The dazzling 36-month clinical data announced by uniQure (NASDAQ: QURE) showing a significant slowing of Huntington’s disease (HD) progression in patients treated with its gene therapy candidate AMT-130 was just one of several reasons why the company’s stock more than tripled this past week on the better-than-expected news, reaching a five-year high.
Part of the hyper surge of buying from investors reflected the strikingly positive tone taken by investigators—and analysts—in discussing the results. Key among those results was the statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) in patients treated with the high dose of 6×10^13 gc/subject, meeting the primary endpoint of the study.
“[A] 75% slowing of disease progression is greater than what we even anticipated, expected, and hoped for. That means for one year of disease progression, they will have four years longer in terms of disease-free life,” Sarah Tabrizi, MD, PhD, director of the University College London (UCL) Huntington’s Disease Centre, told analysts Wednesday on a conference call convened by uniQure to discuss the data. “The effect of 75% slowing is a huge effect size and will have massive effects for patients’ lives.”
Other data that drove dizzying growth for uniQure stock also came from topline 36-month efficacy results for high-dose patients in the Phase I/II study, which consisted of trials in the United States (NCT04120493) and in Europe (NCT05243017):
- A statistically significant 60% slowing of disease progression as measured by TFC, which met a key secondary endpoint of the study
- Slowing of disease progression ranging from 59% as measured by Total Motor Score (TMS), to 88% as measured by Symbol Digit Modalities Test (SDMT), to 113% as measured by Stroop Word Reading Test (SWRT).
“These game-changing data really offer a beacon of hope for patients and their families and represent a significant step toward delivering a licensed disease-modifying therapy for Huntington’s disease,” added Tabrizi, who is also a professor of clinical neurology and joint head of the department of neurodegenerative disease at UCL. “I feel we, as a community, must work together to help get this therapy to as many Huntington’s disease patients as possible.”
uniQure plans to submit a Biologics License Application (BLA) to the FDA in the first quarter of 2026, with anticipated U.S. launch later that year. Analysts generally echoed Tabrizi’s optimism about the data and the prospects of AMT-130 to gain approval and reach the market.
“Can support an approval”
“We think these data are definitive and can support an approval with minimal need for regulatory flexibility from the FDA (and therefore with limited regulatory risk), which has been a concern for investors,” commented Joseph P. Schwartz, senior managing director, rare diseases, and a senior research analyst with Leerink Partners, in a research note.
Schwartz raised Leerink’s 12-month price target on uniQure shares 42% from $48 to $68, based in part on the data plus comments on the analyst call from Kylie O’Keefe, uniQure’s chief customer and strategy officer since June, that the company is “looking at pricing AMT-130 in line with other gene therapies.”
That would mean a net price of $1.7 million in the United States and $1 million in the European Union, Schwartz estimated, up from his earlier estimates of $1 million and $800,000, respectively.
O’Keefe also offered an admittedly early estimate of the potential initial total addressable market that is expected to be treated with AMT-130: About 6,000 patients, representing the initially treatable ~30% of the total ~20,000 total diagnosed and symptomatic HD patients in the United States today. Approximately 40,000 U.S. patients are symptomatic for HD.
The Leerink analyst also cited two actions by uniQure to capitalize on the momentum from its strong HD data. One was a $175 million nondilutive senior secured term loan facility with Hercules Capital. The loan facility consists of a refinanced $50 million debt, extending it from January 2027 to October 2030, and an additional $125 million in non-dilutive funding.
The other action cited by Schwartz was uniQure’s commencement of an upsized $300 million public offering of ordinary shares, priced at $47.50 per share, and, for specified investors, pre-funded warrants to purchase 526,316 ordinary shares at the public offering price. Underwriters have a 30-day option to buy up to 947,368 additional ordinary shares at the public offering price, less underwriting discounts and commissions.
Proceeds from the public offering are intended to fund a potential commercial readiness activity—including a commercial launch of AMT-130 and related commercialization activities—plus development of other clinical product candidates, business development initiatives, research projects, and general corporate purposes, according to a preliminary prospectus. Leerink Partners is among the bookrunning managers for the proposed offering, along with Stifel, Guggenheim Securities, and Van Lanschot Kempen. H.C. Wainwright & Co. is acting as lead manager.
Hyperdrive reality, blockbuster forecasts
“We would not be surprised to see the stock trade up 100% or more on today’s news,” Schwartz predicted.
That forecast proved rather conservative.
uniQure stock went on hyperdrive Wednesday, catapulting 248% from $13.66 to $47.50—then rose another 11% to $52.65 Thursday, after reaching $54.55 a minute after the start of trading. Shares climbed an additional 3% Friday, finishing last week at $54.31.
As dramatic as the price surge was the rush of investors drawn to buy uniQure shares. After ranging from 540,100 to over 2.33 million in the month before the big surge, trading volume on Wednesday leaped to nearly 70.1 million shares, and stayed in eight figures Thursday, even while falling to 17.2 million shares.
Another factor in the investor mega-surge is the consensus among analysts that AMT-130 is likely to become a blockbuster (sales of at least $1 billion) gene therapy for uniQure.
Sami Corwin, PhD, a biotechnology-focused healthcare analyst with William Blair, projected in a research note that AMT-130 would generate peak worldwide annual sales of $4 billion by 2032.
“AMT-130 is now positioned to potentially become the first approved therapy to treat the underlying cause of HD,” Corwin wrote. “Overall, these data, combined with the Hercules financing, materially de-risk the BLA pathway, enhance commercial and reimbursement prospects, and represent the most significant positive catalyst for the stock this year.”
Corwin’s forecast is at the high end of projections. Goldman Sachs analyst Salveen Richter has projected $2.5 billion in peak sales for AMT-130 with a 90% success probability. While maintaining her firm’s rating of “Neutral” on uniQure shares, Richter more than quadrupled her firm’s price target on uniQure shares, from $13 to $56.
Other analysts raising their price targets on news of the HD data include:
- Guggenheim Securities (Debjit Chattopadhyay, PhD)—Up by more than triple (239%), from $28 to $95, maintaining a “Buy” rating.
- RBC Capital Markets (Lucas Issi, PhD)—More than double (129%), from $24 to $55, maintaining an “Outperform” rating.
- Chardan Capital (Daniil Gataulin, PhD)—Up by more than double (117%), from $35 to $76, maintaining a “Buy” rating.
- Stifel (Paul Matteis)—Up by more than double (117%), from $30 to $65, maintaining a “Buy” rating.
- Wells Fargo (Yanan Zhu, PhD)—Up by more than double (117%), from $30 to $65, maintaining an “Overweight” rating.
- Mizuho (Uy Ear)—Up by double, from $30 to $60, maintaining an “Outperform” rating.
- Cantor Fitzgerald (Kristen Kluska)—Up 70% from $47 to $80, maintaining an “Overweight” rating.
Coattail effects
uniQure’s surge generated coattail effects that started with a nearly 59% jump from $12.16 to $19.28 for ClearPoint Neuro (NASDAQ: CLPT), which developed and sold to uniQure the device it used in order to precisely surgically implant AMT-130 into the brain. That device, SmartFlow® Neuro Cannula, is an FDA-approved [510(k) clearance] device designed to deliver biologic therapies directly to regions of interest in the brain, bypassing the blood-brain barrier.
ClearPoint would generate as much as $20.3 million in revenue if AMT-130 were to be approved, if even 25% of the 6,000-patient potential treatment population, based on a per-infusion cost of $13,500, according to a research note by B. Riley Securities analyst Anderson Schock, as reported by MarketWatch.
Maury Raycroft, PhD, equity analyst with Jefferies, commented in a research note that uniQure’s solid data for AMT-130 would likely also have positive impacts on three other gene therapy programs in clinical phases:
- ALN-HTT02, a CNS-based silent RNA (siRNA) candidate that uses an exon-1-targeting approach to lower huntingtin (HTT) for HD, being developed by Alnylam Pharmaceuticals (NASDAQ: ALNY) and Regeneron Pharmaceuticals (NASDAQ: REGN). ALN-HTT02 is in a 54-patient Phase Ib single-ascending-dose trial (NCT06585449) in adults with HD, with data expected to be read out next year. Raycroft opined that ALN-HTT02 “could gain wider [market] adoption vs QURE’s neurosurgically administered gene tx.”
- TSHA-102, a self-complementary intrathecally delivered AAV9 gene transfer one-time therapy candidate to treat Rett syndrome, being developed by Taysha Gene Therapies (NASDAQ: TSHA). TSHA-102 is set to start patient enrollment in the pivotal Phase I/II REVEAL trials in the fourth quarter, with topline data set to be announced by the end of 2026. REVEAL consists of one study in girls ages 5–8, NCT06152237; the other in adult females, NCT05606614. Rett is a similarly sized patient market to HD, Raycroft observed.
- SGT-212, an AAV-based gene therapy candidate for the treatment of Friedreich’s ataxia, being developed by Solid Biosciences (NASDAQ: SLDB). Solid said it expects to launch a Phase Ib trial of SGT-212 in the fourth quarter. SGT-212 is designed to deliver full-length human frataxin via a dual route of administration: intradentate nucleus infusion via an FDA-approved, stereotactic, precision MRI-guided device, followed by an intravenous infusion to increase therapeutic FXN levels in the cerebellar dentate nuclei and in the cardiomyocytes, respectively.
Low end forecast
Raycroft hews to the low end of sales forecasts for AMT-130, by citing a consensus of analysts that has projected $1.7 billion in peak sales.
Schwartz of Leerink did not offer a peak sales forecast in his research notes but did project rapidly rising sales for AMT-130 starting in the third quarter of 2026 at $24.1 million, then multiplying to $96.4 million in Q4—$120.5 million next year total—followed by $120.5 million in the first quarter of 2027, then $272.6 million the following quarter ($393.1 million in H1 2027).
The last time uniQure cracked the $50-a-share level was November 30, 2020, when it closed at $50.09 after presenting positive topline Phase III data for etranacogene dezaparvovec, the adeno-associated virus five (AAV5)-based hemophilia B gene therapy now marketed as Hemgenix® by the CSL Behring subsidiary of CSL (ASX: CSL).
uniQure shares have come a long way from their all-time low of $3.78 on July 8, 2024. However, uniQure’s current surge remains far from the company’s all-time high stock price of $82.19 reached on June 21, 2019, on the announcement of upcoming data presentations for that year’s International Society on Thrombosis and Haemostasis (ISTH), held the following month in Melbourne, Australia.
At ISTH 2020, uniQure presented up to nine months of safety and Factor IX activity in a Phase IIb dose-confirmation study of etranacogene dezaparvovec, then known as AMT-061, plus long-term safety and durability data from a Phase I/II trial of a predecessor version of the gene therapy, AMT-060.
Leaders and laggards
- Crinetics Pharmaceuticals (NASDAQ: CRNX) shares jumped 28% from $35.89 to $45.91 on Friday after the company announced FDA approval of its drug Palsonify™ (paltusotine) as a first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Palsonify is a nonpeptide SST2 agonist and the first once daily, oral treatment for adults with acromegaly to gain agency authorization. The FDA based its approval on data from the pivotal Phase III PATHFNDR-1 (NCT04837040) and PATHFNDR-2 (NCT05192382) trials, which assessed Palsonify’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, Palsonify consistently showed rapid onset, reliable biochemical control, and sustained efficacy. Palsonify is expected to be available in the United States in early October.
- Evaxion (NASDAQ: EVAX) shares ballooned 37% Thursday after the company announced that it licensed its preclinical vaccine candidate EVX-B3 to Merck & Co. (NYSE: MRK) as called for under an option and license agreement signed by the companies in September 2024. Merck agreed to pay Evaxion $7.5 million cash and up to $592 million in payments tied to achieving development, regulatory, and sales milestones, plus royalties on net sales. Merck agreed to assume full responsibility and carry all costs for the further development of the EVX-B3 vaccine. EVX-B3, identified with Evaxion’s AI-Immunology™ platform, targets an undisclosed “pathogen associated with repeated infections, increasing incidence, and often serious medical complications, and for which no vaccines are currently available.” The cash payment will extend Evaxion’s cash runway to the first half of 2027.
- PepGen (NASDAQ: PEPG) shares more than doubled, zooming 121% from $2.66 to $5.88 Thursday, following the company’s announcement on Wednesday after the close of trading that a single 15 mg/kg dose of PGN-EDODM1 showed a mean splicing correction of 53.7% in the Phase I FREEDOM-DM1 single ascending dose (SAD) study (NCT06204809). All six patients showed an improvement in splicing. PepGen said the figure was substantially higher than any previously reported splicing correction in patients with myotonic dystrophy type 1 (DM1). PepGen is now conducting the Phase I FREEDOM2-DM1 multiple ascending dose study (NCT06667453), with results from the first cohort of 5 mg/kg anticipated to be released in the first quarter of 2026.
