Denali Therapeutics DNLI reported primary analysis data from an early to mid-stage study of its pipeline candidate, tividenofusp alfa (DNL310), in 47 patients with Hunter syndrome (MPS II) over a 24-week treatment period, along with additional long-term follow-up data. DNLI’s wholly-owned program, tividenofusp alfa, is an Enzyme Transport Vehicle-enabled iduronate-2-sulfatase replacement therapy in development for MPS II.

Per the additional long-term data readout from the phase I/II study, treatment with tividenofusp alfa resulted in significant and substantial reductions in key disease biomarkers within the central nervous system and peripheral system, bringing them to normal or near-normal levels. Such biomarkers included cerebrospinal fluid and urine heparan sulfate, as well as neurofilament light, a recognized marker of neurodegeneration.

Per Denali, such efficacy data suggests the pervasive nature of treatment effects in MPS II patients over the longer term.

Shares of DNLI have plunged 28.1% in the past three months compared with the industry’s decline of 6.6%.

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The therapy led to meaningful clinical outcomes, including normalized liver volume after 24 weeks, continued improvement in hearing thresholds across all tested frequencies, and notable skill gains in most participants in adaptive behavior and cognitive assessments. Moreover, the candidate was generally safe and overall well-tolerated by MPS II patients.

Treatment-related adverse events were mostly mild to moderate in severity. Denali reported that there were three cases of serious adverse events that were manageable with continued treatment. However, one MPS II patient discontinued treatment due to a moderate infusion-related reaction and other non-treatment-related adverse events.

These additional longer-term data will be presented at an upcoming medical conference in San Diego, CA.

Recent Regulatory Updates on DNLI’s MPS II Program

Last month, Denali announced that the FDA has granted Breakthrough Therapy Designation to tividenofusp alfa for the MPS II indication. This designation is intended to expedite the development and review of therapeutic drugs, which are being evaluated for the treatment of serious or life-threatening conditions. Additionally, the candidate also enjoys the FDA’s Fast Track designation in the United States for the same indication. In 2022, the European Medicines Agency granted Priority Medicines designation to tividenofusp alfa for MPS II.

In September 2024, Denali announced the outcome of a successful meeting with the FDA, providing a path to filing a biologics license application (BLA) for tividenofusp alfa for accelerated approval and subsequent conversion to full approval for the treatment of Hunter syndrome.

In the latest press release, the company stated that the additional long-term data, along with the recent Breakthrough Therapy designation, further support the planned BLA submission in early 2025 with an expected U.S. launch in late 2025 or early 2026.

DNLI is also currently enrolling in the phase II/III COMPASS study on tividenofusp alfa in North America, South America and the EU to support global approval of the candidate. The study will enroll patients in two separate cohorts, Cohort A and Cohort B, comprising MPS II patients with and without neuronopathic disease, respectively. The participants are randomized 2:1 to receive either tividenofusp alfa or idursulfase, respectively.

Denali believes that such phenomenal progress in the MPS II program will inform and accelerate additional therapeutics programs in its lysosomal storage disease portfolio, including Sanfilippo syndrome Type A.

Denali Therapeutics Inc. Price and Consensus

Denali Therapeutics Inc. price-consensus-chart | Denali Therapeutics Inc. Quote

DNLI’s Zacks Rank and Stocks to Consider

Denali currently carries a Zacks Rank #3 (Hold).

Some better-ranked stocks from the sector are Castle Biosciences CSTL, BioMarin Pharmaceutical BMRN and Alnylam Pharmaceuticals ALNY. While CSTL sportsa Zacks Rank #1 (Strong Buy), BMRN and ALNY carry a Zacks Rank #2 (Buy) each at present. You can see the complete list of today’s Zacks #1 Rank stocks here.

In the past 30 days, Castle Biosciences’ earnings estimates for 2024 have increased from 34 cents to 45 cents per share. During the same timeframe, the loss per share for 2025 has improved from $1.84 to $1.51. In the past three months, shares of Castle Biosciences have plunged 16.4%.

CSTL’s earnings beat estimates in each of the trailing four quarters, delivering an average surprise of 172.72%.

In the past 30 days, estimates for BioMarin Pharmaceutical’s 2024 earnings per share have remained constant at $3.28. Estimates for 2025 earnings per share have decreased from $4.01 to $4 during the same timeframe. In the past three months, BioMarin Pharmaceutical shares have lost 4.1%.

BMRN’s earnings beat estimates in each of the trailing four quarters, delivering an average surprise of 28.7%.

In the past 30 days, estimates for Alnylam Pharmaceuticals’ 2024 loss per share have remained constant at 39 cents. The estimate for 2025 earnings per share is currently pegged at 41 cents. In the past three months, shares of Alnylam Pharmaceuticals have gained 0.3%.

ALNY’s earnings beat estimates in three of the trailing four quarters and matched once, delivering an average surprise of 65.67%.

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