Marketdash
Back to News

FDA Puts Denali's Pompe Disease Trial on Ice, But Company Says It's Just a Speed Bump

MarketDash Editorial Team
2 days ago
The FDA hit pause on Denali Therapeutics' rare disease trial, asking for protocol tweaks including a lower starting dose and additional safety monitoring. The biotech says no extra studies are needed and expects only minimal delays in getting started.

Sometimes regulatory setbacks are disasters. Sometimes they're just paperwork. Denali Therapeutics Inc. (DNLI) is betting this one falls into the latter category.

The U.S. Food and Drug Administration slapped a clinical hold on Denali's investigational new drug application for DNL952, a Phase 1 candidate being developed for Pompe disease. Before you panic, here's what the FDA actually wants: a protocol amendment with a lower starting dose, some revised inclusion criteria, additional safety monitoring commitments, and stopping rules.

The reason? Preclinical hypersensitivity reactions showed up in GAA mouse models during testing. Now, this sounds concerning until you learn that these reactions are basically par for the course. They're commonly observed across all GAA enzyme replacement therapies in mice, meaning this isn't some unique red flag specific to Denali's drug.

Here's the important part: the FDA didn't ask for additional nonclinical studies. That's usually the time-consuming, expensive request that can derail timelines. Denali has already submitted its response to the agency and expects minimal delays in kicking off the Phase 1 study once the FDA gives feedback.

The company filed with the SEC on Thursday confirming it's still on track to submit a Clinical Trial Application for DNL952 in Europe during the first half of 2026.

Investor Day Brings Pipeline Progress Report

Denali wasn't just dealing with regulatory holds this week. The company held its 2025 Investor Day on Thursday and delivered updates across its development pipeline, with some genuinely interesting momentum building.

The headline act is tividenofusp alfa for MPS II, also known as Hunter Syndrome. The Biologics License Application is currently under FDA review, with a target action date of April 5, 2026, under the Prescription Drug User Fee Act. Denali has wrapped up a Late Cycle Meeting with the FDA and is now deep into labeling discussions. Commercial readiness activities are moving forward, which tells you the company is preparing for an actual launch.

Meanwhile, enrollment in Cohort A (the neuronopathic group) of the Phase 2/3 COMPASS study for tividenofusp alfa is expected to finish by December 2025.

There's also DNL126, being developed for MPS IIIA, or Sanfilippo Syndrome Type A. The Phase 1/2 study remains on schedule for completion in 2026, potentially setting up an accelerated approval pathway and commercial launch by the end of 2027. Denali plans to present initial Phase 1/2 data at the 2026 WORLD Symposium, and Phase 3 planning is already underway.

Royalty Pharma Writes a Big Check

Also on Thursday, Royalty Pharma plc (RPRX) announced a $275 million synthetic royalty funding agreement tied to future net sales of tividenofusp alfa. This is the kind of deal that signals confidence in a drug's commercial potential.

The transaction comes with conditions, naturally. The big one: Denali needs to secure U.S. FDA accelerated approval of tividenofusp alfa for the money to start flowing.

Here's how the payment structure works: Royalty Pharma will hand over an initial $200 million at closing. Then there's an additional $75 million payment contingent on achieving European Medicines Agency approval by December 31, 2029.

In exchange, Royalty Pharma gets a 9.25% royalty on worldwide net sales of tividenofusp alfa. The royalty payments stop once they hit a multiple of 3.0x, or 2.5x if that milestone is reached by the first quarter of 2039. It's a bet on blockbuster potential with a defined exit.

Wall Street Weighs In

BTIG reiterated its Buy rating on Denali Therapeutics and maintained a price target of $32.

Wedbush kept its Outperform rating and bumped up its price forecast from $30 to $31.

DNLI Price Action: Denali Therapeutics shares were down 0.10% at $20.09 at the time of publication on Friday, according to market data.

Back to News

FDA Puts Denali's Pompe Disease Trial on Ice, But Company Says It's Just a Speed Bump

MarketDash Editorial Team
2 days ago
The FDA hit pause on Denali Therapeutics' rare disease trial, asking for protocol tweaks including a lower starting dose and additional safety monitoring. The biotech says no extra studies are needed and expects only minimal delays in getting started.

Sometimes regulatory setbacks are disasters. Sometimes they're just paperwork. Denali Therapeutics Inc. (DNLI) is betting this one falls into the latter category.

The U.S. Food and Drug Administration slapped a clinical hold on Denali's investigational new drug application for DNL952, a Phase 1 candidate being developed for Pompe disease. Before you panic, here's what the FDA actually wants: a protocol amendment with a lower starting dose, some revised inclusion criteria, additional safety monitoring commitments, and stopping rules.

The reason? Preclinical hypersensitivity reactions showed up in GAA mouse models during testing. Now, this sounds concerning until you learn that these reactions are basically par for the course. They're commonly observed across all GAA enzyme replacement therapies in mice, meaning this isn't some unique red flag specific to Denali's drug.

Here's the important part: the FDA didn't ask for additional nonclinical studies. That's usually the time-consuming, expensive request that can derail timelines. Denali has already submitted its response to the agency and expects minimal delays in kicking off the Phase 1 study once the FDA gives feedback.

The company filed with the SEC on Thursday confirming it's still on track to submit a Clinical Trial Application for DNL952 in Europe during the first half of 2026.

Investor Day Brings Pipeline Progress Report

Denali wasn't just dealing with regulatory holds this week. The company held its 2025 Investor Day on Thursday and delivered updates across its development pipeline, with some genuinely interesting momentum building.

The headline act is tividenofusp alfa for MPS II, also known as Hunter Syndrome. The Biologics License Application is currently under FDA review, with a target action date of April 5, 2026, under the Prescription Drug User Fee Act. Denali has wrapped up a Late Cycle Meeting with the FDA and is now deep into labeling discussions. Commercial readiness activities are moving forward, which tells you the company is preparing for an actual launch.

Meanwhile, enrollment in Cohort A (the neuronopathic group) of the Phase 2/3 COMPASS study for tividenofusp alfa is expected to finish by December 2025.

There's also DNL126, being developed for MPS IIIA, or Sanfilippo Syndrome Type A. The Phase 1/2 study remains on schedule for completion in 2026, potentially setting up an accelerated approval pathway and commercial launch by the end of 2027. Denali plans to present initial Phase 1/2 data at the 2026 WORLD Symposium, and Phase 3 planning is already underway.

Royalty Pharma Writes a Big Check

Also on Thursday, Royalty Pharma plc (RPRX) announced a $275 million synthetic royalty funding agreement tied to future net sales of tividenofusp alfa. This is the kind of deal that signals confidence in a drug's commercial potential.

The transaction comes with conditions, naturally. The big one: Denali needs to secure U.S. FDA accelerated approval of tividenofusp alfa for the money to start flowing.

Here's how the payment structure works: Royalty Pharma will hand over an initial $200 million at closing. Then there's an additional $75 million payment contingent on achieving European Medicines Agency approval by December 31, 2029.

In exchange, Royalty Pharma gets a 9.25% royalty on worldwide net sales of tividenofusp alfa. The royalty payments stop once they hit a multiple of 3.0x, or 2.5x if that milestone is reached by the first quarter of 2039. It's a bet on blockbuster potential with a defined exit.

Wall Street Weighs In

BTIG reiterated its Buy rating on Denali Therapeutics and maintained a price target of $32.

Wedbush kept its Outperform rating and bumped up its price forecast from $30 to $31.

DNLI Price Action: Denali Therapeutics shares were down 0.10% at $20.09 at the time of publication on Friday, according to market data.