Biotech 25 years. Capitalist always. Socialism is Cancer. Kicked off X for not liking Socialism. I guess I will stick to Biotech. Live n Learn. Now just Lurking
NJ,PA, FL
Joined December 2025
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UpnDownisBack retweeted
It's been months that I keep saying Hitler was far left. Every time, thousands of clowns show up in my replies to give me history lessons.
So I made a video to answer all these low IQ takes at once.
Topic closed. Next.
UpnDownisBack retweeted
🚨 SOCIALISM IS HERE: The NYC Council just voted to put nonprofits at the FRONT of the line when you sell your own building.
The vote was 38 to 9.
When an owner of a covered building decides to sell, city-certified nonprofits get 20 days to say they're interested and 70 more to make an offer.
That's 90 days of the government picking who gets first shot at YOUR property.
Even after that, the nonprofit can come back and MATCH any outside offer you get.
About 2,100 buildings are covered, and Mayor Zohran Mamdani has pledged to sign it.
None of this should surprise anyone. Back in 2021, Mamdani called for the "full de-commodification" of housing.
He told you exactly what he believed. Now he's doing it.
You bought it. You paid for it. You carry the costs.
But in Mamdani's New York, City Hall decides who gets to buy it.
That's not housing policy. That's SOCIALISM.
UpnDownisBack retweeted
$KYTX: MSToronto 2026 Conf.
Wednesday at 4:30 PM: Full 1-year results from KYSA-8 registrational trial in SPS.
Friday at 11:05 AM: Updated Phase 1 investigator-initiated Multiple Sclerosis highlighting clinical activity and a well-tolerated safety profile in progressive.
UpnDownisBack retweeted
$EYPT Because DME has such a massive inflammatory component, standard anti-VEGF treatments often underperform, leaving the door wide open for Duravyu's intracellular mechanism to outperform standard of care.
UpnDownisBack retweeted
Things are definitely changing in pancreatic cancer! According to $VSTM FDA agreed (for the first time probably) to use ORR and PFS as 1ry endpoints rather than overall survival.
Here is also a list of PDAC catalysts from TDCowen. It is dominated by RAS but there are also some orthogonal mechanisms that could be combined with RAS inhibitors.
To me $ANL's RAS-based ADC at the bottom is the most intriguing one. Probably a direct threat to pan-RAS inhibitors but could still be combined with mutation specific molecules.
UpnDownisBack retweeted
$VSTM $xbi
something VERY interesting in this morning’s conference call…
sorry for the vague post — will see if I can find some time to follow up with more thoughts later
$VSTM
VS-7375 Demonstrates Robust Anti-Tumor Activity Across Advanced KRAS G12D-Mutant Cancers, Highlighted by:
> 50% Confirmed ORR in 2L Pancreatic Ductal Adenocarcinoma and Two Complete Responses in 2L+ Disease (One Confirmed)
> VS-7375 900 mg QD monotherapy achieved a 41% confirmed ORR in the broader 2L+ pancreatic ductal adenocarcinoma (PDAC) patient population and a
> 36% confirmed ORR in 3-4L;
> responses are durable with a majority of patients ongoing >6 months and a 67% landmark 6-month PFS rate
> FDA alignment reached on Phase 3 trial design in 1L mPDAC; plan to open trial by year-end
> Early results in heavily pretreated 3L+ colorectal cancer (CRC) include 33% unconfirmed ORR with 900 mg QD in combination anti-EGFR therapy with no patients with target lesion increases
> VS-7375 achieved 43% confirmed ORR with 600 mg QD monotherapy in 2L+ non-small cell lung cancer (NSCLC) including patients with prior taxane treatment; durable responses were observed and PFS is trending favorably; 900 mg QD dosing ongoing in Phase 2 TARGET-D 202 trial
> With longer follow-up and expanded enrollment VS-7375 900 mg QD maintained a consistent tolerability profile with no evidence of cumulative toxicity and a 2% discontinuation rate due to adverse events, supporting 900 mg QD as the go-forward monotherapy dose and its combination potential
UpnDownisBack retweeted
Small n for sure. But 4 scans (~6m) and ongoing treatment is pretty big deal in CRC
$VSTM
UpnDownisBack retweeted
$VSTM impressive responses in examples below
They still however report 27% vomit like the case with $RVMD daraxonrasib.. and and Zoldonrasib … but mostly grade 1
Liver enzyme elevation is 8-10%. Single digit elevation also seen with daraxonrasib and Zoldonrasib..
so combination with PD1 could be problematic to all of them from liver enzymes. Although RVMD reported some early combo data
Ultimately duration of response what will matters. And that will clear next few months.
$ERAS and $TNGX didn’t report ALT elevation .. but we need to see pubs …
This is why people prematurely get excited about pre clinical reporting like PRMT5 inh from $IDYA but u don’t know what surprising toxicity will emerge ( QT .. ALT ..)
VSTM data look good. It’s based on Gen Fleet improvement of Mirati molecule. Looks like Chinese chemists again doing good job.
UpnDownisBack retweeted
This is partial list. Probably most critical data are from a number if pan K RAS SR2 Inhs in phase 1. Particularly RR in PDAC and comparison to $RVMD and $ERAS pan RAS glues. These data are more critical than G12 D Inhs as they are mutation agonistic .. ERAS team seems more excited about oo15 vs 4001 molecule
We need to hear an update form $AZN compound licensed from China and on $LLY early trials ? Surprising no update for a while from AZN while ERAS update almost q quarter
ERAS update on 0015 in Nov is important after RVMD 24% RR .. that should cast light on pan RAS glues competitive position vs G12D inh.
What matters more is response duration as so far most of these pts relapse rather quickly. This is why durability of response is critical from RVMD & $TNGX combination .. but this is only portion of pts.
Things are definitely changing in pancreatic cancer! According to $VSTM FDA agreed (for the first time probably) to use ORR and PFS as 1ry endpoints rather than overall survival.
Here is also a list of PDAC catalysts from TDCowen. It is dominated by RAS but there are also some orthogonal mechanisms that could be combined with RAS inhibitors.
To me $ANL's RAS-based ADC at the bottom is the most intriguing one. Probably a direct threat to pan-RAS inhibitors but could still be combined with mutation specific molecules.
UpnDownisBack retweeted
another way to look at past 2mos from goldman. biotech degrossing highest since '21.
$SMMT so we are 1 month out from a PUDFA 11/14/26 I am long .... I think we see an approval and a stock price of $28.
UpnDownisBack retweeted
A year ago, I wrote about uniQure's ($QURE) 3 year readout of AMT-130, their gene therapy for Huntington's disease (HD), and said we should wait for the longer follow up. Today, the company released data on another timepoint, the 4 year readout, which now reinforces my earlier argument for the need for further follow up to know if the treatment is really working.
At 4 years, the primary end point, cUHDRS, showed 44% slowing of disease progression in the high dose group (n=12) compared to external controls, down from 75% at 3 years. It was not statistically significant this time (p=0.144), compared to p=0.003 at 3 years. The secondary end point, total functional capacity (TFC), held up better, with 61% slowing (p=0.008), about the same as the 60% at 3 years (p=0.033).
Some context: after the 3 year readout, FDA first said the data was not enough, then in June this year said it was enough, and the company filed for accelerated approval based on the 3 year data. Today's results were not part of that filing, but they change the lens through which one would look at the 3 year data.
The company's explanation for the weaker 4 year result is dropout in the external controls. 53% of the matched controls had no data at 4 years, and those who stayed longer in the study were slower decliners compared to the dropouts. Fair argument. But for that argument to hold, the dropouts one needs to look at are the ones who left the study between year 3 and year 4. According to the company's own slides, the controls with data went from 690 at 3 years to 625 at 4 years, which is a loss of only about 65 people (~9%). So, whatever bias the dropouts caused was already present in the year 3 comparison, which showed 80% slowing in the updated analysis.
Ignoring the controls and looking at the treated patients only, the high dose patients (n=12) had lost 0.38 cUHDRS points at 3 years, and another 0.52 by year 4. That looks like disease progression picking up pace.
In the adjusted numbers, TFC stayed flat between year 3 and 4. But TFC is a coarse scale (0 to 13) that barely moves in early HD, which is why cUHDRS was chosen as the primary end point in the first place. Also, TFC is part of cUHDRS, which points to continuing decline in motor and cognition.
One argument in the treatment's favor is the comparison between the high dose and low dose groups. At 4 years, the high dose group declined by 0.91 on cUHDRS and the low dose group by 1.94, which is about 53% slowing. The low dose group declined similarly to untreated controls from the older ENROLL-HD dataset (also 1.94), so it behaves like a natural control that went through the same surgery and trial visits (though the two doses were not randomized against each other). The between dose difference is similar to the high dose vs control (older control) difference.
CSF NfL, a marker of neuronal damage, went from 11% below baseline at 2 years to 4% above baseline at 4 years. NfL is noisy over short periods, so I wouldn't read too much into it, either in favor of or against the treatment.
So, different ways of looking at the data all land around ~50% slowing at 4 years, not the 75-80% seen at 3 years. It's difficult to say whether the 4 year data indicates regression to the mean in a small group, the treatment effect wearing off, or the patients just entering the fast phase of the disease.
The 5 year data, likely around this time next year, will be the one to watch.
uniqure.com/investors-media/…
Today, UniQure ( $QURE ) announced the 3 yr readout findings of their gene therapy trial for Huntington's disease (HD). At the bottom line, the company reports a statistically significant reduction of disease progression (~75%) compared to an external, propensity matched controls.
Apparently, everyone is excited about the results, as can be seen from the >250% increase in $QURE stock price today. Understandably, a first positive trial news in a long time for a devastating disease with no cure has excited the scientific community and increased the hopes of patients.
I am seeing headlines like "Huntington's disease successfully treated for the first time" and claims like scientists' have found a cure for HD. I am not sure if the findings are that groundbreaking to warrant such claims.
It might be the case that treatment really is working, but I am not sure if the current findings are strong enough to be too confident on the treatment effect. There are many uncertainties around the results. Below are my some of my thoughts.
HD is caused by a triplet repeat mutation HTT gene that somatically expand over time and cause neurodegeneration. The repeat mutation in HTT gene gets translated to polyglutamine repeats in the HTT protein, which is believed to be neurotoxic (though we don't know exactly what's killing the neurons).
Past treatments have largely focussed on knocking down HTT gene using different approaches, none of which translated to clinical benefits. Most notable among them, is tominersen (developed by Roche and Ionis Pharmaceutials), an antisense oligonucleotides (ASO) drug that lowered the production of HTT protein in the brain (both the mutant and normal copies). Although, tominersen successfully reduced the HTT levels in the brain, it failed to treat HD.
All past failed efforts on treating HD by reducing HTT production, led to many critical questions, such as
- Is it safe to blindly knockdown HTT in the brain, as normal versions of the protein might play some important functions ?
- How early one should intervene to make clinically meaningful impact on disease progression? Even though the clinical symptoms appear late in the disease course, the neuronal damage itself seem to start very early in the disease course.
- At what level does the toxicity originates, protein or RNA or DNA? how much of the existing neuronal damage is reversible?
There are many more unanswered questions. Recently, the therapeutic focus have shifted to reducing the somatic expansion of HTT mutation rather than reducing the HTT expression (refer to this article for more details on this, nature.com/articles/d41586-0…).
With this background, here we have a new gene therapy--AMT-130--developed by UniQure that is trying to treat HD by reducing HTT production using a viral vector based genetic drug surgically injected directly into the brain striatum (key brain region affected in HD). The idea is to permanently reprogram the neurons to produce microRNAs that reduce production of HTT proteins (both mutant and normal copies).
It's challenging to have true controls for such trials, so scientists used external controls (in large numbers, n>100) that matched closely to the trial participants with regard to clinical characteristics. There were two groups. One (n=9) received the high dose injection and the other, low dose (n=12)
The primary end point is a composite score called composite unified Huntington's disease rating scale (cUHDRS) calculated from multiple clinical scores measuring motor, cognitive and other functioning capacities of the patients. Additionally, neurofilament light chain, a CSF biomarker of neuronal death, is also measured.
At 24 months follow up (July 2024), the press release reported a statistically significant reduction (~80%) in the cUHDRS decline in high dose group (n=12) vs external controls. But there was no significant effect in the low dose group (n=12). With regard to CSF Nfl, the report showed a slight decrease in trial participants (n=21) compared to baseline, both high and low dose pooled together the CSF. No data on this from individual groups.
Now (Sep 2025), at 36 months follow up, the press release reports a statistically significant reduction (~75%) in the cUHDRS decline in high dose group (n=12) vs external controls. But there is no significant effect in the low dose group (n=12).
With regard to CSF Nfl, the report shows average reduction in CSF Nfl in both low and high dose groups individually compared to baseline. No mention of P values. From the data, the reductions are likely not statistically significant from either baseline or between the high dose and low dose groups.
Reviewing the data, I see two major concerns: small case sample size (paired with unusually large controls) and short follow up period for a noisy outcome measure such as cUHDRS.
Firstly, there are only 12 individuals in each case arm (with 36 months data) and 568 individuals in control arm. The control sample is disproportionately larger than case sample size. It's difficult to confidently assess a different between these two groups. The variations in the control group would be smaller due to large N, but the variations in the case group would be bigger with mere chance pushing the average to extremely higher or lower levels.
Currently, individual data points are not reported. It's possible that even one or two patients with extreme scores would have pushed the average of trial participants higher favoring a statistical significance. If the number of controls is reduced to, let's say, n<100, it's possible the P value becomes bigger, even to non-significant level (P>0.05).
One might get excited about the large effect size, 80%, but effect estimates are meaningless for extremely small sample size.
Secondly, the 3 year follow up is short for tracking HD's disease course. HD has a really long latent period and the disease progression happens slowly until very late stages when things escalate quickly. Also, the neuronal damage happens asynchronously. The disease course can differ wildly between patients with some staying stable for many years while other worsening quickly. Given this complexity, interpreting a 3 year readout based on n=12 individuals is challenging.
My other major concern is the low dose group, in which there is no meaningful effects either at 24 months or at 36 months. Even worse, with regard to some measures they seem perform poorly compared to controls. This is worrying, as it suggests there is no dose dependent effect. But we don't know for sure. Much longer follow up is needed. Adding to the concern, the press release avoided mentioning anything about low dose group, and focussed only on high dose group.
Of course, even a remote possibility that this gene therapy works and may give back years of quality life to HD patients should excite anyone in the field. I am excited too. But at the same time, one should be also cautious in interpreting the results and raising hopes for patients and families.
For now, I'd say we should be cautiously optimistic about this readout and wait for longer follow up results. Of course, it's possible the drug clear regulatory approval and gets rolled out to many patients. But it's gonna take a long time before we really know if it's truly working.
uniqure.com/investors-media/…
I like the chart and the upcoming data on $NKTX in Nov. 6th thru the 11th ...I think they got something cooking here.
UpnDownisBack retweeted
An important read on how we keep America from becoming France, from a Frenchman.
My post about France went viral. Thousands of likes. Many Americans told me: "Democrats aren't socialists. America will never be France." I want to answer that seriously, step by step.
Start with a simple observation. Look at what has gotten cheaper in America over the last 25 years: TVs, phones, software, clothes, toys. Now look at what has exploded: college tuition, healthcare, childcare, housing.
What separates the two lists? The first lives in competitive markets. The second is exactly where government is most involved: subsidies, mandates, licensing, zoning, regulation.
College. Washington lends students almost unlimited money. Universities know the money will always come, so they raise tuition and hire more administrators. The student pays the bill for twenty years. More government money, higher prices.
Housing. Why can't a nurse buy a home in the city where she works? Not because of capitalism. Because of zoning laws, permits, environmental reviews, years of procedure to build a single building. The most expensive places to live in America are the places where it's hardest to build. When building is nearly illegal, prices explode.
Healthcare. The patient almost never sees the price. A third party pays, regulations limit who can compete, and costs climb year after year with no one able to say no.
So here is the trap. The problems you suffer from are not the failure of free markets. They are the places where the market has already been replaced by the state. And the solution you're being offered is more of the same.
That's the Trojan horse. It always works the same way. A real problem. A generous-sounding promise. A program that makes things worse. Then the failure of that program becomes the argument for the next one. People who lived under communism in Poland learned to recognize the lie and the mask the lie wears. The lie never presents itself as a lie. It presents itself as compassion.
In France we are at the end of that road. Debt we can never repay. Young people who can't afford a home. Our best people leaving. And every few years our cities burn. Nobody voted for this. They voted for one more generous promise, fifty years in a row.
If you're a Republican, share this with the Democrat in your life. Not to win an argument. To start a conversation.
If you're a Democrat, I'm not asking you to switch teams. I'm asking you to look at the pattern. Wherever the state took over, life became unaffordable. Don't fix the failures of government with more government.
Stay American. Ask for less state, not more.
UpnDownisBack retweeted
Looking back at our first table, I think we could have done a much better job. We probably rushed it a little, to be fair. And honestly, I wish someone here had pointed that out before we noticed it ourselves. If you ever see something we could improve, please tell us. That’s part of what makes sharing research worthwhile.
The first table wasn’t wrong, but we realized we could get so much more out of the data. So we went back to work, and this new version gives investors a much broader perspective, comparing adjusted equity values with eligible peak sales.
And we’re not finished. $BBIO is still missing, and there are more improvements to make. If you saved or reposted the original table, please replace it with this one. It’s simply much better.
We’re also working on a short Substack article, going company by company, explaining the numbers, assumptions and limitations. Nothing too complicated, just some proper research into a group of really interesting biotech companies.
$INSM $PRAX $CELC $COGT $CYTK $ABVX $RVMD $MDGL $MLYS $VERA $MIRM $SRRK $BBIO
