LT power of compounding. My posts aren’t advice.
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Reflecting on the chat today, I think investors are still missing what $NVCT owns in NXP100 & why I see >3x upside over next 12 months.
NXP100 is technically a pre-phase 3 US drug, but Haisco has already completed two successful phase 3 trials in China, while $NVS has completed two phase 3 trials with Fabhalta, it’s very close chemical analog. Across all 4 trials, efficacy and safety have been remarkably consistent and very strong. NXP100 also appears to have significantly improved pk/pd, supporting once-daily dosing and potentially improved efficacy in some indications, such as IgAN.
Importantly, the Fabhalta studies were ~half Asian and the FDA note no meaningful efficacy differences across racial/ethnic groups. That should matter when potential BD partners (hint: $AZN who is at risk to losing Soliris C5i franchise added in $39 billion Alexeon deal) assess the probability of success and how heavily to discount the existing Chinese data (Hint: very low discount).
PNH is already a roughly $5B market and could approach $7B+ by 2030. Given the unusually high POS here, I think BD valuations for NXP100 today could easily support 3x $NVCT current $700M enterprise value, while assigning essentially zero value to the cancer pipeline.
$NVCT has already 3x YTD. I wouldn’t be surprised to see another 3x over the next 12 months based solely on NXP100 BD value.
So many value enhancing catalysts to this target, as $NVS & Haisco release data on additional indications, like IgAN, myasthenia gravis, dry AMD, & Lupus that could expand Complement Factor B to a $10-15B TAM.
Takeaways from $NVCT Cantor investor conference fireside chat —
Nxp100 — preparing to meet with FDA & assume they’ll run two US PNH studies in treatment-naive & C5 pretreated patients (~35 patients/arm) likely starting simultaneously in 1H27.
PNH efficacy data is extremely compelling, where NXP100 increased hemoglobin 5 g/dL vs 2.2 for soliris, w/ 60% of patients w/ hemoglobin > 12 vs 8% for Solaris. Safety profile is “remarkably similar” & efficacy comparable to slightly better. That raises the possibility that the improved pk/pd isn’t just providing once-daily dosing versus Fabhalta’s 2x daily, but could actually translate into better efficacy.
With that in mind, IgAN could become especially interesting as Haisco’s phase 2 showed ~57% reduction in proteinuria w/ a 3-point increase in eGFR, which is in ballpark of APRIL/BAFF data. Haisco phase 3 IgAN trial should read out data 1H27.
gMG is the next indication mentioned that is being considered after PNH. $NVS is doing most of the derisking for them with data expected in 1Q27. $NVCT will prepare a gMG study but won’t start it until they see the Fabhalta data.
$NVS is spending a lot on Fabhalta developing it across multiple indications, while Haisco is generating additional NXP100 data in China. Positive Fabhalta/Haisco NXP100 results in areas like gMG, Lupus and dry AMD provide NVCT w/ a roadmap for where to invest next.
The balance sheet was noted to be sufficient to execute the current plan through 1H29, including funding two studies in PNH as well as studies in gMG and another additional indication, and phase 1b studies for NXP200 and NXP900 studies. In this context, it was mentioned that NXP900 recently launched a combo study with $PFE lorlatinib in ALK+ NSCLC. For NXP200, management mentioned that they plan to begin a phase 1b study in CNS and will potentially add addional studies in other tumor types following data from Haisco’s 100-patient phase 1B, which reads out in 4Q26. I’d note that CRC is probably a high priority indication, as the Salt form pilot study showed tumor shrinkage in 4/5 patients, with two PRs showing >50% shrinkage and a third patient with -27% shrinkage with durability > 12 months.
sqps.onstreamsecure.com/orig…
Jordan Alexander retweeted
I believe there's a high % chance $QURE gets its approval. Stuff like this from the FDA, in my eyes, further strengthens that belief.
They want to generally make the review criteria more clear, more patient (advocacy) focused, and more flexible about what evidence is reasonably attainable. Not lenient for the sake of being reckless, but because there are situations that warrant different criteria.
I think it would be quite incongruent to be vocally advocating for these new policies (which are suspiciously similar to the QURE debacle), while simultaneously crushing a high-profile drug approval like AMT-130. Incongruent doesn't mean it can't happen, just that it seems like the tail outcome.
"The new framework is intended to enable patient input at earlier stages and at milestones throughout the development and review process. It also aims to provide greater clarity and consistency to drug developers on regulatory decision making. The agency said in a statement that it should take into account what evidence is reasonably attainable, given the nature of rare diseases."
To be clear, FDA officials denied that the initiative was motivated by the earlier controversies. The connection to AMT-130, and the positive read-through, is my interpretation.
"In an interview, senior officials at the agency denied that the initiative had anything to do with the earlier controversies"
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Disclosure: Creek Drive and its affiliated funds holds positions in QURE. Views expressed are current opinions for information only, subject to change and are not investment advice or a recommendation to buy or sell any security. Investing involves the risk of loss and past performance is not indicative of future performance. See the disclosures link in my bio for more important information.
FDA is transforming rare disease drug approvals. The new Rare Disease Framework Initiative will work to give patients more voice, give developers more clarity, and eliminate surprises in the regulatory process. bloomberg.com/news/articles/…
Jordan Alexander retweeted
$qure $clpt
Data is data, definitely much different than the headlines or perception of these 4 year results. People should be shouting from the rooftops on what they just truly produced. It really isn’t very complicated and therefore I would have to hope the FDA could clearly see what has happened. I can’t say I am super concerned that the FDA will not see the same thing.
I know this might sound like an insane take, Uniqure has come much closer to truly halting the disease of Huntington’s than anyone can truly imagine. This is why Victor Sung says, well, my 6 patients that are now over 5 years are still stable. Same with the rush patient. These are factual statements.
Why? Because they are stable, we just saw that, TFC got better in year 4.
Does the FDA agree or disagree that TFC is the most important thing to track in HD? The literature and recent conversations with the FDA agree with that statement.
Jordan Alexander retweeted
$qure $clpt
Serious question here, how do we explain the exact starting point track hd tfc 12.2, amt 130 was 12.2 on the high dose starting.
2024 decision modeling analysis using TRACK HD data estimated a 36 month TFC change of −1.989 for the TFC 11–13.
AMT-130 high dose: −0.27 tfc at 36 months, n=15
We can agree this isn't 100% like for like, but the starting TFC is remarkably similar, and the populations are in a comparable early functional range
You have that plus the 2000 study of 575 patients with baseline showing per year 0.97 points loss for tfc 7-13. Check out all the studies below.
Historically, patients with higher baseline TFC have generally shown faster TFC decline than patients with lower baseline TFC.
Uniqure had a loss of 0.37 points at 4 years.
The updated Enroll-HD external control shows −0.94 TFC points at 48 months, while the earlier Enroll-HD control produced approximately −1.24 points. Again, I ask here, are these aggressive or conservative control numbers? Where are all the 2 year, 3 year, 4 year studies in hd showing anything like these numbers?
2024 track hd study
pmc.ncbi.nlm.nih.gov/article…
2000 study
Tfc 7-13
0.97 per year
neurology.org/doi/10.1212/WN…
The CREST-E study of creatine for Huntington disease: A randomized controlled trial
N 278
Starting baseline 10.18
Estimated placebo TFC decline was 0.70 points/year; the trial was designed for up to 48 months but was stopped early, with only 36 participants having ≥4 years of primary outcome data.
pubmed.ncbi.nlm.nih.gov/2870…
dash.harvard.edu/server/api/…
2CARE study
609 participants
Starting baseline 10.9
0.83/year
only 34% of participants had completed 5 years of follow-up at the time of study termination, although 91% had completed at least 1 year of follow-up and 69% had completed 3 years
pmc.ncbi.nlm.nih.gov/article…
@peter_mantas @Tim_Corr @laurencurehd @Christina4HD @JRenz0418 @DesertDweller93
Jordan Alexander retweeted
H.C. Wainwright keeps a Buy rating and $185 PT on $NKTR after the Co. presented AA data at #EADV2026 and hosted a conference call to review the data.
$QTTB $NBI
H.C. Wainwright said in its note: Of the eight patients who achieved SALT ≤20 after 52 weeks of rezpeg treatment, 75% (6/8) maintained the response at four months and 63% (5/8) at six months off treatment (NRI, with all patients available for assessment), versus an estimated 30% and 20% for low-dose baricitinib (2 mg) after the same 52 weeks of treatment (cross-trial comparison, Exhibit 1).
Response was also independent of current episode duration, a key prognostic factor in AA: among patients who entered the 16-week treatment extension, 29% with a current episode of <4 years and 30% with an episode of 24 years achieved SALT ≤20 at Week 52, whereas baricitinib 2 mg response fell from an estimated 28% to 11% across the same cut (Exhibit 2).
Most notably, responses kept deepening without drug.
During the six-month off-treatment period, 41% of the 27 patients in the 52-week treatment cohort achieved a deeper best response than on treatment and another 22% maintained their regrowth (Exhibit 3), while SALT ≤10 rose from 7% at Week 52 to 19% (Exhibit 4) and one patient reached SALT 0.
Despite these results, NKTR shares fell 22.4% to $46.99 on October 1, versus a 2.1% decline in the Nasdaq Biotechnology Index (NBI).
We view the move as unjustified and believe the stock is oversold.
We maintain our Buy rating on NKTR and a 12-month price target of $185 per share.
Canaccord Genuity🏁 $NKTR Buy-$153 and said in its initiation report that the Ph3 program for lead asset rezpegaldesleukin in atopic dermatitis has commenced and a Ph3 program in alopecia areata is expected following an end-of-Phase 2 meeting with the FDA—expects rezpeg's unique mechanism of action to appeal to patients and physicians alike, if approved.
Rezpeg has two big advantages in the dermatology space, namely its potential for disease modification and safety.
For anyone freaking out over $NKTR ISRs, this wasn’t new & was the same data previously disclosed. Nearly all reactions were mild to moderate, typically resolved within days & none led to discontinuation. It’s a tolerability issue, but one that was generally well tolerated & potential for < frequent dosing could help further. Very different from the systemic safety concerns & boxed warnings associated with AA JAK inhibitors.
Jordan Alexander retweeted
Long-dated yields appear to be •very• over-extended technically and if they peak and decline, it will be a big catalyst for a rally in growth stocks.
How can $NKTR AtD be worth just $1B EV, which is what remains after today’s $440m market cap stock dump? Didn’t seem like there was much value if any for AA, but guessing there was $440m and it’s now viewed as being worth $0. This surely isn’t a healthy market.
Jordan Alexander retweeted
$qure $clpt
Uniqure management today at Guggenheim
MRI was included in bla
The 3 have not been added to the bla unless the FDA asks for it.
FDA has not made any requests or stipulations at this time regarding the 4 year data.
Confirm trial would be the same as phase 1/2 with inclusion.
The agency likes tfc
1 patient had extremely wild swings on tms, tfc start at 13, right now tfc is still 13. Possible rater has been different 4 times. Tfc hasn’t moved. Not sure why this patient has wild swings.
Tms can have wild swings.
If they excluded the noisy patient on tms, 57 percent cUHDRS
You cannot play that game
Doesn’t believe the 4 year data changes anything regarding the bla. Believes the regulators will see the same thing.
Became aware of the 4 year database issue around late June. They were a bit surprised how chudrs didn’t move in year 3 to 4.
Chdi is working with them to figure out the missingness issue. Possible was Covid issue,
Enroll hd is definitely bias, it underestimates, it works against them which is good. Walid says it definitely underestimates.
They feel low dose is a good control group.
Regarding 5 year data, looking for ways to compare going forward.
Too early to comment on label.
It’s not a durability issue regarding insurance.
Would use HDSA for referrals to procedure sites.
Barrow has 12 neurosurgeons and 12 mri sites, some have 1 to 1. Some sites say they can do 2 a week, some say 1 a month.
For patients, even 1 year saved is important to them. Patients think how many more moments can I maintain in my life. Patients will climb up to get treatment. Across the board, patients are enthusiastic, they understand the missingness. They have real life examples on why people stop showing up. This isn’t numbers to them, this is real life to them.
2 1/2 to 4 million would be expected price, in gene therapy range.
@laurencurehd @Christina4HD
Jordan Alexander retweeted
Okay, so $QURE just got crushed nearly 40%, and a lot of people are reading that as the Huntington’s gene therapy falling apart at year four. I don’t think that’s what’s going on.
What’s actually wild here is the comparison group. By year four, about half of those patients were gone from the data, and the ones who left were getting sicker faster. Leave them out and the remaining controls look healthier, so the drug looks weaker even when the treated patients themselves have not suddenly fallen apart.
That pattern shows up all over medicine, and most people never see it. When a trial cannot ethically leave patients untreated for years, companies often borrow a “control” from a big natural-history database: people with the same disease, matched on paper, who were simply followed over time. It is a clever workaround. It is also fragile. The people who stay in those databases long enough to be counted at year four are not a random sample of the disease. The ones who get worse faster drop out, move to hospice, miss visits, or die. What remains is a quieter, healthier-looking average. Compare a real treated group to that thinned-out average and you can manufacture a “fade” that is partly just the control getting easier to beat.
Huntington’s makes this especially sharp. As most of you know, it comes from one broken gene. That gene builds a sticky huntingtin protein that slowly wrecks the brain, and we still have nothing approved that puts the brakes on that decline. AMT-130, now named ifezuntirgene inilparvovec, tries something blunt and beautiful: one surgery, one dose into the striatum, the deep brain region this disease hits early, and a tiny designed RNA that tells cells to make less huntingtin.
The high-dose group here is tiny, so every number needs humility. At three years, now with 15 people, the main disease score (thinking, movement, and day-to-day function rolled together) got about 80% less worse than matched people watched in that natural-history database. That three-year cut is what the company put in its filing with @FDA. At four years, 12 of those patients were still on that same score, and the slowing fell to 44%. It missed the usual statistical bar (p=0.144). The score that asks a simpler question, can you still work, manage a house, take care of yourself, still looked better: about 61% less decline (nominal p=0.008). That everyday-function score is also what the bigger confirmatory trial will lead with.
And look at what happened underneath those percentages. By month 48, 53% of the matched comparison patients had missing follow-up. The ones who vanished were declining faster than the ones who stayed. If the sickest untreated people leave the spreadsheet, the remaining “no-drug” group looks healthier than real Huntington’s usually does. The gap between drug and no-drug then shrinks on paper. When the company ran the same four-year patients against an older version of that control set, the slowing on the main score came back near 54%. Same treated people. Different ghost of a control. Different story.
To me the sell-off looks like traders bracing for a messier approval path, not like the biology flipped overnight. Twelve patients cannot settle how long a benefit lasts. What this episode can settle is a harder habit: before you trust a year-four “fade,” ask who is still left in the untreated column.
What I am sure is that I truly hate all brain diseases. Disease in general is bad, yes. But brain diseases deserve our special hatred. We should unite as humanity to beat all brain diseases as quickly as possible. That I know...
Jordan Alexander retweeted
“53% of enroll HD control group dropped out due to disease progression at 48 months” #QURE is comparing its clinical patients against the healthiest of who remain in the control pool. Those who left the control group did not leave voluntarily.
Jordan Alexander retweeted
Warning, long tweet:
My head hurts. After today's update, I feel like @uniQure_NV $QURE management has been attempting to fit a square peg into a round hole all along with their comparison to a faulty natural history dataset. This is not totally their fault because with a single arm study, it was the only thing they had to compare the data to.
That said, I fault management in their messaging over the years about the datasets. Why didn't they explain to us in the past that these data are not truly comparable to the patients in our study as a result of the sicker patients dropping out of follow up in Enroll HD? They made it sound as if Enroll HD was the gold standard to compare our data, without ever informing us that there were significant issues with the data caused by the dropout rate as time goes by.
Today's data update proves to me that AMT130 works and is durable. While the messaging about the magnitude of actual efficacy is unclear due to lack of accurate comparator, it is working, I don't see how anyone can deny that. How can they have ever compared our patient data to an ever-increasing faulty database without better disclosure?
Here is a possible comparator, it is speculation; take the 1-year changes which includes the largest number of patients and multiply that change by the number of years to compare. Page 15 of today's presentation shows us what the 1-year decline is for the least amount of people who dropped out for cUHDRS. That came in at a decline of .91 in year 1. While HD patients don't decline in a straight line, it would probably be better than using as the denominator a figure we know to be flawed due to dropouts of the sickest of patients.
Using the above as the comparator, it would mean at 3-years, there would be a decline in NH of 2.73 compared to the number we used last year of 1.52. I question whether or not the 1.52 was accurate based on today's increased understanding. If we instead used 2.73 for the denominator of decline in cUHDRS compared to the decline from baseline in the 15 patients of .28 would have resulted in an almost halt of disease at the 3-year mark. I don't think a decline of 2.73 reflects accurately how the disease progresses, I bet the decline is actually higher than that.
Taking it a step further, our data during year 4 from baseline with the 12 patients went from a decline of .38 to a decline of .90 at month 48, a decline of .52 for just year 4. This is still a slower rate of decline than what the NH showed in year 1 of .91. My guess is in NH in year 4 declines much faster than the year 1 decline of .91. Either way, treated patients only declined by .52 points in year 4 compared to a first year decline of .91 in NH.
NFL data are not subject to bias in any way. It is a lab test and when you compare the data at year 4 of a cumulative increase of 4% to progression in healthy patients of 1-2%/year, the NFL of these HD patients is equal to what you would expect in a healthy population in year 4. I can't explain how data at year 3 reflected an 8-point decline compared to now a 4-point increase but on a cumulative basis, this was an incredible result. Look at slide from last year's presentation below.
Now on to TFC: What we know about TFC is that our data has not changed meaningfully since year 1. There was an initial decline from baseline at year 1 then it has basically been flat. That is the graph we need to look at, don't compare it to a faulty database. This means there is stability beginning 1 year after treatment in the thing that matters most, the patient's ability to live their lives working, driving a car, shopping and generally taking care of themselves without help. See adjusted snippet below for how it basically hasn't changed from year 1.
NFL data are not subject to bias in any way. It is a lab test and when you compare the data at year 4 of a cumulative increase of 4% to progression in healthy patients of 1-2%/year, the NFL of these HD patients is equal to what you would expect in a healthy population in year 4. I can't explain how data at year 3 reflected an 8 point decline compared to now a 4-point increase but on a cumulative basis, this was an incredible result. Look at slide from last year's presentation below.
Over time, the understanding of the data will become more evident that AMT130 is the only treatment to ever show this type of effect on the progression of this disease. It will be an education process that management should have engaged in during the past couple of years but that is water under the bridge. It is now time for them to get moving on this and educate all stakeholders about the true game changer that AMT130 is from HD community to investors to gov't officials to payers. The fact they screwed up by not educating everyone sooner will make the rollout a little more challenging, but they can rectify the situation.
This will be a blockbuster gene therapy, it may just take a little longer for that to materialize, but it will happen. Today was unbelievably disappointing from many aspects but after further review of the data, I am very pleased with the actual slowing of progression for the HD community. More time will continue to demonstrate how effective it truly is.
Jordan Alexander retweeted
Extraordinarily unlikely this is even kind of over for $QURE.
The 3-year data with 15 patients instead of the original 12 now shows an 80% slowing with cUHDRS instead of the original 75%.
The TFC (primary endpoint of the confirmatory trial) was highly statistically significant at 48 months (p=0.008).
53% (!!) of the external control arm had dropped out at the 4 year mark. This of course heavily biases towards enriching the control arm with the slowest progressing patients, and yet there was still a 44% slowing on cUHDRS at a p=0.144, we’ll see where it goes when the cohort expands from 12 to 15 as it just did for the updated 36 month data.
Frankly, I missed a risk with the headline numbers on this readout. I had just assumed that the original Enroll-HD natural history cohort was exclusively comprised of patients that had 4 years of follow-up and so the NH comparator arm at 4 years would be the same as at 3 years.
Never even thought to double check if that was true. However, in retrospect, the 4 year data when they started the study was not the intention so plausibly $qure could have included patients that dropped out after 3 years, and WHOA what a drop out rate.
NfL is 4% above baseline 4 years later, against a background annual increase of ~10% or more.
By almost any metric the benefits seen here far exceed the benefits attributable to donanemab and lecanemab in AD, for a disease that occurs far earlier in life, and for which the target mHTT is actually a primary driver of the disease (the beta-amyloid hypothesis is bogus).
I would be completely shocked if this doesn’t get approved, especially under the new FDA, and if you think most HD specialists won’t see this as strong data and a huge advance relative to where we sat a little over a year ago, well….
The goal here was never a cure. It was substantial disease modifying effect. In my view, AMT-130 has that effect and Dr. Tabrizi is right that this is a huge step forward.
At 0.40 second mark, @MartinShkreli “curious if $QURE keeps going. The reason I bought it is this news should not affect the regulatory review and the stock was at $40 waiting for the regulatory review. Anytime, as anyone who’s been watching knows, when you’re waiting for regulatory review, it’s a very sensitive time for the drug company…so I understand investors are nervous, but wonder if this thing keeps rallying? Maybe I’ll buy it on a pullback or something. Maybe I should just long it and jump back in”
Right or wrong calls isn’t as important as the analysis and he has some of the best “institutional quality” analysis that he shares for free.
9/29/26 -17% since 7/1 xitter.cf/i/broadcasts/1NxaroOWY…
Jordan Alexander retweeted
The *far* more damaging bear case for what *COULD* have happened to $QURE today would have been that the new patients added at the 3 year timepoint eroded the cUHDRS effect and caused it to miss stat sig. That would have been tough to wiggle out of, because, again - the 3 year cUHDRS delta is the accelerated approval endpoint.
But, that effect actually *deepened* with the new patients added at 3 years today.
The 4 year cUHDRS delta of ~50% is still obviously a delta that Huntington's patients would care about and seek out. This delta isn't stat sig because the external control arm ended up being *HALF* the size at year 4 vs year 3.
This is a reasonable explanation, and the messiness of external control is why there is going to be a confirmatory study here...which again, uses TFC, which was still clearly stat sig even at 4 years.
Explaining away loss of statistical significance on the 3 year timepoint with new patients versus the external control with the 2x larger sample size would have been MUCH harder for $QURE to do. That might have thrown a legitimate wrench in the approval plans. Again, fortunately for $QURE, the effect at this timepoint actually *deepened* today.
Market selling this off into the low teens was completely missing the endpoints/timepoints that actually matter here 🤷♂️
Jordan Alexander retweeted
So, uhh.... $QURE is still getting approved, isn't it?
👉The 4 year data from today isn't even part of the accelerated approval data package that was submitted to the FDA. Accelerated approval submission was on 3 year data.
👉The 3 year data with newly added patients got *even better* on cUHDRS delta.
👉The accelerated approval endpoint is cUHDRS at 3 years, but the confirmatory trial endpoint will be TFC. The new 4 year data that people are freaking out about today missed stat sig on cUHDRS, but *is still stat sig on TFC*, which again, will be the actual confirmatory trial endpoint.
👉"There is no placebo group" people always ignore the low dose cohort too. Why? Patients were blinded to dose cohort, making the low dose cohort essentially a placebo cohort with a 10x lower dose. The high dose is *still stat sig superior to the low dose group* at 48 months on both endpoints versus this "pseudo placebo" group.
👉CSF NfL is totally flat after 4 years, whereas it should be up *significantly* in untreated HD patients.
All of the above points will be discussed at the ADCOMM, which was already expected before today's data. The FDA refusing to approve this would sincerely surprise me.
"But what about commercial viability?!" Do you even know what we are talking about here? This is Huntington's disease...You think nobody is going to want the drug because "The 4 year ~50% reduction of disease slightly missed statistical significance against the external control!"
Patients will see ~50% slowing on cUHDRS (missed stat sig) and ~60% slowing on TFC (strongly stat sig) and want the drug. This part is not complicated.
The only question was and is: Approval or no approval?
You think the current FDA is gonna reject this? LOL, ok - let's see.
Jordan Alexander retweeted
from heidi overton's opening remarks in her confirmation hearing: "President Trump's direction for me in this role should I be confirmed is to go fast. Slow and prohibitive requirements for cutting-edge therapies at the FDA means investment is increasingly flowing to China, who has found ways to do things faster and cheaper... China has surpassed the United States as a top venue for clinical trials... When we lose this advantage, we lose our health security. And when we lose our health security, we lose everything." "The FDA has begun work... to make sure every aspect of clinical trials and drug development is optimized." "The recent rapid approval of a new treatment for pancreatic cancer... should be the norm for the FDA."
Looks like Dr Tabrizi’s comments on $QURE AMT-130 are being taken out of context. What would an AMT-130 slowing 40-50% at year 4 from 75% slowing at year 3 look like:
The 3-year analysis compared the 12 high-dose patients with propensity-matched Enroll-HD controls: cUHDRS was −0.38 for AMT-130 versus −1.52 for controls, or 75% slowing.
If the control decline is around −2.0 at year 4, roughly:
75% slowing → AMT-130 −0.50
50% → −1.00
40% → −1.20
So getting down to 40–50% would require AMT-130 to deteriorate from −0.38 at year 3 to roughly −1.0 to −1.2 at year 4. That means more deterioration in year 4 alone than occurred during the first three years combined.
That’s why I don’t read Tabrizi mentioning 40–50% as necessarily hinting that the data are heading there. It sounds more like she’s saying that even 40–50% slowing would still be a major clinical effect.
Sung’s 85–90% comment points the other way: if patients remain relatively stable while the natural-history controls continue declining, the calculated slowing could increase substantially at year 4. And Sung is treating more patients, by far, than Tabrizi. Also, the trend was widening in AMT-130’s favor from year 2 to 3.
Having listened to this a number of times, my sense is Dr. Tabrizi’s reference to an effect size of 40-50% refers to the effect size in the broader HD community if $QURE’s AMT-130 becomes available for treatment.
I do not believe she is referring to the effect size she expects to be seen in the 4 year data for the 12 patients that is upcoming.
This view is partially informed by her and Dr. Wild’s prior commentary (e.g. “beyond our wildest dreams” wrt efficacy), by the fact that it would probably be unwise to answer that question with data pending as a KOL, and by the fact that it not only would be require a substantial change in the trajectory of decline for the 12 patients as they moved from year 3 to year 4, but that change would have to be concentrated in a subset of the patients and correspondingly entail an even larger change in trajectory if we accept the anecdotes of efficacy from Sung, etc.
I think it’s also clear based on her commentary she believes the treatment is effective as she states as really the foundational comment of the interview:
“It tells us what to do. It tells us where we need to target”.
The only way AMT-130 tells us that is if it is actually having a disease modifying effect. Otherwise, it’s useless.
The existence of a disease modifying effect for AMT-130 is the basis on which the drug would be assessed for approval, and a 40-50% “true” effect in the broader HD population would demonstrably yield a blockbuster drug.
Jordan Alexander retweeted
$NKTR
Lots of funky action in this name the past few days, some specific to the ongoing court case and some from bio as a whole. Let's unpack it.
The jury note, paraphrased as "Is there a difference between breach + $1 and no breach + $0?", spooked the market and sent the stock down sharply. Two sides to this.
First, the note is informative, but only a little. It tells us at least one juror sees the $0/$1 outcome as part of their possible resolution space. Where I think the market (or at least fintwit) got it wrong is treating the note as the voice of the entire jury. It could reflect the whole panel, or it could be a single juror's question. It doesn't even tell us direction: it could come from a juror looking for a way to find breach despite doubting the damages case. The price action implied the whole jury is now choosing between $0 and $1, which I think is a big overread.
Second, this is NKTR: a retail/fintwit-heavy, relatively illiquid SMID-cap biotech that moves 5% on a random Tuesday with no news. A 10% move on this headline looks extreme, but near-term price action here mostly reflects value-agnostic traders playing local news and liquidity flow, not a considered repricing of long-term value.
The bigger picture: the case is largely a distraction from the real value, which is Rezpeg. I'm not a biotech expert, but the sell side and most biotech specialists I respect see it as a likely viable commercial product that's underpriced here. If anything, the case matters mainly as an overhang. An uncertain $0-to-$1B+ claim is hard for any acquirer or partner to price, so resolution in almost any direction clears the path for corporate action.
The distraction is creating the opportunity.
Disclosure: Creek Drive and its affiliated funds holds a long position in NKTR. Views expressed are current opinions for information only, subject to change and are not investment advice or a recommendation to buy or sell any security. Investing involves the risk of loss and past performance is not indicative of future performance. See the disclosures link in my bio for more important information.