A potential multi-bagger - Uniqure (QURE US)

As usual. Do you own research. Not financial advice.

Uniqure is a company capable of changing the world so to speak (especially for folks with Huntington disease).

Despite the excitement surrounding gene therapy a few years ago, frankly, not much came of it. My view is Uniqure may well be the torch which can showcase the potential of gene therapy.

2025/2026 was a roller coaster ride for Uniqure. In Sept 25, Uniqure announced result from its trial: " Pivotal study met primary endpoint; high-dose AMT-130 demonstrated statistically significant 75% disease slowing at 36 months as measured by cUHDRS compared to a propensity score-matched external control."

The stock surged from $13-15 to as high as $70. Then it all came crashing down and Uniqure dropped to as low as $9.

Why ? It was previously operating under the guidance of FDA that it could file for accelerated approval following the data release. BUT the FDA under Trump, reneged on the guidance and insisted on Uniqure having to run another randomized clinical trial (which would push back drug approval by a few years).

Luckily for Uniqure, under pressure from the Huntington community in USA and other pharmas (because the new FDA walked back on its guidance for several other drug makers as well), the new FDA chief (Makary) and his appointees (especially Prasad) were replaced.

The "refreshed" FDA informed Uniqure it is now prepared to accept BLA/new drug application for its Huntington gene therapy in Q3, without asking for a full blown phase 3 trial.

Stock has since bounced back to over $45 from the teens..... Its MV is now around $3bn, with minimal sales.

The million dollar question is what to do with the stock here ?

First, we need to understand what is Huntington disease. This is the definition from Google AI: " Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder that causes nerve cells in the brain to gradually break down. Caused by a genetic mutation, it leads to progressive motor, cognitive, and psychiatric symptoms—most notably chorea (uncontrollable, dance-like movements). Symptoms typically emerge in middle age, with no cure available."

I think it is probably fair to call it a curse. If one of the parent has the "bad" Huntington gene, 50% chance that the disease will be passed on. Mostly, the Huntington disease will "manifest" only in middle age (say 30-50). Once symptomatic, life expectancy will be only 10-20 years. Patients will gradually lose cognitive power and motor control. Huntington is a "death" sentence. There is NO medicine / treatment that can stem back the tide for patients.

With this backdrop, we can weigh the potential "impact" of AMT-130, the gene therapy from Uniqure. In its "pivotal" trial, its treatment was found to have slowed down the progress of the Huntington disease by 75% over 3 years. Remember the disease will get worse and worse over 10+ years. By slowing down the pace of deterioration by 3/4, AMT-130 can give back years of normal life to the patient.

This is an anecdote from Dr Sung who was involved in the trial: " The patients Sung treated, all in the early stages of Huntington disease, have now been followed for more than 4 years. “All of my patients who were working full-time are still working full-time,” he said. “Generally, everyone is stable. That is not what we expect to see over this length of time in untreated Huntington disease.” In short, AMT-130 can be life changing (in a good way) for these patients.

What are the bets we are making ? The first part of the bet has 2 legs to it. First, Uniqure will need to file its BLA/new drug application in Q3. Second, Uniqure will release its 4-year follow up data in Q3/Q4 2026. I am prepared to take on this part of the bet i.e. filing will be on time in Q3 (and clock will be ticking for when the gene therapy will be approved) + 4-year data should show its benefits will hold if not further improve. Frankly, this is reflected in the run up in stock price already.

The next part of the bet is the interesting one..... What is the peak sales of AMT-130 ? Various analysts expect peak sales to be around $2-3bn. Typical analysts' model assumes 1000-2000 patients get treated each year in USA. And then ASP of $1-2M per patient. My bet is this is too low. There are 41K patients with symptomatic Huntington in USA and another 200000 patients with the Huntington gene (so 50% of them will have the disease at some point).

The key is AMT-130 works better with the patients who are still early in the progress of the disease..... Thus the TAM is almost everyone one in the 100K pool + some of the 41K patients who are symptomatic. Another X-factor worth track is number of Huntington diagnosis or genetic check up/confirmation. Remember to date, there is no treatment available.... Not surprisingly, some folks actually choose not to test to confirm if they have the "bad" Huntington genes. Once AMT-130 is available, it is sensible for more folks to test for the "bad" Huntington gene. Thus, I would speculate annual treatment volume could be much higher than 1-2K patients a year... ASP I suspect would be more than $1M... closer to $2M...

Potentially, AMT-130 could be a $5-10bn blockbuster (5000 patients * $1-2M) in USA alone. Assume Europe will be half the size of US sales.... AMT-130 has the making of the first gene therapy blockbuster.

Of course, this will be a multi-year story. It will take time to build up payor/insurance coverage in USA. Plus training the surgery centres + surgeons. The procedure for AMT-130 is actually quite involved. Patients need to undergo general anesthetic. The operation can take 8-12 hours. The operation requires surgeons to drill through 3 spots in the skull and inject the drug into regions in the brain (3 if memory serves).

Uniqure has the potential to be a very exciting story. Multi-year growth trajectory.... Its TAM is over $100bn (100K patients * $1M). Furthermore, analysts may be "under" in terms of the potential of AMT-130. It is a monopoly i.e. no other treatments available for Huntington patients. And demand will be there.

In addition, Uniqure is working on using gene therapy to help patients with Refractory Mesial Temporal Lobe Epilepsy. The TAM for MTLE is even larger (240K patients). Again, gene therapy has the potential to be life changing for these patients. In its low dose/safety phase 1 trial, 3 out of 6 patients had much lower frequency of epilepsy episodes following administration of the drug (roughly 80% less).

With biotech, there will inevitably be set back. Key risks would be payors pushing back on coverage.... Also there is a small company (Skyhawk) working on oral drug for Huntington (supposedly seeing good data in phase 1).... If it works, it will be very bad for Uniqure... If you can take a pill and slow down the progress of Huntington, then gene therapy may not be worth it. Nevertheless, the Skyhawk trial will take 3-4 years to mature.

In summary, if all goes according to plan, it is not inconceivable to see Uniqure grow to >$10bn MV. If its second drug for MTLE works, the sky is the limit. BUT it is a long road ahead... Plus, there are clearly risks (FDA approval + 4-year data and company needs to execute its commercialization efforts well.

PS... if you have the stock, hang on for the ride. If you are new to the stock, have a small position around $40 and see how it goes.... It is a tough one to bet the farm on given it has run up so hard already. And in this frothy market environment, there will inevitably be pull back along the way.