantuan atopic derm market

Summary: Bullish NKTR: updated escape-arm AtD data holds up, asthma signal adds major differentiation for ~25% of the eczema market; expects P3 repeat to confirm preferred 2L positioning.

$NKTR provided updated data on the escape arm AtD patients this weekend, as well as some interesting asthma data.  Worth keeping track of both!

The updated AtD crossover data held up well with increasing sample size.  The comp still looks quite tight with Lebri in its crossover study (updated data in attached table).

Note that the biggest qualm with the $NKTR dataset here is the attrition in sample size, which likely selects for responders continuing on treatment (visible in sample sizes on 2nd photo).  This is something to watch, but do note that the lebri comp we are using here was *also* an "as observed" analysis that leads to enriching of response rate.

We can also look at an "as observed" analysis of OX40 with Rocatinlimab's "Rocket Horizon" study (3rd picture).  This showed 47% EASI75 and 26% EASI90 at week 24 (vs 60% and 37% for $NKTR's crossover patients).  Note here, though, the rocat data are "as observed", but not open label like Nektar's crossover patients.

Now, as for the asthma data.  Dupi is the only eczema drug to have ever shown efficacy in respiratory conditions.  It is a bit perplexing as to why, but OX40, and even lebri with its overlapping MoA have failed to impress on asthma.

Is it stands, Dupi is the only drug you've got when your eczema patient also has asthma.  What's crazy is that this is 25% of the atopic derm market that also has eczema.  That's a HUGE chunk of patients.

So, even though I think it is already clear that $NKTR will have the preferred 2L AtD drug if they can simply repeat their P2 AtD data in P3, there would be almost no argument *against* that for the quarter of eczema patients who have comorbid asthma.

Why start your eczema+asthma patient on any other drug when you've got a medicine that treats both?

$NKTR's asthma data come from their atopic derm study, which almost perfectly reflected real world comorbid asthma rates with ~100 asthma patients enrolled among their ~400 atopic derm study.

The early data are impressive, with placebo adjusted effect magnitudes looking comparable to dupixent on asthma QoL metrics (4th photo & credit to @CloisterRes because I'm too lazy to overlay the images rn).  Note that there were statistically significant effects already observed in a small P2 study...

Caveats abound for this.  It wasn't an asthma study, and the absolute effect size is a bit small given placebo worsening.  That said, placebo response kinetics are quite different when the disease activity you're measuring isn't actually the disease that you're enrolled in a study for.  The deltas are still what I am paying attention to here, and they look quite good for $NKTR.

For me, the asthma takeaway is that they were somehow able to already make statistically significant improvements in asthma symptoms in a P2 study that barely set out to measure that disease in the first place.  Why wouldn't these results repeat in P3?  If that's the case, $NKTR will have a *huge* differentiation factor that applies to a quarter of the gargantuan atopic derm market.

That would be a big deal, and this entire asthma angle was never even on my bingo card for $NKTR to begin with.

$NKTR data update just now exceeded even my bullish expectations/hopes.

Here's a breakdown of the situation and relevant data  (the end is the best part)
👇👇👇

Most of the presentation today is just the P2b data that we already had.
❓So what's new❓

$NKTR ran an "escape arm" https://t.co/UF8pWrHOGE


Up. Study isn't powered for binary endpoints

Summary: NKTR goes up even if it misses SALT20, as the study isn't powered for binary endpoints.

@failed_drugs @meremrtl Up.  Study isn’t powered for binary endpoints

@meremrtl @A_May_MD Where do we think NKTR goes if it hits primary but misses on SALT20?


If it takes 52 weeks instead of 36 to reach max improvement (with continual improvement all along the way) that's not a big deal *at all*, especially versus indefinite treatment with a multiple fatal adverse event black box label drug as the alternative.

Summary: Bullish NKTR/Rezpeg: slower time-to-peak vs 36-week endpoint is not a concern given superior safety profile vs JAK inhibitors.

Patients in the study already had disease for ~3 years.  If it takes 52 weeks instead of 36 to reach max improvement (with continual improvement all along the way) that’s not a big deal *at all*, especially versus indefinite treatment with a multiple fatal adverse event black box label drug as the alternative.

If study time point was week 52, reckon SALT20 data would be extremely impressive. Hair growth accelerating with time.
$NKTR
Any adult with AA and cardiac history (very common in this group) would be a candidate for Rezpeg (vs JAK).


Summary: NKTR is >2x undervalued if the 2L AtD market opportunity is properly priced in.

@john_hersc79276 Yeah I don't understand what the market is missing here unless it's me missing something huge. IMO  $NKTR would be >double its current market cap if people took the 2L AtD market as seriously as it deserves to be taken.

@A_May_MD holy **** did not have a chance to read this before. The math is incredible even with very conservative assumptions.


Summary: Short-the-launch thesis is dead; near-launch biotechs BBIO/VRNA/TARS/INSM are destroying bears, and ABVX/QURE are M&A targets before they launch similarly.

10 months later, this has become the biotech mantra.  "Short the launch" was a strong and successful approach for years...Now companies like $BBIO, $VRNA, $TARS, and $INSM are just destroying that narrative.  #LaunchTheShorts

$XBI $BBC

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If I might predict the next trend, I'd say it's more/earlier M&A of this type of name, which will prevent these small biotechs from launching (like rockets) on their own.

Pharma should be jumping on companies like $ABVX and $QURE with (IMO clear) prospects so that they can bring them in house before they get a chance to pull a $VRNA/$BBIO/$INSM move, driving the acquisition price sky high.

At least for now the "Short the launch" bargain price window seems dead, and I'd be surprised if pharma gets rewarded for waiting on this batch of near-launch companies.

Get 'em while you can, pharma!


Pharma should be jumping on companies like $ABVX and $QURE with (IMO clear) prospects


I have been buying the $QURE dip... $QURE, IMO is the next in that series

Summary: Long QURE on thesis that proactive PR triggers public/political backlash reversing FDA flip-flop, analogous to SRPT/REPL bounces; also implicitly bullish REPL as a comparable that already rebounded.

I have been buying the $QURE dip.  This morning's press release was a calculated decision by $QURE management.  Note that there's a key word in the press release that I have not seen people discussing..."BELIEVES".  $QURE has not yet received formal word that they cannot submit for approval, but $QURE "BELIEVES" that the FDA is no longer going to accept the plan they had previously agreed to.

$QURE is under no obligation to release their guesses as to regulatory decisions.  So why would they make a press release like this that tanks their stock?  Why not wait for the official word to actually come in?

Because they want to start the public backlash *now*.  $QURE is getting this outrageous news out into the world proactively so that the administration gets an earful from the public about their rogue FDA's reneging on prior guidance for a fatal disease *years* after the guidance was given.

This is, in my opinion, the biggest and highest profile FDA flip flop in the history of the agency, and it is being done with a disease that has *massive* public awareness.

Like I said before, if you thought $REPL and $SRPT backlash against this FDA was big, this $QURE situation is going to blow them away.

Note that $SRPT bounced >100% and $REPL bounced >300% from their respective negative regulatory headlines, each in a matter of only a couple months.

The community around and public awareness of Huntington's disease dwarfs both of those prior two case studies.

At this rate, the headline here will have gone from "Trump's FDA clears the first treatment for one of the worst genetic diseases in the world" to "Trump's FDA reneges on Huntington's treatment, stabbing patients and their families in the back".

I personally don't think this will hold up, and it is very clear to me that the entire purpose of $QURE's press release today was to get the backlash started *before* any official regulatory decisions are made.

Frankly, it's a brilliant move by the company.  The heat is now fully on, and IMO this one is going all the way to the top (yes, I think Trump himself is going to be hearing about this).

Of course, you never know with regulatory stuff - *especially* in this confusing time, so risk remains.  But, we've already seen two regulatory crashes rebound in the last few months alone.  $QURE, IMO is the next in that series.

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As previously stated, I believe the $QURE press release last week was calculated to make it so that there is technically nothing for the FDA to have to officially “walk back”.

“What are you talking about, we never said we were changing the regulatory bar!”  — is still totally in play for the FDA.

Smart.  We will see how it plays out.  If meeting minutes don’t reflect a different story, Vinay’s shaky tenure likely becomes the next branch point.

Credit to @DesertDweller93 and @MauriceOnTW for being on top of this language in the 10Q as well.

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Well, that’s interesting.  Could be coincidence 🤷🏻♂

$QURE

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Posting mostly for the first part, but also, wtf?  Does Makary just straight up not respond to any emails?  😂 https://t.co/KVgKS4JZ0p

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Perhaps FDA staffers should submit important questions to his podcast for timely response


$SRPT bounced >100% and $REPL bounced >300% from their respective negative regulatory headlines, each in a matter of only a couple months


Summary: Bearish HIMS: bull cases built on imaginary peptide verticals are unfounded and will eventually unravel.

Drug Manufacturers - Specialty & Generic

The “peptide” snake oil & online anabolic steroid campaign has been highly profitable for a select group of people willing to push legal boundaries and ignore medical & ethical standards for proving drug safety/efficacy.  In some ways it’s a testament to $HIMS that they haven’t entered this slimy space.  But still, $HIMS longs who clearly don’t understand the very most basic facets of what a peptide is or does, seem adamant that “peptides” beyond GLP1 are a key piece of the company’s trajectory…

Imaginary verticals may yield gains for $HIMS in the greatest bull market of all time, but eventually this bullshit will hit the fan.

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Obviously I’ve been very critical of some of the $HIMS bull cases, but I have to say that spinning the FDA approval of (another) rare disease peptide (Elamipratide) as having anything at all to do with $HIMS (or the peptide craze in general, really) is probably the dumbest one I’ve seen so far.

I’m sorry guys, but this is absolutely asinine.  Like, it’s hard for me to even remotely politely express how stupid this is - again, sorry 🤷🏻♂


Summary: Bearish NTLA after FDA clinical hold; author sees fair value below $5/share, expects stock to trade below cash.

Well that didn’t take long.  FDA places $NTLA on clinical hold.

Game over (again) @GeneInvesting

Time for this to trade below cash.  IMO, fair value is <$5/share.

@Sanctuary_Bio @GeneInvesting @Alex___VA @CoinbasedBTC @drrichjlaw @Andre_AGTC Oh man.  FDA clinical hold for $NTLA would be BRUTAL.


$NKTR's escape data look better than Lebrikizumab's!!! ... $NKTR might do we what have all considered basically unthinkable ➡ Compete with the IL4/13 class instead of just picking through its (abundant) scraps.

Summary: Bullish NKTR: 24-week escape arm data exceeded expectations, outperforming Lebrikizumab on EASI75/vIGA0/1, raising possibility of competing with the IL4/13 class.

$NKTR data update just now exceeded even my bullish expectations/hopes.

Here's a breakdown of the situation and relevant data  (the end is the best part)
👇👇👇

Most of the presentation today is just the P2b data that we already had.
❓So what's new❓

$NKTR ran an "escape arm" in this study for placebo patients who failed to improve during the 16 week induction period (during which time they received only placebo, no treatment).

These "escape" patients switched over the Rezpeg treatment after 16 weeks (again, assuming they had NOT responded, defined as EASI<50 response).

42 patients enrolled in the escape arm, and today we got data on the first 21 of those patients who have completed 24 weeks of treatment.

❓Why is this important❓

Because so far, we only had data showing Rezpeg responses out to 16 weeks.  When these data were first presented, the KOLs noted that it did not seem like that response curve had flattened yet, meaning longer treatment *might* mean deeper responses.  They contrasted this to the IL$/13 class (Dupi and Lebri) which they said typically have already reached their max efficacy by ~16 weeks.

Well, $NKTR's data today showed that with 8 more weeks of treatment, their responses *did* continue to deepen, and by *a lot*.

The Data 🤓
➡Original 16 week data:
      ↪EASI75     ~44%
      ↪vIGA0/1    ~23%
➡New 24 week "escape arm" data:
      ↪EASI75     ~62%
      ↪vIGA0/1    ~38%

So, as you can see, these $NKTR patients at 24 weeks had much deeper responses than the original 16 week-evaluated patients did

As always, a key question is ❓How do we compare these data to other competitors❓

Well, in the table below you will see that, even in the original 16 week study, NKTR at 16 weeks was already showing better EASI75 and vIGA0/1 response rates than the OX40 competition showed ***at 24 weeks*** in their P3s.

But what about the higher bar of competition - IL4/13?  Of course, most understand that $NKTR doesn't *need* to compete for 1L patients with IL4/13 drugs, since the AtD market is so massive.

But, here is the big surprise...There actually was a Lebrikizumab study that ran an escape arm like $NKTR did...and, at 24 weeks of escape treatment, which drug showed better responses?  $NKTR's up and coming AtD drug, or the mega-blockbuster IL4/13 class?

Even *I* am surprised to say...$NKTR's escape data look better than Lebrikizumab's!!!

The Data 🤓
➡Lebri 24 week "escape arm" data:
      ↪EASI75     ~57%
      ↪vIGA0/1    ~23%
➡$NKTR 24 week "escape arm" data:
      ↪EASI75     62%
      ↪vIGA0/1    ~38%

Although there are slight differences in the designs and this is cross-trial comp, this is actually a *very* apples-apples comparison, and I don't think anyone would have predicted that the comparison would look *this* favorable for $NKTR

Lebri is largely considered as good as, if not slightly better than Dupixent on efficacy...If this signal for $NKTR showing continued deepening of responses versus a flattening of responses for Dupi/Lebri is actually real/reproducible...

...Then $NKTR might do we what have all considered basically unthinkable ➡ Compete with the IL4/13 class instead of just picking through its (abundant) scraps.

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Already fielding some "but  $NKTR data was open label" comments.

Guys, so is this Lebri data!!!  And $NKTR *smoked* it at the 24 week timepoint, especially on vIGA0/1.


It's hard to overstate how massive it is to be not just the *first* but also the *only* drug with a unique MoA and a large/impressive dataset in big TAMs.

Summary: Bullish on ABVX and NKTR as rare first-and-only drugs with unique MoA and large datasets in big TAMs, making them highly attractive M&A targets.

I keep making this point about $ABVX and $NKTR

It’s hard to overstate how massive it is to be not just the *first* but also the *only* drug with a unique MoA and a large/impressive dataset in big TAMs.

Just a huge, huge deal, and *exceptionally* rare in today’s biotech.

Great M&A slides from Lifesci Capital.
Interesting to see  acquirers are mostly interested in "unique" programs in term of biology (new mechanisms, platforms and modalities) or stage (first in class)  with limited appetite for more incremental improvements or less differentiated https://t.co/7uia3fMNWN


I keep making this point about $ABVX and $NKTR


Summary: Bullish both SNY (half-decade lead in OX40 class) and NKTR (market share gain on P2 repeat) in 3rd-line atopic dermatitis.

@crypto1nfern0 It’s a real market but SNY will take it with this lead time (half a decade or more), and now $NKTR is going to take more market share if they can simply repeat P2 results.

@A_May_MD Curious why you are so bearish on the class.  News is clearly bad for $SNY and great for $NKTR. But is the OX40 class not good enough for 3rd line after Rezpeg?  Will that not be a real market?  Is the decining efficacy from wk16 to wk24 a deal breaker?


$NKTR is going to take more market share if they can simply repeat P2 results


Summary: Long PALI; new VP hire adds legitimacy, valuation remains cheap relative to IBD peers ARNA and ABVX, expects more credit ahead.

$PALI further proving its legitimacy by bringing Sharon Skare on board as VP of clinical operations.  She previously served in the same role, in the same disease (IBD) at…

➡ $ARNA - bought out for $6.7B after phase 2 data
➡ $ABVX - currently ~$7B, likely to be bought out (***in my biased opinion***) north of $10B after phase 3 data

$PALI’s valuation remains cheap, IMO, continuing to reflect skepticism about the PDE4 MoA in UC.

Years ago, I watched these ex-$ARNA employees joining another tiny IBD company whose drug the market was *very* skeptical of….that was $ABVX.

Still early days for $PALI, but hopefully it gets a little more credit along the way than $ABVX did.  The gap from $8-$98 moved quickly…a more reasonable market won’t ignore $PALI for years.  Maybe $PALI could even get the $MORF treatment (i.e. *LOTS* of credit very early) 😅

THIS IS 🚨NOT🚨 A PITCH, but the $PALI story is a fascinating one, and I am currently long (and bought more this morning).

This is a wild story of a nanocap biotech that was valued at ~$8M only a few days ago, but has now burst onto the scene with a potentially unique approach


I personally do think the study is showing a real effect, and there's plenty more biologic plausibility with this drug than with failed predecessors

Summary: Bullish QURE; author believes trial shows real effect with stronger biologic plausibility than failed predecessors.

The edgy/cool kid stance to take seems to act supremely confident that $QURE doesn’t work.

Skepticism is necessary for biotech investors, so I get it.  I understand the concerns.

But, I personally do think the study is showing a real effect, and there’s plenty more biologic plausibility with this drug than with failed predecessors.

All I can say for certain is to speak for myself that if I were diagnosed with Huntington’s I’d be seeking this treatment.

@A_May_MD As one of the best at analyzing data Adam, does $QURE's treatment work?


$NTLA is dead but there's plenty of decay left to set in

Summary: Bearish NTLA; expects further price decay from current levels.

@zapunyo @GeneInvesting Yes $NTLA is dead but there’s plenty of decay left to set in.

Is what it is 🤷🏻♂


I have shorted $JANX after hours. ORR and mPFS are just not good. Probably belongs right around cash (~$17/share) where $VIR already trades. Maybe even below cash unfortunately.

Summary: Short JANX after hours; disappointing ORR/mPFS data, stock likely worth only ~$17 cash value or below as flagship PSMA program appears to be failing.

Pains me to say it, but...I have shorted $JANX after hours.  Sure PSA responses got worse - they almost had to with how good they looked in the n=16.  But ORR and mPFS are just not good.  I strongly suspect that in a big pharma's hands they wouldn't even take this program forward.

Not enough responses, and not durable enough when they happen (what's the cORR by the way?).

Probably belongs right around cash (~$17/share) where $VIR already trades.  Maybe even below cash unfortunately.  PSMA was supposed to be their ticket...EGFR has always been talked down.  IMO it looks like the flagship is going down.

Bummer!

---

Oof.  CEO response to cORR vs uORR question on the call was brutal, down to his tone in answering (sounded very annoyed to have been asked).

The response was basically a grump "IDK".  Bad.


Summary: Expects ABVX to eventually be acquired at a premium to current price.

@thetwitabides I honestly have no idea.  I just think $ABVX is going to someday be bought out for more than it costs to buy the stock today 🤷♂

@A_May_MD AM,

Do you think the Soffinova sales are any kind of a meaningful tell as to whether there are current discussions or an imminent deal?  TIA


Summary: Endorses CDTX buyout rumor; bullish on biotech broadly via XBI.

$CDTX buyout rumor per FT.  Believe it.

Biotech is absolutely on fire! $XBI $BBC

In all the commotion of the last couple days, I didn't get a chance to comment on the super interesting new data from $CDTX.  Very cool and novel drug that probably hasn't yet gotten the hype it deserves.  Might this be the drug that replaces the flu vaccine?!

This could be an https://t.co/GrLHjIRshP


Summary: Long ABVX as a top M&A target; expects bullish M&A premium projections may even be exceeded in current frothy pharma-bidding environment.

$155 for $CDTX was the “stab in the dark” guess of a man who was deeply scarred by the last 3 years of vicious biotech bear market 😅

That said, the actual bid of $221.50 is an INCREDIBLE premium for $CDTX.

Biotech M&A is on the hottest streak I’ve ever seen not only in terms of volume of deals but also the premiums they are fetching.

Consensus M&A names are going like hotcakes and literal post-tender offer bidding wars are erupting ( $MTSR and now $AVDL today)!  Those have always seemed like a myth/legend to me, and we have been in 2 of them this month alone…

…I’ve never seen this in biotech.

I might need to get my hands on more M&A names at this rate…obviously you all know my favorite is $ABVX, but I still want them to wait for post-maintenance data before selling…at this rate even my bullish M&A premium projections could be trumped in this frothy pharma-bidding market!

Thoughts on other “M&A names”?

---

Take it slow, Marc.

---

There’s almost no way $CDTX got to $221.5 without a bidding war having gone down.

Love to see pharma duking it out and driving premiums higher, whether it’s before or after the first offer is announced.

---

$QURE would’ve been flirting with triple digits on this rally btw https://t.co/BEPc3NSYmr


$HIMS core is dying faster than even I, a bear, expected. This is increasingly getting closer to 'just a GLP-1 company' no matter how many times the bulls say it's not. BTW, once GLP-1s go generic, they'll be just part of the 'core' as well, as everyone else will be making them and selling them cheaply too.

Summary: Bearish HIMS: core metrics collapsing, GLP-1 dependency rising, generic competition and compounding regulatory risk threaten the business model.

$HIMS core is dying faster than even I, a bear, expected.

This is increasingly getting closer to “just a GLP-1 company” no matter how many times the bulls say it’s not.

BTW, once GLP-1s go generic, they’ll be just part of the “core” as well, as everyone else will be making them and selling them cheaply too.  And that’s *IF* the $HIMS “personalized” compounding scam doesn’t get shut down before then.

📉📉📉📉📉

$HIMS I say again the data are horrifying

November
Orders: -18% y/y
New orders: -30% y/y
Downloads: -27% y/y
MAU: -13% y/y


My thesis has not, but I do understand why the market will sell QURE today on "readthrough"

Summary: Maintains bullish thesis on QURE despite expected sell-off on BHVN readthrough; views the selldown as unwarranted given different FDA divisions.

@Cattletech My thesis has not, but I do understand why the market will sell QURE today on “readthrough”.

I personally didn’t like BHVN odds as previously stated.

Let’s also remember than these drugs are under two different divisions at the fda — CDER (BHVN) versus CBER (QURE)

@A_May_MD Has your thesis changed post $BHVN?


Summary: NTLA going lower from current mid-$10s.

Guess I won’t be able to join Tony’s $NTLA spaces now!  After all we have been through, why block me now?  It almost seems like there’s something he wants to stop me from speaking out about at his event 🤔 🤷🏻♂.  Weird!

Anyway, $NTLA mid $10s right now.  Going lower, btw. https://t.co/jWmcaA7ScY


the borderline feasible dose levels of $VKTX oral are clearly inferior to Tzp SubQ on WL at 13 weeks… All that for a regimen that appears likely to be inferior to SubQ TZP based on available data. Tolerability clearly doing $VKTX no favors here either.

Summary: Bearish VKTX: oral drug inferior to Lilly's tirzepatide on weight loss and tolerability, with massive API headwind; dismisses superiority claims as false.

This is just quick and dirty comps and I'll do cleaner work on this later, but the borderline feasible dose levels of $VKTX oral are clearly inferior to Tzp SubQ on WL at 13 weeks - both absolute and placebo adjusted.  And keep in mind, even 30/60mg QD is still 14x and 28x more API for $VKTX than $LLY TZP uses.  That's still a TON of API, and a huge headwind for the company.

All that for a regimen that appears likely to be inferior to SubQ TZP based on available data.  Tolerability clearly doing $VKTX no favors here either.

I tried highlighting the absolute BS the $VKTX pumpers like @Pharmdca were constantly making up to pump the stock - the nonsense about perfect tolerability and superiority to Lilly's TZP were demonstrably untrue.  I got tons of pushback on this from people with plenty of insults mixed in.

That's often what you get for using data to try to help on here!  People prefer to listen to the pumpers saying BS that you want to hear than people using the data to make informed/balanced takes.

Let's get more balanced/data driven takes on here, stop attacking people just because they say stuff that isn't bullish your stock, ignore the vacuous pumpers, and we will all benefit from it!

In the meantime, let's put all this "$VKTX has the superior drug!" bullshit to rest now, please.


When drugs start working in neuro conditions that drugs don't work in $QURE $PRAX

Summary: Bullish on QURE and PRAX as drugs begin succeeding in historically treatment-resistant neurological conditions.

When drugs start working in neuro conditions that drugs don’t work in
$QURE $PRAX https://t.co/d1naR9fgZq


Summary: Bullish NKTR: 17% delta meets sellside bar, drug confirmed active in AA; ex-ineligible patients result would've been >24% delta, thesis intact.

$NKTR 17% delta in ITT population is solid, definitely active, and meets the sellside bar of >15%.   However, on the call we will hopefully see what the reasons were for the erroneously enrolled ineligible patients that supposedly brought this result lower than it should’ve been.

With those 4 ineligible patients excluded from the trial this would’ve been a fantastic result with >24% delta and the stock would be up a ton.  Hopefully we get some granularity on what the protocol violations on enrolling those patients were.

Mixed result given that situation.  At the very least the drug is definitely active in AA, and the post JAK maintenance hypothesis is certainly well in play.


the readout is majorly upside skewed. Rezpeg as a multi-indication derm drug could be *huge* and that is not at all priced in imo. As I've said, ~$1B just for the AtD opportunity alone even if AA fails is very cheap from my perspective…the valuation mismatch is extreme here

Summary: Long NKTR: readout upside skewed, rezpeg multi-indication potential hugely undervalued, ~$1B AtD opportunity alone not priced in.

Yeah I’ve been on record at ~50% PoS for this $NKTR readout*.  Despite the not necessarily overly bullish PoS, I still think the readout is majorly upside skewed.  Rezpeg as a multi-indication derm drug could be *huge* and that is not at all priced in imo.  As I’ve said, ~$1B just for the AtD opportunity alone even if AA fails is very cheap from my perspective…in AtD this looks like what $SNY thought OX40 could’ve been, and $SNY lost ~$10B on the day of that disappointment…the valuation mismatch is extreme here.

*I might adjust my PoS upward a bit given this preannouncement 😅

@lame_karma @A_May_MD Adam was thinking 50/50 if I'm not wrong, and this "leading dermatologist" is thinking 70/30, so even more bullish than Adam lol


$ABVX scarcity value just went up even higher. $ABVX has everything $LLY hoped that $MORF would have *and more*. $LLY should, IMO, absolutely be added to the list of pharmas interested in acquiring $ABVX

Summary: Bullish ABVX: MORF drug discontinuation raises ABVX's scarcity value as M&A target, with superior efficacy/MoA vs failed MORF asset LLY paid $3.1B for.

I had a reminder set to check $LLY quarterly deck in Q3 to see if they would advance or DC their $MORF program in UC, because this would have read-through to $ABVX.  New data today show that $MORF’s drug is going to be discontinued. Flop.

$ABVX scarcity value just went up even higher.  $LLY Lilly paid $3.1B for this asset despite the fact is had very small sample size, *OPEN LABEL* data that didn’t even look very good to begin with.  $ABVX has everything $LLY hoped that $MORF would have *and more*.

$LLY wanted a once daily oral treatment for UC with Entyvio-like efficacy and safety.  $ABVX has *better* efficacy, equal safety, *and* unlike $MORF’s drug, $ABVX has a totally unique MoA.

$LLY should, IMO, absolutely be added to the list of pharmas interested in acquiring $ABVX.

h/t @Biohazard3737 for bringing the data to my attention.


There couldn't possibly be more writing on the wall here

Summary: Bullish ABVX on M&A thesis: controlling shareholder's prior picks acquired, CEO sold both prior companies, all successful UC programs bought out recently.

@sleepydragon01 @seedy19tron And the current CEO sold both of his prior two companies.

And all successful UC programs have been bought out in recent years

There couldn’t possibly be more writing on the wall here 😅

$ABVX’s founding backer  and current controlling shareholder is sofinnova partner. The partner/MD who invested in ABVX ‘s current holding have 4 stocks other than ABVX. 3 of the 4 were already acquired https://t.co/WVdT4qx2bI @A_May_MD @seedy19tron


Summary: Bearish NTLA: autopsy findings confirm liver failure caused the death; the company is not out of the woods on liver toxicity concerns.

Context:  $NTLA just 8K'd (not a PR, hmmm wonder why) that their Hy's Law patient's autopsy showed ruptured GI ulcer and sepsis as the ultimate cause of death.

Anyone saying this is not related to the liver failure is showing their pure ignorance of medicine.

Liver failure patients don't die from their liver exploding...there is almost always a cause like sepsis (brain herniation being another "most common cause") that ultimately kills the patient.

The whole situation still would never happen without the liver disease.

This is *exactly* how you'd expect this case to have been adjudicated...this is how liver failure works.  Liver failure patients die of sepsis & bleeds ***all the time***.

Anyone telling you this means $NTLA is out of the woods on liver tox has absolutely no idea what they're talking about.

Again, might there be a reason that $NTLA covertly dropped this news in an 8K instead of press releasing it? 🤔

---

Hard to fathom anybody still listens to this dude *at all*.

Seriously, if you’re following his stuff, what the hell is wrong with you? https://t.co/DB3ChNrPAQ

---

$NTLA dopes thinking that this patient could’ve been in the hospital for 13 days with a GI perf without anyone noticing (let alone even SURVIVING that long with a GI perf - not going to happen) shows you what they know about medicine.

Absolute bullshit cope with zero foundation in medical reality.  80 year old men don’t make it 48 hours with an untreated GI perf, let alone 13 days.

He presented with liver failure and then developed the perf secondarily.  A first year medical student could tell you this.

---

There you go, morons.  From the $NTLA CEO himself.

Sincerely sorry for the derogatory language, but I’ve got nothing else for the people dumb & delusional enough to argue that this patient presented with a GI perf.  If you’re one of them, seek help. https://t.co/t35nHEb8aS


Summary: Short NTLA: FDA clinical hold + Hy's Law liver event = extinction-level threat; stock grossly overvalued at $12.50, should be in single digits.

Now that $NTLA is officially on clinical hold by the FDA, this is one of the most ridiculously overpriced valuations I've seen.  The stock continuing to trade at $12.50 is insane to me - that's a >$800M enterprise value.

It was as low as $5.90 after the first Grade 4 liver event back in May...Now it is *UP* >100% from those lows *AFTER* having a true Hy's Law event.  This is literally the worst possible non-fatal adverse event the company could possibly have, yet the stock isn't even close to touching YTD lows.

This is, in my opinion, a dead cat bounce thanks to the incredible momentum the $XBI has.  How $NTLA isn't in the single digits is beyond me.

The bear case in the past was that this new class of drug (gene editors) could have unknown long term consequences, and that the diseases they were pursuing already have excellent drugs available to treat them...That long term side effect possibility is still very real, but now we have *ACUTELY FATAL* side effects as another potential hurdle.

Hy's Law cases are an absolute death knell for drug candidates.  $NTLA has one case confirmed, and one near miss back in May already in <500 ATTR patients...This is an extinction-level event for most drugs.

The company will burn through ALL of its current cash in ~1 year from now at current rates.  Who is going to even be willing to dilute them with new cash in an offering when their entire platform is existentially threatened by liver events?

I'm biased by my own position, but this seems like one of the most obvious shorts I've ever seen.

Sure, they have some data coming up in the next couple weeks...that would've been a potentially big catalyst if the drugs were safe.  We now know they aren't.  Who cares if efficacy looks good if the drugs aren't safe enough to administer?

If any *sane* person (you know who you aren't) would like to offer a coherent reason why this isn't deep into single digits, I'm all ears.  IMO it's "look out below" time.

Ok, so time to get serious on $NTLA.  It is going to single digits.

Total operating expenses in 1H25 were >$261M.  That means that at the moment, they would have ~$500M cash.

107.3M shares outstanding means ~$4.66/share is cash value.

BOTH of their lead programs have now had


Summary: Bearish NTLA: >$1B EV unjustified given questionable drug use cases, likely black box warnings, REMS, and fatal hepatitis risk.

@Antifunbw It has to go lower.  >$1B EV for a platform making drugs with questionable use cases and high likelihood of black box warnings, REMS, and fatal hepatitis cases.

Market is irrational.  $NTLA should go much lower, in my opinion.

@A_May_MD Would you still considering shorting with an institution holding up the stock price? Would you consider waiting it out?


Summary: Long QURE as 3rd-largest position; drug near certain approval, premium pricing + massive HD patient demand implies significantly higher stock price.

Didn't tweet much last week as I was spending time with family.  Missed discussing some exciting stuff, especially the $QURE Huntington's data.

On the morning of the data, I made $QURE my 3rd largest position (behind $ABVX and $NKTR).

If the drug is really doing what it *looks* like it is doing against historic controls, then it is one of the biggest medical breakthroughs of my lifetime.  The KOL on the call certainly seemed to think that it is.  Huntington's is a truly horrific disease, and given that there is absolutely nothing for it, a treatment that legitimately alters the disease's course would deservedly be a massive drug.

I definitely get that there is some baggage in terms of historic control design, prior cohorts, AAV risk, etc.  But, again, it's hard to overstate how big of a deal it is if the efficacy signal is real.

And, frankly, as far as the stock is concerned, I think we are past the point of worrying about the regulatory risk of this not getting approved because of critiques over trial design etc.  If there is one thing we know for sure about the current Executive and FDA/HHS adminsitration, it is that they care a lot about IMAGE.  I mean, $SRPT has come back from the brink despite paltry evidence of efficacy and resounding evidence of danger.

I'm telling you, more laypeople are familiar with Huntington's disease than with DMD.  This Huntington's breakthrough is, and will continue to be, mainstream news.   Even more so because the current administration is going to *love* boasting about how the first treatment (which some of them will refer to as a "cure") for Huntington's was approved under their term.

This is going to be a big PR win for the current administration.  And remember that the terms/design of this registrational trial were approved under the PRIOR administration...Do you really think that the current image-obsessed regulators are going to OVERTURN the prior administration's approval requirements in order to REJECT the world's first treatment for HUNTINGTON'S disease?

I do *NOT* see that happening.  I think this drug is as good as approved.  I predict that $QURE (or whoever may end up marketing the drug -wink wink-) will charge a significant sum for it, and the ramp to $1B in sales will be lightening fast...likely limited only by initial neurosurgeon capacity and not by patient demand/TAM, which I expect to be massive (this disease is a gruesome death sentence for middle age adults - they'll want this treatment).

So that was the big excitement I missed out on discussing last week.  I didn't own any before data, but $QURE jumped straight up to #3 for my portfolio afterwards.  The stock has done well since, but if you're like me and see a high probability of approval, premium gene therapy pricing, and significant demand among the large pool of HD patients with no other options...You probably see $QURE going significantly higher.


Summary: Bullish QURE: targeted mHTT lowering mechanism supports patient benefit vs Tominersen's universal approach.

1) mHTT should be ignored as for this disease is is functionally immeasurable.  You cannot differentiate the location where it’s coming from.  It’s useless in this context, on top of being INSANELY hard to measure via assay to begin with.

2) Yes that is important…and likely why Tominersen made patients worse and likely why $QURE could benefit patients since it DOESNT universally lower mHTT…it only does so in the location where mHTT is causing disease…this point is fully in *support* of $QURE

@A_May_MD Regarding point 2:
I think the bear argument is that 1) mHTT measurements were all over the place. they decreased in year 1 measurements and data was noisy/unreported after that. why did they show a big decrease in year 1 if it was isolated to the striatum? I understand HTT


Summary: Bullish on Rezpeg: multiple viable paths to commercial success including post-JAK maintenance setting despite sub-threshold efficacy.

Rezpeg (rezpegaldesleukin) is Nektar Therapeutics (NKTR) pipeline asset

Piper bar of >15% salt reduction delta probably right.  Up a lot if >20%.

Post JAK maintenance angle is super interesting to me.  The side effects on the JAKi label are a huge (HUGE) barrier to indefinite use, and in my experience it’s very consistent that even short interruptions lead to return of disease.  Rock and a hard place for chronic JAKi = poor adoption despite a clearly very large TAM.

If someone with a JAK could get ahold of Rezpeg and pull off that trial (don’t see why they couldn’t), I’d imagine they’d have an SoC regimen.  And tbh that’s arguably a plan that rezpeg could fall back on if it’s active but less than stated above…multiple ways for this to make sense I think

@A_May_MD @Banana_Oncology @lame_karma What’s your bar and do you think it could be a viable drug in post jak maintenance setting if data confirms active but less than low dose jak.


$NTLA is so cooked … $NTLA has a Hy's law death already in <500 patients. COOKED. Absolutely cooked.

Summary: Decisively bearish NTLA: Hy's Law death in <500 patients signals fatal hepatotoxicity risk, making the program uninvestable regardless of FDA outcome.

$NTLA is so cooked

Doesn’t even matter if the FDA ends up letting them waste more money on Nex-Z.

Don’t. Mess. With. Hy’s. Law.

---

Btw, there was “only” 1 Hy’s Law death in this $SNY trial.   1/2700.

0.00037%

Less than one one-thousandth of a percent.

$NTLA has a Hy’s law death already in <500 patients.

COOKED.  Absolutely cooked.

Anyone unable to grasp this needs to be grabbed by both shoulders and vigorously shaken.

---

Oh look who’s back!  Still has me blocked but hasn’t engaged at all since everyone found out about the pedophilia thing.

“Hy’s law isn’t bad if the drug isn’t chronically dosed!”

Lmao.  Braindead cope.

You also can’t chronically take a drug when a single dose kills you! https://t.co/JO3pASHMvo


Summary: NVO should bounce on impressive amycretin data beating semaglutide and tirzepatide on weight loss and A1c targets.

Credit where it’s due - $NVO should bounce today.  Those amycretin data look quite impressive at first glance.

Weight loss and A1c target (<7) rate were both better than not only semaglutide, but somehow also tirzepatide (cross trial comparison caveat).

@Sanctuary_Bio Tyfys $NVO

(Though ngl I’m surprised it’s down *this* much during the healthcare rotation)


Summary: Bearish NTLA: today's bounce on FDA/CRISPR headline is fluff; predicts the pump fizzles quickly.

$NTLA getting a bit of a dead cat bounce boost this morning from this BBG article about CUSTOM gene editing treatments for extremely rare diseases getting support from the FDA.  Just be aware that the article/headline are fluff/inconsequential as far as $NTLA is concerned, and the underlying story there is still dire.

The article discussed the miraculous case of "Baby KJ" who had a CRISPR treatment designed literally *just for him*.  So far the treatment has been successful, and may save his life.

The FDA is now planning on making it easier to treat patients in this circumstance (exceptionally rare genetic diseases with fatal/morbid outcomes getting one-time personalized experimental treatments).  This is FANTASTIC, and exactly what the FDA should be doing.

These small conditions are not commercially viable for traditional pharma to treat, and making them adhere to the same rules as diseases with thousands of patients almost guarantees there will never be treatments for them.

This is what the FDA should be doing, and this is what CRISPR should be used for (at least for the foreseeable future).

$NTLA tried to take unknown treatments with permanent outcomes, good or bad, into diseases with excellent existing treatment alternatives.  This was a mistake, and the company will suffer for it.

I hope that there will be hundreds to thousands of individual patient cures generated from the customized therapies that academic researches can build using CRISPR, like in Baby KJ's case.

As for $NTLA, this morning's buzzy headline that sent CRISPR stocks soaring is meaningless, and I predict that the current pump to the mid $13s is going to fizzle out quickly.

https://t.co/q9S6IZLUxc


Going lower, btw. The company is a cash furnace and IMO they have no advanced stage assets worth investing in. Stock should trade below cash. >50% downside from here just to get to EOY cash

Summary: Short NTLA: cash furnace with no advanced assets, >50% downside to EOY cash/share ~$4.75, out of cash by H1 2027.

$NTLA $9.70s now.  Going lower, btw.

All the data are out.  None of it is pumping the stock.

The company is a cash furnace and IMO they have no advanced stage assets worth investing in.

Stock should trade below cash.

---

Cash at the end of next month will be ~$550M.  ~115.8M shares outstanding.  Current market cap ~$1.15B.

🚨Cash/share EOY ~$4.75 🚨

>50% downside from here just to get to EOY cash, and then the cash incinerating company would be out of cash completely at current rates by late first half of 2027.

Good luck with that.

---

@GeneInvesting

---

@GeneInvesting When $XBI has a face ripping rally day like yesterday and $NTLA just market performs (not up double digit % like a high beta name should be on such days), you know it’s in trouble.

Tick tock $NTLA.  Going lower.

---

@GeneInvesting $NTLA having a rough day https://t.co/QHc7rd7aum


Summary: NKTR deeply undervalued post-SNY failure; now positioned to capture the large post-IL4/13 market unopposed, not sufficiently re-rated upward.

Yeah I really do not understand $NKTR valuation at all.

Sure it has to repeat phase 2, but yesterday “repeating phase 2” would’ve meant fighting it out tooth and nail with OX40 for market share.  Today it means relatively easily gobbling up the absolutely gargantuan post IL4/13 market.

Not even close to sufficiently re-rated.

Understandably failure in $SNY trial doesn't necessarily mean $NKTR Ph3 will succeed. There is always a chance that Ph2 results may not translate into a positive Ph3

But $SNY losing $10,000m while $NKTR only has ~$500m EV now means people is expecting a 5% PoS for $NKTR Ph3?????


it's too high for a consumer goods business with a dying core

Summary: Bearish HIMS: valuation too high for a consumer goods company with a deteriorating core business.

@alc2022 Actually it’s too high for a consumer goods business with a dying core.

3.5 times sales is absurdly cheap for $HIMS


Summary: Sarcastic bullish framing; actually bearish HIMS — federal government threat to its moat is real danger longs are ignoring.

One reason that Trump cannot do this is because it would breach the $HIMS moat.   NOT LEGAL.  You can’t just ignore an impassible moat like what $HIMS has.  I don’t care if this is the leader of the most powerful nation in the world HIMS GOT HERE FIRST SO THEY GET THE MOAT OK?! https://t.co/vZ1LMqrjhi

---

The “what if $AMZN steals the $HIMS moat?!” panic just got upgraded to “what if the federal government steals the $HIMS moat?!”

Didn’t see that coming.  Hoping the longs ignore the obvious danger and take it to the $70s 🤞🏻


Summary: Bullish NKTR as a beneficiary of Nobel Prize in T-Reg research, implying its T-Reg–expanding drug gains relevance.

This year’s Nobel prize in Physiology/Medicine goes to these researchers of…T-Regs!

Does anybody know a company whose drug induced T-Reg expansion? 🤔

$NKTR 😉

https://t.co/3q9ajhUM4J


Summary: Holds a long position in TENX.

@GeneToGreen @Jonny_fun_guy @TweetAwayDK @AaronRosenblum5 @tarrikzaid @blankspacenom @biofeed @pawcio2009 I am long

@A_May_MD @Jonny_fun_guy @TweetAwayDK @AaronRosenblum5 @tarrikzaid @blankspacenom @biofeed @pawcio2009 Are you invested (or do you plan to invest) in $tenx?  Just curious.


Summary: Bullish QURE on open-ended upside despite ambiguity around efficacy review.

@Empiricalcontra $QURE upside is so open ended though, helps even it out.

@A_May_MD Hmm, abvx is a clean Bo. QURE gets approval, but ongoing review to ensure efficacy. Still some ambiguity if it’s actually effective = not a clean bo is my thinking.


Summary: Long NKTR as biggest beneficiary of SNY amlitelimab P3 disappointment; NKTR ~$500M mkt cap unjustified vs SNY losing $12B on competing drug failure.

HUGE news for $NKTR this morning - $SNY Amlitelimab P3 AtD data are a borderline flop.  This was the competitor drug that $NKTR bears were worried about.

$SNY is down $12B in the premarket on the data, while $NKTR sits with a tiny ~$500M valuation and what *might* now be the superior drug.

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$NKTR $SNY - What happened?  $SNY's amlitelimab in P2 had a 29% EASI75 delta, which compared favorably to the ~27% delta that $NKTR showed in P2.  However, in P3, $SNY's EASI75 delta plummeted to only 15% in the Q4W arm (same dosing as the P2) and 20% in the Q12W arm.

On top of the worse efficacy deltas, the P3 read out at 24 weeks instead of 16 weeks in the P2.  Normally the efficacy delta is expected to increase through 24 weeks, so with the efficacy getting worse even at a longer timepoint, it appears that $SNY's P2 had dramatically overestimated Amlitelimab's efficacy.

$NKTR is by far the clearest/biggest beneficiary of this outcome.  They are "fighting" for the patients who have tried and failed IL-4/13 drugs (though as I have previously covered this is a WAY larger population than people realize).  Amlitelimab was CLEARLY their biggest competitor in this space, and now all $NKTR has to do is repeat their P2 data at 16 weeks at a 24 week endpoint, and they'd have a great argument for a superior drug.  In fact, they'd have the *best* drug for IL4/13 r/r patients, which is *without a doubt* a multi-billion dollar market.

See attached the data comparisons of Rezpeg versus Amlitelimab

---

Again, $SNY is down ~$12B right now on this disappointing P3 hit (not even a failed trial!  Just worse than expected).  ***This is nearly 24x $NKTR's entire market cap!***

Why is $NKTR still at a ~$500M market cap sitting on the only phase-3 ready AtD drug with a unique MoA and significant evidence of a potentially better efficacy profile?

$NKTR valuation at these levels continues to make absolutely zero sense to me.  $12B of $SNY's valuation just evaporated, but those atopic derm patients who need different MoAs didn't go anywhere.  Even just 1/10th of that $12B of "disappeared value" going to $NKTR would be >200% upside for $NKTR...just 1/10th of $SNY's lost amlitelimab value!

---

IMO $NKTR should be up huge today.

---

$SNY loses >$10,000,00M

$NKTR gains ~$70M.

Ok. https://t.co/7LwM49EXhG


if this doesn't play out in $NKTR's favor, what are we even doing here?

Summary: Bullish NKTR: internal LLY emails suggest major damages/settlement should go to NKTR; author implies a win is highly warranted.

If all this $LLY internal email stuff is true, it would be INSANE to me that $NKTR wouldn’t get awarded major damages/settlement here.  Like, blatantly ethically *wrong*.

I guess you can’t ever 100% count on legal stuff, sort of like biology…but wow…if this doesn’t play out in $NKTR’s favor, what are we even doing here?

Earlier I mentioned $lly $nktr internal documents and emails If anyone wants to check
- Exs. 15-18, 25, 44-45, 49 in trial brief references,
- Depositions (Kotzin, Do, Franke, Zalevsky on data concerns)
- JSC minutes (Ex 3 in Moorman Decl)
Findings are as follows:
- $lly


Lilly is running actual H2H *trials* instead of 'real world' data p-hacking, becuase Lilly knows they have the better drug (and the *trial* data back that up)

Summary: Bullish Lilly: running rigorous H2H trials, has the superior drug backed by trial data vs competitor's p-hacked real-world data.

@avidresearch Meanwhile Lilly is running actual H2H *trials* instead of “real world” data p-hacking, becuase Lilly knows they have the better drug (and the *trial* data back that up).

@A_May_MD Humiliating to put data with that short of a median follow up in a CV indication. How did their statisticians sign-off on this ?


Summary: Bullish biotech rotation into $XBI and $BBC, aided by expected 10y yield drop to 3-handle by fall.

The #GreatBioRotation could potentially finally be happening 🙏🏻

3 handle on the 10y fields by fall 🙏🏻 🙏🏻 🙏🏻

$XBI $BBC


It is entirely plausible that AMT-130 could affect only the tiny portion of the deep brain where HD occurs...This is an error of our ability to MEASURE the disease, not necessarily our ability to TREAT it...both doses of $QURE saw lowering of NfL in a dose-dependent manner...8% reduction of NfL over a period of time where would would expect to to go *up* likely by 30% or more over that period of time should not be ignored

Summary: Bullish QURE: rebuts bear case on AMT-130; argues striatal-targeted mechanism is sound, dose-dependent NfL lowering is meaningful evidence of efficacy, and propensity matching is valid.

First of all, props to the author of this first time biotech write up on $QURE.  It takes a lot of time and courage to put your stuff out there, but it is an unrivaled way to learn.

Now, there are several things I disagree with in the article, so I'll do my part and perhaps contribute to some of that learning (as I trust others will continue to do for me).

1⃣ One big thing the author already corrected in the article was the narrative that $QURE has hidden sham-controlled data or designed this study in a misleading way.  This is not the case whatsoever, but I have seen the sentiment pop up several times elsewhere as well.  This is key to understand: The FDA guided $QURE on the path to changing this signal finding study that was set to have only a 1 year sham controlled period to turn it into a registrational study.  $QURE has not hidden the sham data...they just aren't useful because the sham was only ever run for 1 year.  You can critique the company's move to turn this into a registrational trial all you want...THEY DID IT WITH AGREEMENT FROM THE FDA.  What more do you want from them?  Should they have raised their own bar?  If you are going to blame anyone here, it is 100% on the FDA, not $QURE.

2⃣ There is a big (and common) misunderstanding around mHTT reduction.  The point posed in the article (and by other bears) essentially says:

"mHTT was reduced by 40% in the Tominersen HD study, and that drug failed.  $QURE hasn't even shown mHTT reduction.  The drug therefore can't work if it doesn't even reduce the target mutant protein as much as a failed drug did."

 Here is the main issue with this line of thought.  mHTT is made throughout the entire brain, but it only *needs* to be targeted in the striatum, deep within the center of the brain.
↪Tominersen was delivered throughout the entire brain, reducing mHTT everywhere
↪AMT-130 is delivered only in the striatum, located deep in the middle of the brain.
↪ The tests to measure mHTT are VERY noisy, and they CANNOT measure mHTT from specific brain regions.  So you can only measure mHTT from EVERYWHERE, not from where it matters (in the tiny striatum).

This means that a drug (like Tominersen) that hits mHTT EVERYWHERE in the brain can show big mHTT reductions in the CSF.  However, a drug like AMT-130 that is only delivered a very tiny portion of the "deep brain" will only hit mHTT in that area...the rest of the brain will continue to make tons of mHTT, and the CSF tests for mHTT will show very little change, if any.

Now, HD is principally a disease of the striatum.  The striatum is where you NEED to be lowering mHTT (*especially* the ultra toxic Exon-1 fragments which are primarily produced in the striatum but not elsewhere).

So, the striatum is where you need your drug to work...AMT-130 is directly injected into it.  Tominersen, a giant olionucleotide molecule, was infused into the CSF and had barely any (if any at all) penetration into the striatum...which is where the disease is actually being caused.  So what if it lowered mHTT elsewhere in the brain?

The point:  Tominersen showed mHTT reductions and AMT-130 didn't.  Sure, but this means essentially nothing, as AMT-130 reaches the part of the brain where it is needed and tominersen didn't.  Instead, tominersen hit the rest of the brain, significantly lowering mHTT...but not the mHTT that is actually causing the disease!  Tomi didn't even reach that part of the brain...

It is entirely plausible that AMT-130 could affect only the tiny portion of the deep brain where HD occurs and show almost no effect on overall mHTT levels...because, again, the rest of the brain that is minimally affected by mHTT will just keep expressing the protein and keep the levels high.  This is an error of our ability to MEASURE the disease, not necessarily our ability to TREAT it.

3⃣ I reject the premise that the $QURE propensity score matching was "cherry picked".  The ENROLL-HD study they matched from had nearly 20,000 patients in it.  For the 12 patients in their trial they matched to 940 patients, or roughly 78 natural history patients per trial patient.  That means that each patient was "matched" based on their background/baseline characteristics to <0.4% of the patients in the ENROLL-HD study...This is how propensity matching is supposed to work.  If you want to criticize their approach, I'd go after using a database without baseline brain MRI data.  But to take a trial patient and only find their characteristics to be consistent with a small ~78 patient sliver from a 20,000 patient sample...that's how this is supposed to work, not suggestive of cherry picking.

4⃣ Let's examine this segment of the article:

"""these numbers just feel too convenient for me. a 75% difference...how wonderful.

if the propensity score model was correctly specified, treated and untreated patients should have similar baseline disease severity. but does a precisely 4-fold difference in disease progression rate make sense for patients matched on baseline characteristics? i doubt it. it suggests either:

-model misspecification: propensity score doesn't adequately balance unmeasured confounders. disease progression rate in early manifest HD is heritable, depends on CAG length, and varies by population.

-baseline selection bias: treated patients may have been enrolled at an earlier stage of disease progression, or with slower progressing genetic backgrounds.

-health profile bias: patients who tolerate brain surgery better may simply be healthier overall and decline slower for reasons unrelated to the drug."""

Well, the author left out one possible explanation for why the study showed that treated patients did better than the natural history studies, and it's an important one...MAYBE IT WAS BECAUSE THE DRUG ACTUALLY WORKS!!!

This portion of the article reeks of a conclusion in search of an explanation.  Failing to even consider the possibility that a drug that knocks down a disease-causing protein exclusively in the portion of the brain where the disease occurs could actually be working...not good analysis.

There are plenty of career-long HD experts who think this natural history comp is a strong sign of activity...they aren't idiots.  It behooves us to consider that this drug is actually working, especially given the above discussion about how endpoints like mHTT lowering could be totally useless even in a drug that is effective.  Coming to a conclusion and working backwards to support it is not good practice for anything, but especially in biotech investing.

5⃣  There's a section here that compares Tominersen's 40% mHTT lowering with $QURE's 8% NfL lowering and determines that if 40% on mHTT wasn't good for Tomi, then 8% for NfL can't be good for $QURE.

This part is off the tracks a little - that's a totally irrelevant and useless comparison to draw any attention to between two unrelated labs.

However, there is a useful point to make here on mHTT and NfL (neurofilament light chain - a marker of brain degradation - higher NfL is WORSE)...

➡Tominersen lowered mHTT by 40% (again, because it hit mHTT all throughout the brain, likely except for the striatum where it's needed).  But patients got worse, not better...and tominersen saw NfL levels RISE in the study!
➡$QURE is not seeing mHTT lowering (again, because they're only hitting it in the tiny portion of the brain that matters, allowing the rest of the brain to keep making it)...and $QURE showed dose-dependent LOWERING of NfL over the course of 3 years.  This is highly unexpected, as Huntington's patients are expected to have NfL rise consistently over time - especially over 3 years...but both doses of $QURE saw lowering of NfL in a dose-dependent manner...

So...
↪the drug that DOESN'T hit the striatum where the disease occurs (Tominersen) DID measurably lower mHTT, but saw NfL RISE...because they were hitting mHTT in the wrong places.  The drug showed no sign of clinical benefit.
↪the drug that DOES hit the striatum where the disease occurs (AMT-130) DID NOT measurably lower mHTT, but saw NfL LOWER...*maybe* because they're actually hitting mHTT where they need to, and preventing brain degeneration as a result...

8% reduction of NfL over a period of time where would would expect to to go *up* likely by 30% or more over that period of time should not be ignored.  This is a direct marker of brain degeneration, and unlike clinical endpoints, is not highly susceptible to open label biases (I don't think patients are likely to be able to reduce the NfL levels in their brain via placebo effect)...

This part seems pretty simple to me:
...the drug (tominersen) that lowers the LAB MEASUREMENT of mHTT but not the striatial measurement of mHTT made patients worse and NfL levels showed that
...the drug (AMT-130) that does not lower the lab measurement of mHTT but might lower the STRIATAL measurement of mHTT seems to be making patients better, and NfL levels show that...

Anyway, again, props to the author of the article.  Great way to learn and IMO they will go far if they keep it up.

$QURE thank you for the patience everyone, had to learn how to use substack. my first ever write up on uniQure and their HD asset AMT-130 is live now!

 https://t.co/z40kO8lAMz https://t.co/Xiki2FaGYj


Summary: Bearish NTLA; crushing news for longs signals dark times ahead.

Hahahahahaha it actually *was* the single worst investor of all of our lifetimes who was propping up $NTLA today (like I suggested)!

Unbelievable.  Absolutely *crushing* news for $NTLA longs.  🤣 https://t.co/flNeEQnYv2

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Dark times ahead $NTLA


Summary: Bullish XBI to triple digits this month on biotech rotation driven by slowing inflation and falling jobs.

Coldest PPI we have seen in a while and jobs revised down by a whopping 911K yesterday.  Inflation slowing, jobs falling.

Biotech rotation is just getting started.  I predict $XBI back to triple digits at some point this month 🫡
$XBI $BBC

---

The macro indices are green on this news premarket too, because “rate cuts bullish!!!!”.  But, at a certain point inflation slowing so much *because* jobs are so slow is not actually good, and the major indices take this sort of thing as *bad* news…that’s when biotech really gets its rotation, IMO.

The “generalist tech only goes up!” mantra needs to die at least a little for biotech to flourish (again, IMO).


I am currently long (and bought more this morning)... At ~$1.70 currently I actually expect continued upside for $PALI even though you could've had it for <$1 only last week!

Summary: Long PALI, bought more; expects continued multi-day upside from ~$1.70 on strong PDE4i validation and unique gut-restricted MoA with no US competition.

THIS IS 🚨NOT🚨 A PITCH, but the $PALI story is a fascinating one, and I am currently long (and bought more this morning).

This is a wild story of a nanocap biotech that was valued at ~$8M only a few days ago, but has now burst onto the scene with a potentially unique approach to an increasingly validated target in IBD and >40x'd its "value" (a number which I think will likely continue to balloon today ).🎈

People will compare it to $ABVX given that both have QD oral treatments for IBD, but let's break down the specifics of the nascent $PALI story...

---

First...❓How did a seemingly left-for-dead ~$8M company raise $138M seemingly out of nowhere❓

Well, some keen observers noticed that on 10/6/15 (today) there was going to be a presentation of new data from a Chinese company testing their drug (Mufemilast) in UC.  That presentation was a "prestigious" late-breaking presentation, placed immediately after highly anticipated data from...none other than $ABVX!

The tea leaves suggested that this meant the Mufemilast trial data were positive.  This was important because $PALI's lead candidate has the same MoA as this Chinese drug (Mufemilast)
➡PDE4i

Furthermore, one could look back at old data from 2018 where another PDE4i, apremilast (AKA Otzela) had shown signs of efficacy in UC.  This further strengthened the idea that Mufemilast could positively validate $PALI's target.  (More on the apremilast PoC later).

So, investors piled into this nanocap biotech in order to invest ahead of potentially validating data from a Chinese drug with the same MoA, raising $PALI's market cap from ~$8M to ~$330M in less than a week! 🤯

---

Today, the Mufemilast UC data came at an early morning presentation in Berlin.

The numbers are...impressive, to say the least.  We will of course have to make note of caveats like small n, all overseas (China) patients, a milder/less refractory treatment population, etc.

BUT, just looking at the raw numbers, there is a *lot* of room for the data to get worse and still have a meaningful drug in UC.

Take a look at the table I built for $ABVX and updated with these data for more detail, but the highlight for Mufemilast/$PALI is...
👉A 44% clinical remission delta at the high dose!

This is an absurdly high number...it's  >double the CR delta of the mean/median UC drugs on the market right now.  Again, caveat emptor, but the data are impressive for what they are.

Importantly, I suspect that these mufemilast data have exceeded the bullish hopes/expectations of the large funds who just invested in $PALI awaiting their release.

Accordingly, I do expect $PALI to continue its recent move upward today.

---

$PALI
I know, I know.  "The mufemilast data are all Chinese and small sample size!  We can't trust that this validated PDE4i for UC!"

Well, again, the mufemilast data could actually be WAY worse and still be positive, but beyond that, we actually already had pretty good validation for PDE4i in UC *before* the new data this morning!

Let's review the story of apremilast (Otezla) in UC:

➡Otezla was approved for psoriasis way back in 2014, and it was a big success.

➡Then, in 2018, seemingly impressive data for Otezla in UC were published!  Let's review the highlights...
      ↪65% clinical response with a 38% clinical response delta (compare to 31% delta in $ABVX P3)
      ↪36% clinical remission with a 17% clinical remission delta (compare to 16% delta in $ABVX P3)

So, these largely forgotten Otezla data from a trial that started a decade ago had actually already set a pretty strong precedent that $PALI's and Mufemilast's PDE4i MoA could be good for UC...

⏸BUT!  Despite those very strong numbers, Otezla never moved forward in ulcerative colitis...Why⁉

---

$PALI
Why would $BMY have failed to develop a clearly promising drug in UC for a drug that was already a blockbuster in psoriasis?

Well, one argument would be that the Otezla data actually weren't that impressive, and there was some hole in the data that turned $BMY off of developing the indication further.
      ➡One piece of evidence that supports this bearish take is that the endoscopic data were NOT as resoundingly positive for Otezla.
         ↪Otezla hit on the MEC endoscopic response endpoint, but missed on endoscopic remission...

🤔Does this remind you of anything🤔
      👉How about the $MORF story, where promising P2a clinical response/remission data ultimately flopped, and the red flag that predicted failure was...poor endoscopic data!

That said, $MORF is not a great comp, as their data were much smaller n and unblinded.  The Otezla data were much more robust in trial size, design, and outcomes.

Fortunately, there are 2 better explanations to show us why $BMY failed to develop what looks like a clearly promising drug:
   1⃣Patent life was questionable for Otezla.  The drug had been approved 4 years before the P2b UC data were published...From that point, it would likely take another ~5 years to get the drug to market in UC.  The cost/time and minimal remaining patent life likely turned $BMY off of this opportunity, despite positive data.
   2⃣Perhaps most importantly 👉In retrospect, we now know that $BMY was actively in discussions to acquire $CELG at the time these Otezla data were presented.  This deal not only brought in a competing UC drug (Ozanimod), but it also forced $BMY to divest Otezla (ultimately to $AMGN) due to CoI with Deucravacitinib
      ↪So, why would $BMY invest in huge trials for a drug they not only have patent life concerns about, but which they *knew* they were going to have to get rid of if their $CELG deal went through?

These factors explain why $BMY abandoned Otezla in UC, and debunk the idea that the drug wasn't taken forward due to some unknown problem in the data, strengthening the rationale for $PALI targeting PDE4 in UC.

BONUS:  Want to be extra certain that Otezla wasn't taken forward in UC due to problems with the data?  Check out this X conversation from 2018 including multiple world-leading UC KOLs chiming in on their shock and disappointment that Otezla was being canned!  (Now THAT is some "Twitter alpha"!)
➡David Rubin was the KOL on the ABVX P3 call!
➡Silvio Danese just presented the $ABVX data at UEGW this morning, *and* was lead author on the Otezla UC publication!

These IBD docs all saw the Otezla UC data and were "shocked" and "disappointed" when they learned that the drug wasn't taken forward in UC...Then, due to patent/M&A circumstances the drug was discontinued and we all forget about the target for 7 years, until now!

---

Now, as far as what $PALI has and how it should be valued...

Their drug is PDE4i just like apremilast and mufemilast, which have now both shown resoundingly positive efficacy in UC.

However, the caveat is the $PALI has a unique addition to its MoA to hopefully make it *gut restricted*.

Basically, $PALI adds a sugar group onto their PDE4i drug that can *only* be cleaved by bacteria located in the gut!  The idea is that the drug is inactive when it is blocked by this sugar moiety, but when the drug arrives in the gut, the local bacteria chop that sugar group off and it will work only in the gut where it is needed!

Ideally this MoA will lead to equal/greater efficacy with fewer side effects (off target effects of PDE4i include diarrhea, nausea, headache, and a questionable suicidality link).

*If* $PALI can show a superior outcome with this proprietary design, the drug would be huge (though it doesn't have to be better to still be a huge success).

It is early for $PALI, but P1/P2a UC companies with promising MoAs have held huge valuations in recent years, with the poster child being $MORF fetching a $3.1B valuation despite only having small n open label P2a data WITH a questionable endoscopic response result...Again, it's early, but a similar valuation for $PALI once they get to that stage would currently be ~$15/share.

And based on how strong the PDE4i validation is at this stage, I would expect PALI's P2 data to look better than $MORF's did.

Obviously the other value comp people will point to is $ABVX (likely to end up >$10B), but of course, getting the post-P3 stage successfully will take a lot of time and risk.   Still, this is illustrative of how much upside there could still be for $PALI in the long run despite its rapid rise in market cap over the last few days!

---

$PALI
So, in summary, the validation for PDE4i is now *extremely* strong, and $PALI has a unique approach to targeting it with minimal (no?) competition against them here in the US.  At ~$1.70 currently I actually expect continued upside for $PALI even though you could've had it for <$1 only last week!

We've all seen how totally reinvented/exciting storylines in small cap biotech can yield multi-day multi-x movers.  IMO that's likely what we have here - TBD!

I also want to give shoutouts to:
➡ @AaronRosenblum5 who had posted about $PALI *before* it was on people's radar
➡An anonymous X account who played a central role in this whole story developing

Nice work!


why *EVER* take the risk for a gene editing drug that *might* make it so you don't have attacks anymore (*MIGHT*) when you could just take $PHVS prophylaxis and/or $PHVS on demand treatment

Summary: Bullish PHVS as superior HAE treatment vs risky one-time gene editing drugs; prefers its prophylaxis and on-demand options.

Truly silly.  Why *EVER* take the risk for a gene editing drug that *might* make it so you don’t have attacks anymore (*MIGHT*) when you could just take $PHVS prophylaxis and/or $PHVS on demand treatment when you start to notice a *very* rare breakthrough attack starting up.

Insane.

@A_May_MD My favorite part of the bull case was
1 time treatment* or hundreds of injections

*might kill you


the TAM is going to grow with the first therapy approved ($QURE's)

Summary: Bullish QURE: underdiagnosis of Huntington's will expand TAM as first approved therapy drives diagnosis rates up.

@plainyogurt21 Horrifying.  The “knowing what’s going to happen to you” element of this disease is diabolical.  I do believe that this leads to underdiagnosis of early disease and that the TAM is going to grow with the first therapy approved ($QURE’s)

@A_May_MD Did the exact same as soon as it reported. I’ve seen patients who tried to kill themselves with HD…..because they’d seen their parents die slowly and kill themselves at the end. This disease is common, debilitating, and drugs are NEEDED


$ABVX showed a higher remission delta than every single injectable on the market. It's just a better drug.

Summary: Bullish ABVX: higher remission delta than all injectables plus oral delivery advantage makes it a superior drug.

@charle77238 @TTRAmyloid Numerous, but for starters, $ABVX showed a higher remission delta than every single injectable on the market.  It’s just a better drug.  The pitch isn’t just about being an oral (though that certainly doesn’t hurt).


Summary: Bullish on Tarsus/UC asset: M&A multiple of 3x is too low given indication expansion potential, implying more upside.

Tarsus Pharmaceuticals, Nasdaq: TARS; M&A/indication expansion context

@marvin_skora Yes I think that’s a good peak estimate for UC but that multiple is low for an M&A multiple especially given the real potential for indication expansion

@A_May_MD Thank you!

Peak sales likely to be at ~3bn USD T UC…. Multiple around 3x would still give a lot of upside…


Summary: Bearish ABCL: OX40L drug is NPV-negative, now worth less than zero.

$ABCL OX40L drug that was worth $0 yesterday is now worth even less.  NPV negative asset.

Also RIP to $IMA that just reverse merged into $IKNA.

$SNY $NKTR $CRVS $APGE $AMGN


Summary: Re-entered short NTLA above $11; targets below $5 on fatal liver toxicity in ATTR study.

Well, $NTLA killed him.

Like I said way back in May, shut this company down.

Re-entered short >$11, which is absolutely INSANE that the market allowed me to do this.

$NTLA should be below $5.

STOP giving highly experimental treatments to people with treatable conditions!!!

$NTLA $BBIO $ALNY $PFE $IONS

$NTLA with scary liver enzyme elevation signal in their ATTR study.

Seriously…Grade 4 means elevation beyond 20x the upper limit of normal (!!)

Shut this nonsense down.

$NTLA running a study here that is unnecessary with stabilizers and


Summary: Bullish XBI small-cap biotech on LLY CEO comments; bearish VKTX (dump signal from same catalyst), already ahead of the move.

Pretty sure $LLY Dave Ricks just told me to lever up on small cap biotechs 🤷🏻♂

$XBI 🚀 https://t.co/mYjp8X4eCP

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Pretty sure $LLY Dave Ricks just told me to dump $VKTX 🤷🏻♂ https://t.co/PBwSFrPWqn

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One step ahead of you this round, Dave 🫡
$VKTX


Summary: Long ABVX: author endorses the quoted thesis that PoS is underestimated by market with 10x+ upside potential.

I won't share in depth pitches like $NKTR often (2/year?).  Only with really compelling setups.  I've got another one now.  The market says PoS is VERY low and that upside could be 10x+.  Like with $NKTR, I think the data say success is far more likely than the market thinks.


Summary: NTLA is severely overvalued above $5; cash furnace with fatally flawed platform, lead programs dead, implied near-zero valuation.

Don’t start with “risk mitigation” BS for $NTLA.

What program do you propose???  This patient died IN THE HOSPITAL.  What more could be done?

This program is over.  The platform as it currently exists should be too.  ATTR is a zero.  HAE is a zero.

Stock trading >$5 is severely detached from reality.  The company is a cash furnace with lead programs that cannot be taken forward and a platform that may be fatally flawed no matter what indications they take it into in the future.


Summary: Still long PALI and added significantly; views it as cheap.

@Neon68 Yes have added significantly. Cheap

@A_May_MD Any updates on $PALI? still long?


Yes, I am short $NTLA. It is going to single digits. Cash per share by the end of the year is in the $3s.

Summary: Short NTLA to single digits / ~$3s cash/share EOY; both lead programs effectively dead after Hy's law G4 liver events, no pipeline replacement.

Ok, so time to get serious on $NTLA.  It is going to single digits.

Total operating expenses in 1H25 were >$261M.  That means that at the moment, they would have ~$500M cash.

107.3M shares outstanding means ~$4.66/share is cash value.

BOTH of their lead programs have now had G4 liver events, with today's event also having elevated bilirubin.  This means Hy's law was met.  If you don't know what that is, read up.  This is OVER.

These programs should be stopped, as both HAE and ATTR have multiple SAFE and highly efficacious treatment options.

Hy's law tells us that if they move forward (and somehow get the FDA to approve) with these drugs, they are going to kill someone.  This is NOT ACCEPTABLE when the diseases already have safe/effective treatment options.

This was a cool science experiment, but we are done here.

Cash per share by the end of the year is in the $3s.  They have no advanced-stage drug candidates to replace these now dead lead programs (HAE and ATTR).  It doesn't matter how "good" the efficacy data from these programs looks at upcoming updates.

These drugs are. not. safe.  The risk/benefit here is not acceptable.

IDK if it is Cathie Wood or some other ignorant trader who pushed this to the $16s this morning, but it's not going to last.  The stock is currently up >120% from where it was in June, with the only news between now and then being today's *Extremely* negative update.  Ridiculous opportunity.

Yes, I am short $NTLA.


Summary: Sarcastic: LLY's $1B deal is trivial vs tirzepatide cash flow, implying LLY remains M&A-capable and bullish; genuinely congratulates VTYX longs on the acquisition.

Oh no $1B!!!!  $LLY is now out of M&A Capital for several years, as this represents multiple HOURS of tirzepatide revenues 😱😱😱😱😱

(Congrats $VTYX longs!!!)


Summary: Expects ABVX to follow VRNA's pre-buyout run-up pattern over weeks to months.

@ag76_biotech Exactly what $VRNA did.  I personally expect $ABVX to do the same.

(I’m biased, although I was for $VRNA as well and called that one correctly, so 🤷🏻♂) https://t.co/2iFkuAMCu5

Buyout run up has started for $abvx, note how stock is up every day 2-3% for no reason, this pre buyout run up can last from few weeks to few months


Summary: Bearish NTLA: repeated fatal liver toxicity events make the lead drug a dud facing a black-box warning vs competitors with zero fatal side effects.

They had liver tox during P1s dose escalation.  They went with a lower dose because of it.

They had a G4 liver tox event early in P2.

They now had a G5 liver tox event in middle of P2.

Sure the FDA could allow them to continue the trial.  Totally possible, if stupid.

Worrying about that alone is naive and myopic.  The FDA does not weigh in on commercial viability *at all*.  They’ll gladly approve a drug that will do $0.00 in sales.  That is not their concern or jurisdiction.

That is the situation $NTLA is in.  Even if they got approved someday, they’ll have a black box warning for fatal liver toxicity versus a stable of effective drugs with ****ZERO**** fatal side effects.

The drug is a dud. Further development is a waste of money and a risk of further deaths.  Safety is paramount.  If you pretend you can’t understand that then I can’t help you 🤷🏻♂

@A_May_MD This is exactly what I’m talking about. It IS a complex situation. One that the fda will weigh in on and help clarify. We don’t even have data back on the patient. Yet you have drawn conclusions.  Your thesis may be end up correct but it won’t be b/c of your analysis.


Why it doesn't trade to all time lows is beyond me… Hy's Law case treated with such grace as $NTLA got today… That already questionable R/R skew just got hit with the grim reaper of drug development AEs

Summary: Bearish NTLA: Hy's Law case should have driven stock to all-time lows; current >$1B EV seen as irrational given safety risk and available alternatives.

“Oh my god.  He admit it!”

Tony admits he got MNPI on $NTLA and disclosed where it came from on his spaces 😂

1) Get MNPI
2) Post it on X pretending it is just a random prediction
3) Get called out for blatant MNPI when the news comes out
4) Deny it for a few hours
5) Admit to it and disclose your source a few hours later

Actually, sincerely unbelievable.

https://t.co/a91HCZ5V7H

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Aaannnyway, more productive discussions ahead.  Enough with the side story.

Have had the discussion with multiple people today that I/we have never seen a Hy’s Law case treated with such grace as $NTLA got today (still trading at >$1B enterprise value and well above yearly average trading price).  Really bizarre from my perspective.

Sure, we are in a bear market, but Hy’s law stands alone as the ultimate bogeyman in drug development.  That’s on top of the $NTLA bear thesis having always been that safer effective treatments are readily available for these diseases.

That already questionable R/R skew just got hit with the grim reaper of drug development AEs…

Why it doesn’t trade to all time lows is beyond me, but hey - markets can be irrational!

I certainly have my biases as well…still, if you’re brushing of a Hy’s Law case as no big deal, you might want to look into your biases as well!

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I got so used to typing “bear market” that I literally can’t stop…might have even been autocorrect - even iOS doesn’t comprehend biotech being in a bull* market 😅 $XBI $BBC


Summary: Bullish AA: stock is too cheap even without the AtD catalyst; AA is a call option on top of an already undervalued base.

Idk, it’ll be up a lot if it works, but I’ll work on the numbers more when Dec comes around.  Would be more important to me if it weren’t my opinion that the AtD opportunity is currently severely mispriced.  AA is a nice call option in my book, but even without it, my opinion remains that the stock is too cheap.

@A_May_MD What do you think is the stock up/down on this trial? Feels like people don't want to own it ahead of the data - on the other hand a miss is a miss

@A_May_MD
@seedy19tron


Summary: 33% chance of reversal but asymmetric upside skews risk/reward positive; implicitly bullish.

@btcbabey 33% but big upside on that skews + r/r

@A_May_MD What chance do you think qure gets reversed? Im at 65%


Summary: Bearish NTLA: ATTR program worthless due to permanent safety-issue stigma vs. safe competitors, regardless of whether FDA halts trials.

Give me an example of what you think I was wrong about but didn't admit?  Just more made up nonsense from you trying to pick fights.

I do not accept your offer to bet that $NTLA will not be allowed to resume their trial, because I do not think the odds of the FDA shutting the trials down completely is high enough for such a bet.

It's entirely possible the FDA allows the study to continue.  My assertion has always been that it is over for Intellia in ATTR because these safety issues are now a permanent black mark on the drug that will now have to launch as an unsafe option against safe treatment alternatives.  The studies can continue and the drug still end up worthless.  That is my stance.

Nothing more, nothing less.

Although I believe that the FDA *shouldn't* allow the studies to continue, it is not necessarily my assertion that they *won't*.

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@RNAiAnalyst @Cattletech No examples Dirk?  Why are you always calling me out for stuff that you can't back up and then just ghosting me when I respond to it?


Summary: Bullish ABVX: oral drug's Phase 3 remission delta beats every biologic on market, exceeding the bar needed for commercial success.

@financebully @PCM_bio That’s right, it doesn’t have to be more effective….And yet the $ABVX P3 clinical remission delta is higher than every biologic on the market 🫡

@PCM_bio agree. oral is a huge deal and they don’t necessarily need to be as effective as biologics as long as they’re as safe/safer.


Summary: Bearish NTLA; mocks bullish rationalizations of patient death — Hy's Law criteria all failed, safety risk is severe.

Seeing some record setting dumb takes on $NTLA.  Excerpt below with some additions:

“Hy’s Law is bad if…

1) chronically dosed ***(the patient died from a single dose)

2) not transient ***(I’m hearing early reports that the patient’s death may in fact be long lasting, if not permanent)

3) mitigation doesn’t work ***(the mitigation didn’t work…the patient died in the hospital after having had weekly lab monitoring to begin with)


Summary: Bullish NKTR: repeating P2 data now clinches 2L market lead post-SNY failure; market has not priced this in.

@pick1998_2 that was already a risk before.  Now simply repeating P2 data means taking the lead in 2L market, whereas before it meant still having to fight it out with OX40.  Huge shift and the market has absolutely not priced it in appropriately.

@A_May_MD the main uncertainty is how the good phase II data will be  repeated in phase III. if $sny could fail to repeat strong data, how about $nktr?


This is the profile of a gargantuan drug. A thing of beauty! $ABVX's march to buyout, IMO, continues full steam!

Summary: Strongly bullish ABVX: obefazimod data at UEGW shows universal efficacy, clean safety profile, no friction for prescribers, unique MoA — buyout thesis intact.

$ABVX data at UEGW today showing it simply works in everyone, no matter what they've been on before.  Stat sig broken out into every one of these small n subgroups...

Obefazimod is a *beautiful* drug and GI docs are going to hand this out like candy.  There's just nothing you have to worry about, zero friction.

Once daily, oral drug, no major safety concerns, *no lab/imaging/screening requirements* (huge deal), and no concern that any particular type of patient doesn't respond.

Your patient may have failed everything or nothing...doesn't matter, you can simply put them on obefazimod without a 2nd thought and not have to do anything but write the Rx...

This is the profile of a gargantuan drug.  A thing of beauty!

Oh!  And there aren't any other drugs with this MoA anywhere.  This just doesn't happen anymore in modern biotech.  $ABVX's march to buyout, IMO, continues full steam!


I think some news here should be imminent. And I'm no legal expert, but how anyone could read/understand what went down here and *not* think that $NKTR was wronged and is owed *something* in damages is beyond me…

Summary: Bullish NKTR: imminent trial news expected, author believes NKTR was wronged and will receive damages.

This + $LLY removing counterclaims against $NKTR since close on Friday…I think some news here should be imminent.  And I’m no legal expert, but how anyone could read/understand what went down here and *not* think that $NKTR was wronged and is owed *something* in damages is beyond me…

$NKTR According to judge Donato's calendar, the pre-trial conference is now set for Oct. 14. Let's see if that date holds. This is the last major planning meeting before the trial begins and the very last attempt by the judge to encourage to settle before the trial.


Summary: Bullish ABVX with a $180+ price target in mind.

@A_May_MD I guess you had ABVX for 155 in your mind

No worries boss .. You have free pass from BioX retail.

Keep the good work to make us all rich.


I quite like the idea of generalists getting interested in it… one of very few names that will ultimately work out well for them

Summary: Bullish QURE; expects it to be one of the rare biotech names that works out well for generalist investors.

$QURE is actually a biotech name that I quite like the idea of generalists getting interested in.

Mostly because I think it’s one of very few names that will ultimately work out well for them and keep them coming back for more 😅


Summary: Short NTLA: $1.7B valuation with ~1yr cash runway, pipeline gutted after HAE/ATTR culled.

@MartinShkreli @gmt9992 >$1.7B valuation and a cash pile that is gone in 1 year at current burn rates with nothing advanced left in the pipeline now that HAE and ATTR must be culled.

Ugly doesn’t cut it - this is hideous.  $NTLA is a glaring short here IMO.


Summary: Bullish PALI: visible big-fund filings already large but ~half of total positioning still hidden via pre-funded warrants, implying substantial undisclosed demand.

What’s interesting about the flurry of filings for $PALI is the fact that we’re seeing this number of big positions being filed with such a small share count denominator for calculating % ownership.

Why does that matter at all?  It means there’s a huge chunk of PFWs out there (likely ~90M by my math).

Those PFWs literally only exist to prevent big positions from showing up on paper, and yet…we are seeing lots of big positions being filed on paper!

So even though we are seeing filing after filing of big time ownership by funds in $PALI…a HUGE amount of the $PALI positioning is still hidden…nearly half of the ownership of the company, in fact.

$PALI with one of the hotter post-deal filing sessions I’ve seen lately.

I get the sense that some assumed $PALI was a sort of BS pump job, but I really don’t think that’s the case.  Legit buyers.

That’s mainly why I wrote about it - only in biotech do you have an $8M nanocap


Summary: Long NKTR: still massively undervalued vs AtD opportunity with OX40 overhang cleared; expects continued re-rating from current all-time-post-rebirth high.

$NKTR logged its 3rd straight double digit % increase following this news.  IMO (remember - I'm biased) it is still not even close to properly re-rated.  There is some bizarre psychology around being burnt on a stock in the past that prevents people from realizing the (IMO now glaringly obvious) value of a new drug with a totally different history/mechanism/indication.  It is increasingly easy to view Rezpeg as a potential blockbuster drug, yet the stock's value does not even come close to representing that.

It's taking the market a lot of time, but IMO $NKTR has a long way to trade up before the AtD opportunity is appropriately priced in now that the OX40 clouds have cleared significantly.

The stock closed at its *literal* high of the day (and all time high since its post-bempegaldesluekin rebirth).  Again, I'm biased, but I think that momentum absolutely *should* keep going.

HUGE news for $NKTR this morning - $SNY Amlitelimab P3 AtD data are a borderline flop.  This was the competitor drug that $NKTR bears were worried about.

$SNY is down $12B in the premarket on the data, while $NKTR sits with a tiny ~$500M valuation and what *might* now be the