Key Takeaways DNLI won FDA approval for Avlayah, the first new Hunter syndrome therapy option in nearly 20 years.DNLI discontinued BIIB122 after a mid-stage trial missed primary and secondary goals.Denali continues advancing multiple pipeline programs, with BEACON data expected in the first half of 2027. Denali Therapeutics, Inc. (DNLI - Free Report) is developing innovative therapies for neurodegenerative diseases using its proprietary TransportVehicle platform, which is designed to help medicines cross the blood-brain barrier.
The company is currently developing drugs for neurodegenerative diseases, lysosomal storage disorders and other serious diseases.
It received a significant boost earlier this year with the FDA approval of its lead drug, Avlayah, for the treatment of Hunter syndrome. Avlayah is an enzyme replacement therapy indicated for pediatric patients with Hunter syndrome (MPS II), targeting neurological symptoms when initiated early.
This accelerated approval is particularly noteworthy as it introduces the first new therapeutic option for this rare disorder in nearly two decades.
Denali is also advancing several other pipeline candidates either alone or in collaboration with other partners.
The company’s clinical-stage portfolio includes DNL126 for Sanfilippo syndrome type A (MPS IIIA), DNL593 for GRN-related frontotemporal dementia, DNL952 for Pompe disease and DNL628 for Alzheimer's disease.
Denali is also advancing several early-stage pipeline candidates, including DNL921 for Alzheimer's disease, DNL111 for Parkinson’s and Gaucher diseases, DNL622 for Hurler syndrome (MPS I), and DNL422 (OTV) for Parkinson’s disease.
Denali has also collaborated with other pharma and biotech giants like Sanofi, Biogen (BIIB - Free Report) and Takeda (TAK - Free Report) to develop other candidates.
However, recent pipeline setbacks are concerning. In May 2026, Denali and partner Biogen reported disappointing mid-stage results for BIIB122 (DNL151) in early-stage Parkinson's disease, with the study missing both its primary and secondary endpoints.
Biogen and Denali subsequently discontinued the development of BIIB122 in idiopathic Parkinson’s disease.
Nonetheless, Denali will continue to independently advance the phase IIa BEACON study evaluating the small-molecule inhibitor in patients carrying pathogenic LRRK2 variants.
The global BEACON study is designed to assess safety, pharmacokinetics and biomarkers of lysosomal pathway engagement.
Data from the BEACON study is expected in the first half of 2027. The study is being led by Denali and funded through a Collaboration and Development Funding Agreement with a third party.
Earlier, in April 2026, partner Takeda ended its collaboration on DNL593 for frontotemporal dementia associated with GRN mutations, returning full rights to Denali. While Takeda stated the decision reflected strategic priorities rather than safety or efficacy concerns, the loss of a major pharmaceutical partner reduces external validation and shifts the full development and financial burden to Denali.
Competition for DNLI in Parkinson’s DiseasePharma giant Roche (RHHBY - Free Report) is developing prasinezumab, a potential first-in-class antibody for the treatment of Parkinson’s disease that is designed to target a key epitope within the C-terminus of alpha-synuclein, in partnership with Prothena.
Roche is conducting the phase III PARAISO study in approximately 900 participants with early-stage Parkinson's disease, with the study's primary completion expected in 2029.
Denali’s Price, Valuation and EstimatesShares of the company have surged 37.9% year to date compared with the industry’s growth of 1.1%.
Image Source: Zacks Investment Research
Going by the price/book ratio, DNLI’s shares currently trade at 3.88X, higher than its mean of 3.02X and the industry’s mean of 3.52X.
Image Source: Zacks Investment Research
The Zacks Consensus Estimate for 2026 loss per share is unchanged at $2.77 over the past 60 days, while that for 2027 loss has narrowed to $2.53 from $2.57 in the same time frame.
July 09, 2026 16:01 ET | Source: Denali Therapeutics Inc.
Denali co-founder and CEO Ryan Watts, Ph.D., to deliver opening plenary address at 2026 AAIC in London on July 12, 2026
Presentation will highlight recent scientific advances and future opportunities to accelerate discovery and development of medicines for neurodegenerative diseases
Denali is advancing multiple investigational therapies designed to cross blood-brain barrier for Alzheimer’s disease, including DNL628 (OTV:MAPT) targeting tau and DNL921 (ATV:Abeta) targeting amyloid beta
SOUTH SAN FRANCISCO, Calif., July 09, 2026 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today announced that co-founder and Chief Executive Officer Ryan Watts, Ph.D., will deliver the opening plenary address, titled “Accelerating the Discovery and Development of Medicines for Neurodegeneration,” at the Alzheimer’s Association International Conference® (AAIC), taking place July 12-15 in London. Dr. Watts will discuss recent scientific advances and future opportunities including new insights in the biology of disease, the use of biomarkers for diagnosis and assessment of treatment effect, and the potential for therapeutics to cross the blood-brain barrier for enhanced delivery to the brain.
“We are entering a new era of drug development for Alzheimer’s disease, driven by significant developments in biology, biomarkers and the blood-brain barrier, which has been a major hurdle for the treatment of neurodegenerative disease,” said Dr. Watts. “At Denali, our work has focused on solving the challenge of brain delivery so that people living with neurologic diseases such as Alzheimer’s can benefit from the power of biotherapeutics. We are excited to be part of the community working to transform the lives of millions of individuals and families worldwide by applying these scientific breakthroughs to deliver the next generation of therapies for Alzheimer’s disease.”
Denali Therapeutics has developed and clinically validated the TransportVehicle™, a proprietary technology designed to effectively deliver biologic therapeutics such as antibodies, enzymes and oligonucleotides across the blood-brain barrier by leveraging the body’s natural iron transport system (the transferrin receptor). In March 2026, Denali received accelerated approval from the U.S. Food and Drug Administration for the first and only FDA-approved biologic specifically designed to cross the blood-brain barrier: AVLAYAH™ (tividenofusp alfa-eknm), an enzyme replacement therapy for the treatment of neurologic manifestations of Hunter syndrome (mucopolysaccharidosis type II) when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment.
Denali is developing a broad portfolio of investigational, TransportVehicle-enabled therapeutic candidates including DNL628 (OTV:MAPT) and DNL921 (ATV:Abeta) targeting tau and amyloid beta, respectively, the two hallmark pathologies of Alzheimer’s disease.
DNL628 (OTV:MAPT) is enabled by the Oligonucleotide TransportVehicle™ (OTV) and is designed to target the MAPT gene that encodes for tau, which has been shown to be closely associated with cognitive decline. Preclinical research (link) demonstrated that the OTV achieved broad and uniform central nervous system distribution of antisense oligonucleotides, including deeper brain structures, following intravenous administration as compared to intrathecally delivered therapy.1 The first patients in Denali’s Phase 1b clinical study of DNL628 were dosed in the first half of 2026, and Denali expects clinical safety and biomarker proof-of-concept data from the study in 2027.
DNL921 (ATV:Abeta) is enabled by the Antibody TransportVehicle™ (ATV) and is designed to reduce amyloid plaques. In preclinical research published in the journal Science (link), Denali demonstrated improved brain distribution of ATV:Abeta and reduced risk of swelling and small bleeds in the brain – effects collectively known as amyloid-related imaging abnormalities (ARIA) – compared to conventional antibody treatment. The findings suggest that TransportVehicle-enabled brain delivery of immunotherapy bypasses amyloid-laden large vessels by traveling through smaller capillaries, offering a potential strategy to mitigate ARIA risk seen with first-generation anti-amyloid therapies.2 Denali submitted a Clinical Trial Application (CTA) for DNL921 in the first half of 2026 and, pending regulatory approval of the CTA, expects to initiate a Phase 1/1b clinical trial, with potential for clinical safety and biomarker proof-of-concept data in 2027.
About the Denali TransportVehicle™ Platform
The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes and oligonucleotides throughout the whole body, including the brain, by crossing the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, which are expressed at the BBB and deliver the TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the TV platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates. The TV platform has been clinically validated, with AVLAYAH™ (tividenofusp alfa-eknm) as the first FDA-approved medicine leveraging transferrin receptor to cross the BBB.
About Denali Therapeutics
Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier (BBB) using its proprietary TransportVehicle™ platform. With the first FDA-approved biologic specifically designed to cross the BBB, a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform life for people with neurodegenerative diseases, lysosomal storage disorders and other serious diseases. For more information, please visit www.denalitherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements by Denali’s Chief Executive Officer; statements regarding expectations for Denali’s TransportVehicle™ (TV) platform and its therapeutic and commercial potential; including the potential to deliver enzymes and the Enzyme TransportVehicle™ (ETV) franchise, antibodies and the Antibody TransportVehicle™ (ATV) franchise, and oligonucleotides and the Oligonucleotide TransportVehicle™ (OTV) franchise; statements regarding plans, timelines and expectations related to AVLAYAH™ (tividenofusp alfa-eknm); statements regarding plans, timelines and expectations related to the DNL628 clinical development program, including the ongoing Phase 1 study and timing of data readouts; and statements regarding plans, timelines and expectations related to the DNL921 clinical development program, including the planned Phase 1 study, the potential to mitigate amyloid-related imaging abnormalities (ARIA) and the timing of data readouts. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to, uncertainties related to the FDA’s policies and accelerated approval program; risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a commercial company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; whether the current ongoing trials have been powered sufficiently to demonstrate approvability to regulatory agencies; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; the uncertainty surrounding regulatory approvals required for commercialization in the U.S., Europe or other international jurisdictions; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; the implementation and success of Denali’s strategic plans for its business, product candidates and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 26, 2026 and May 7, 2026, respectively, and Denali’s future reports to be filed with the SEC. Except for AVLAYAH, Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.
References
Barker SJ, Thayer MB, Kim S, et al. Targeting the transferrin receptor to transport anti-sense oligonucleotides across the mammalian blood-brain barrier. Sci Transl Med 2024 Aug 14;16(760).Pizzo ME, Plowey ED, Khoury N, et al. Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA. Science 2025 Aug 7;389(6760).
Investor Contact:
Laura Hansen [email protected]
Key Takeaways Denali gained 59.4% YTD as Avlayah approval marked its shift to a commercial-stage company.DNLI will receive $195 million from selling its Rare Pediatric Disease Priority Review Voucher.DNLI regained full rights to DNL593 after Takeda ended the partnership for strategic reasons. Denali Therapeutics, Inc. (DNLI - Free Report) has put up a stupendous year-to-date performance. Shares of the company have surged 59.4% year to date compared with the industry’s growth of 5.9%. The stock has outperformed the sector and the S&P 500 Index during this time frame.
The rally is largely attributed to investor optimism surrounding FDA approval of its lead drug, Avlayah, for the treatment of Hunter syndrome, as well as other regulatory updates.
DNLI Outperforms Industry, Sector & S&P 500 Index
Image Source: Zacks Investment Research
While the approval serves as a major catalyst, a deeper assessment of the company's growth drivers and potential risks will be essential to determine whether current levels represent an attractive entry point.
Avlayah Approval Positions DNLI for Long-Term UpsideAvlayah is an enzyme replacement therapy indicated for pediatric patients with Hunter syndrome (MPS II), targeting neurological symptoms when initiated early.
Developed by Denali, Avlayah is enabled by its TransportVehicle platform, which facilitates delivery of biologics throughout the body, including the brain.
Approval was based on strong biomarker data, showing a 91% reduction in cerebrospinal fluid heparan sulfate levels, a key disease marker.
This accelerated approval is particularly noteworthy as it introduces the first new therapeutic option for this rare disorder in nearly two decades. The continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory study.
Denali’s ongoing global phase II/III COMPASS study is expected to provide confirmatory data and support regulatory filings for tividenofusp alfa-eknm worldwide, including in young adult patients with Hunter syndrome.
The approval came with a Rare Pediatric Disease Priority Review Voucher (“PRV”).
Last month, DNLI entered into a definitive agreement to sell its PRV, which is expected to generate gross proceeds of $195 million.
The added financial flexibility will help advance Denali’s broad TransportVehicle-enabled clinical portfolio for lysosomal storage disorders and neurodegenerative diseases.
DNLI’s Other Pipeline CandidatesDenali's clinical-stage portfolio includes DNL126 for Sanfilippo syndrome type A (MPS IIIA), DNL593 for GRN-related frontotemporal dementia, DNL952 for Pompe disease and DNL628 for Alzheimer's disease.
Denali is also advancing several early-stage pipeline candidates, including DNL921 for Alzheimer's disease, DNL111 for Parkinson’s and Gaucher diseases, DNL622 for Hurler syndrome (MPS I), and DNL422 (OTV) for Parkinson’s disease.
Denali has also collaborated with other pharma and biotech giants like Sanofi (SNY - Free Report) , Biogen (BIIB - Free Report) and Takeda (TAK - Free Report) to develop other candidates.
In May 2026, Denali and partner Biogen announced disappointing top-line results from a mid-stage study evaluating BIIB122 (DNL151) in individuals with early-stage Parkinson’s disease. The study did not meet its primary or secondary endpoints.
Biogen and Denali have discontinued the development of BIIB122 in idiopathic Parkinson’s disease.
Nonetheless, Denali will continue to independently advance the phase IIa BEACON study evaluating the small-molecule inhibitor in patients carrying pathogenic LRRK2 variants.
Partner Sanofi is developing eclitasertib for moderate-to-severe ulcerative colitis.
In April 2026, Denali announced that partner Takeda decided to terminate their collaboration for DNL593 (PTV:PGRN) in frontotemporal dementia associated with GRN mutations (FTD-GRN).
The termination returns full rights to the program to Denali. According to DNLI, Takeda's decision was driven by strategic priorities rather than any efficacy or safety concerns.
However, Takeda’s exit may raise concerns. Even though the decision was not tied to safety or efficacy, the loss of a large pharma partner removes external validation and shared financial burden.
Denali’s Valuation and EstimatesGoing by the price/book ratio, DNLI’s shares currently trade at 4.51X, higher than its mean of 3.02X for the industry and the industry’s mean of 3.64X.
Image Source: Zacks Investment Research
The Zacks Consensus Estimate for 2026 loss per share has narrowed to $2.77 from $2.90 over the past 60 days, while that for 2027 loss has narrowed to $2.53 from $2.69 in the same time frame.
Image Source: Zacks Investment Research
Invest in DNLI Stock NowThe approval of Avlayah represents Denali’s transition into a commercial-stage company and a potential inflection point in its long-term growth trajectory. As its first marketed product, Avlayah introduces a new revenue stream, though the pace and scale of commercialization will be critical in determining its ultimate financial impact.
Beyond near-term revenues, the approval also validates Denali’s proprietary TransportVehicle platform, which is designed to enable biologic therapies to cross the blood-brain barrier — an area that has historically posed significant challenges.
On the financial front, Denali appears well capitalized, ending the first quarter with approximately $1.05 billion in cash and investments. This provides sufficient runway to support ongoing clinical development and strategic initiatives. Narrowing loss estimates indicate improving investor sentiment and a clearer path toward operational leverage.
The sale of PRV provides a significant non-dilutive capital infusion, strengthening the company’s balance sheet without requiring an equity raise.
We remain bullish on the stock's prospects and believe it offers additional upside potential. Accordingly, we view the shares favorably for prospective investors, while existing shareholders may consider maintaining their positions to capitalize on further growth opportunities.
June 18, 2026 08:00 ET | Source: Denali Therapeutics Inc.
Proceeds from transaction to support advancement of Denali’s broad TransportVehicle™-enabled clinical portfolio for lysosomal storage disorders and neurodegenerative diseasesDenali was awarded Priority Review Voucher following FDA approval of AVLAYAH™, the first FDA-approved biologic specifically designed to cross blood-brain barrier SOUTH SAN FRANCISCO, Calif., June 18, 2026 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today announced it has entered into a definitive agreement to sell its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $195 million. The U.S. Food and Drug Administration (FDA) awarded the PRV to Denali following accelerated approval of the enzyme replacement therapy AVLAYAH™ (tividenofusp alfa-eknm) for the treatment of Hunter syndrome (mucopolysaccharidosis type II; MPS II) in March 2026. AVLAYAH is the first FDA-approved medicine in an emerging class of biotherapeutics designed to cross the blood-brain barrier via transferrin receptor (TfR)-mediated transport.
"The Priority Review Voucher program is an important and effective mechanism to support the development of medicines for rare pediatric diseases. Monetizing this PRV strengthens our financial flexibility at a pivotal moment as we build on the momentum created by the FDA approval of AVLAYAH, the first FDA-approved biotherapeutic designed to reach the whole body, including the brain," said Alexander Schuth, M.D., Chief Operating and Financial Officer of Denali Therapeutics. "The proceeds will fuel the advancement and acceleration of our broad clinical pipeline, including additional Enzyme TransportVehicle programs for lysosomal storage disorders and Oligonucleotide and Antibody TransportVehicle programs targeting Alzheimer's and other neurodegenerative diseases."
Denali's clinical-stage portfolio includes DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA), DNL593 (PTV:PGRN) for GRN-related frontotemporal dementia, DNL952 (ETV:GAA) for Pompe disease and DNL628 (OTV:MAPT) for Alzheimer's disease. Denali also has multiple programs in the Investigational New Drug (IND)-enabling stage, including DNL921 (ATV:Abeta) for Alzheimer's disease, DNL111 (ETV:GCase) for Parkinson's disease and Gaucher disease, DNL622 (ETV:IDUA) for Hurler syndrome (MPS I) and DNL422 (OTV:SNCA) for Parkinson's disease.
The PRV transaction is subject to customary closing conditions, including expiration of the applicable waiting period under the Hart-Scott Rodino Antitrust Improvements Act.
About the Denali TransportVehicle™ Platform
The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes and oligonucleotides throughout the whole body, including the brain, by crossing the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, which are expressed at the BBB and deliver the TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the TV platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates. The TV platform has been clinically validated, with AVLAYAH™ (tividenofusp alfa-eknm) as the first FDA-approved medicine leveraging transferrin receptor to cross the BBB.
About Denali Therapeutics
Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier (BBB) using its proprietary TransportVehicle™ platform. With the first FDA-approved biologic specifically designed to cross the BBB, a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform life for people with neurodegenerative diseases, lysosomal storage disorders and other serious diseases. For more information, please visit www.denalitherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding the timeline and likelihood of satisfying closing conditions for, and consummating the sale of, the Priority Review Voucher (“PRV”); expected use of proceeds from the sale of the PRV and the anticipated impact on Denali's cash runway; plans, timelines and expectations related to Denali's Enzyme TransportVehicle™ (ETV) franchise and its therapeutic and commercial potential; plans, timelines and expectations related to AVLAYAH™ (tividenofusp alfa-eknm); and statements by Denali’s Chief Operating and Financial Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to, uncertainties related to the FDA’s policies and accelerated approval program; risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a commercial company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; whether the current ongoing trials have been powered sufficiently to demonstrate approvability to regulatory agencies; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; the uncertainty surrounding regulatory approvals required for commercialization in the U.S., Europe or other international jurisdictions; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; the implementation and success of Denali’s strategic plans for its business, product candidates and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 26, 2026 and May 7, 2026, respectively, and Denali’s future reports to be filed with the SEC. Except for AVLAYAH, Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.
Key Takeaways DNLI signed a definitive agreement to sell its Rare Pediatric Disease PRV for $195M in gross proceeds.The PRV was awarded after FDA accelerated approval of Avlayah for Hunter syndrome in March 2026.DNLI said the non-dilutive funding will help advance its clinical portfolio in key disease areas. Denali Therapeutics Inc. (DNLI - Free Report) announced that it has entered into a definitive agreement to sell its Rare Pediatric Disease Priority Review Voucher (“PRV”).
The sale will generate gross proceeds of $195 million.
The PRV was granted to DNLI following the FDA accelerated approval of Avlayah (tividenofusp alfa-eknm) in March 2026 for the treatment of Hunter syndrome (mucopolysaccharidosis type II, or MPS II).
The transaction provides a significant non-dilutive capital infusion, strengthening the company’s balance sheet without requiring an equity raise. The added financial flexibility will help advance Denali’s broad TransportVehicle-enabled clinical portfolio for lysosomal storage disorders and neurodegenerative diseases.
The PRV sale remains subject to customary closing conditions, including the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
Shares of DNLI have gained 41.2% year to date against the industry’s 1.7% decline.
Image Source: Zacks Investment Research
More on DNLI’s AvlayahAvlayah is the first FDA-approved therapy based on an emerging of biotherapeutics designed to cross the blood-brain barrier using transferrin receptor (TfR)-mediated transport technology.
The approval for Avlayah has significantly boosted DNLI’s growth prospects.
Denali's clinical-stage portfolio includes DNL126 for Sanfilippo syndrome type A (MPS IIIA), DNL593 for GRN-related frontotemporal dementia, DNL952 for Pompe disease and DNL628 for Alzheimer's disease.
Denali is also advancing several early-stage pipeline candidates, including DNL921 for Alzheimer's disease, DNL111 for Parkinson’s and Gaucher diseases, DNL622 for Hurler syndrome (MPS I), and DNL422 (OTV) for Parkinson’s disease.
Denali has also collaborated with other pharma and biotech giants like Sanofi (SNY - Free Report) , Biogen (BIIB - Free Report) and Takeda (TAK - Free Report) to develop other candidates.
Last month, Denali and partner Biogen announced disappointing top-line results from a mid-stage study evaluating BIIB122 (DNL151) in individuals with early-stage Parkinson’s disease.
The study did not meet its primary or secondary endpoints.
Consequently, Biogen and Denali have discontinued the development of BIIB122 in idiopathic Parkinson’s disease.
Nonetheless, Denali will continue independently advancing the phase IIa BEACON study on evaluating the small molecule inhibitor in patients carrying pathogenic LRRK2 variants.
Partner Sanofi is developing eclitasertib for moderate to severe ulcerative colitis.
In April 2026, Denali announced that partner Takeda decided to terminate their collaboration for DNL593 (PTV:PGRN) in frontotemporal dementia associated with GRN mutations (FTD-GRN).
The termination, effective 60 days after notice, returns full rights to the program to Denali. Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
Information in Investor’s Business Daily is for informational and educational purposes only and should not be construed as an offer, recommendation, solicitation, or rating to buy or sell securities. The information has been obtained from sources we believe to be reliable, but we make no guarantee as to its accuracy, timeliness, or suitability, including with respect to information that appears in closed captioning. Historical investment performances are no indication or guarantee of future success or performance. Authors/presenters may own the stocks they discuss. We make no representations or warranties regarding the advisability of investing in any particular securities or utilizing any specific investment strategies. Information is subject to change without notice. For information on use of our services, please see our Terms of Use.
*Real-time prices by Nasdaq Last Sale. Real-time quote and/or trade prices are not sourced from all markets. Ownership data provided by LSEG and Estimate data provided by FactSet.
IBD, IBD Digital, IBD Live, IBD Weekly, Investor's Business Daily, Leaderboard, MarketDiem, MarketSurge and other marks are trademarks owned by Investor's Business Daily, LLC.
Key Takeaways DNLI won FDA accelerated approval for Avlayah, its first drug for Hunter syndrome in nearly 20 years.Avlayah showed 91% reduction in key biomarker CSF HS, with 93% patients reaching normal levels.DNLI's TransportVehicle platform enables brain delivery, with a confirmatory COMPASS study ongoing. Denali Therapeutics, Inc. (DNLI - Free Report) secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome.
The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder. It is also the first approved therapy in a new class of biologics designed to cross the blood-brain barrier by targeting the transferrin receptor.
The continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
More on DNLI’s First Commercial DrugDeveloped by Denali, Avlayah is enabled by its TransportVehicle platform, which facilitates delivery of biologics throughout the body, including the brain. The approval also comes with a Rare Pediatric Disease Priority Review Voucher.
Hunter syndrome is caused by a deficiency of the iduronate 2-sulfatase enzyme, leading to the buildup of harmful substances in tissues, including the brain, and resulting in progressive cognitive, motor and organ damage.
Avlayah is an enzyme replacement therapy indicated for pediatric patients with Hunter syndrome (MPS II), targeting neurological symptoms when initiated early.
Approval was based on strong biomarker data, showing a 91% reduction in cerebrospinal fluid heparan sulfate levels (CSF HS), a key disease marker.
In a phase I/II study, treatment led to a 91% reduction in CSF HS levels from baseline at 24 weeks (95% CI: 89%–92%). By that time, 93% of patients (41 of 44) achieved CSF HS levels within the normal range.
The ongoing global phase II/III COMPASS study is expected to provide confirmatory data and support regulatory filings worldwide, including in young adult patients with Hunter syndrome.
Positive outcomes from this study could further expand the drug’s commercial potential and reinforce Denali’s position in the rare neurodegenerative disease market.
This milestone represents a major advancement for the Hunter syndrome community, addressing longstanding unmet needs, particularly neurological complications. Avlayah is administered weekly and is expected to become available in the United States shortly, supported by patient access programs from Denali.
What Does This Mean for DNLI?Shares of Denali gained 7.15% on March 25, following the news of FDA approval.
In the past six months, Denali stock has gained 54.8% compared with the industry’s growth of 11.6%.
Image Source: Zacks Investment Research
The approval marks the company’s first commercial product and a potential inflection point for its long-term growth story.
While the successful commercialization holds the key, the approval of Avlayah underscores the potential of Denali’s TransportVehicle platform to address the longstanding challenge of delivering biologic therapies across the blood-brain barrier, with the goal of transforming treatment for a broad range of neurodegenerative diseases, lysosomal storage disorders and other serious conditions affecting millions worldwide.
DNLI’s Deep Pipeline Also Boosts Growth StudyDenali boasts a deep pipeline. One promising asset is DNL126, being developed for Sanfilippo syndrome type A, a rare pediatric neurodegenerative disorder. DNLI is also evaluating DNL628 (OTV:MAPT) for Alzheimer’s disease.
Strategic partnerships further strengthen Denali’s development capabilities and help mitigate financial and clinical risk.
Denali is developing other candidates in partnership with Takeda (TAK - Free Report) , Biogen (BIIB - Free Report) and Sanofi (SNY - Free Report) .
Denali and Takeda have collaborated to develop DNL593, an investigational therapeutic designed to deliver progranulin across the blood-brain barrier for the treatment of granulin (GRN) mutation-associated frontotemporal dementia (FTD-GRN).
Denali and Biogen continue co-development of BIIB122.
Biogen is leading the global phase IIb LUMA study, evaluating BIIB122's impact on disease progression in early-stage PD. Data is expected in mid-2026.
Denali is conducting the phase IIa BEACON study, specifically enrolling participants with LRRK2-associated PD to assess how LRRK2 inhibition may impact this disease.
In October, Denali submitted an investigational new drug application (IND) for DNL952 (ETV:GAA) to begin clinical studies in Pompe disease. Last month, Denali announced that the FDA has lifted the clinical hold on the investigational new drug (IND) application for DNL952. Phase I study start-up activities are underway.
Sanofi is developing eclitasertib for the treatment of moderate-to-severe ulcerative colitis. Data from the phase II study is expected in the first half of the year.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
April 03, 2026 13:30 ET | Source: Denali Therapeutics Inc.
Denali plans to continue clinical development of DNL593, which is designed to deliver progranulin to the brain using TransportVehicle™ technologyResults from ongoing Phase 1/2 study in patients with FTD-GRN expected by the end of 2026 SOUTH SAN FRANCISCO, Calif., April 03, 2026 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today announced that it has received notification from Takeda of its decision to terminate the collaboration agreement between the two companies to co-develop and co-commercialize DNL593 (PTV:PGRN). The decision was driven by strategic considerations and is not related to efficacy or safety data. DNL593 is an investigational progranulin replacement therapy utilizing Denali’s Protein TransportVehicle™ (PTV) to deliver progranulin across the blood-brain barrier to the brain for the treatment of frontotemporal dementia-granulin (FTD-GRN). Denali has led development activities and will regain full control of DNL593 and its intellectual property portfolio.
“While we have greatly valued our partnership, we are pleased to regain full ownership of DNL593. We remain confident in the scientific rationale and the data generated to date, and we look forward to advancing DNL593 independently. We plan to report results from the ongoing Phase 1/2 trial by the end of 2026,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “Our TransportVehicle platform is the first FDA-approved blood-brain barrier-crossing technology, enabling a robust portfolio with broad potential across neurodegenerative diseases like frontotemporal dementia, where there are no currently approved treatment options to slow the progression of this devasting disease.”
As previously disclosed, data from the ongoing Phase 1/2 study of DNL593, including biomarker results, are expected by the end of 2026. Enrollment in this study is completed with a total of 40 participants with FTD-GRN. Interim results from Part A of the Phase 1/2 study in healthy volunteers demonstrated dose-dependent increases in cerebrospinal fluid progranulin levels, consistent with robust brain delivery of DNL593. DNL593 was generally well tolerated, and there have been no significant safety signals to date.
About Frontotemporal Dementia (FTD)
FTD is the most common form of dementia in people under 60 years of age. While the progression of symptoms varies by individual, FTD brings an inevitable decline in function together with changes in personality and social behaviors, and sometimes language and/or motor dysfunction. Mutations in the granulin (GRN) gene, which encodes the progranulin (PGRN) protein, generally result in reduced levels of PGRN and are amongst the most common genetic causes of FTD. There are currently no approved medications to stop or slow the progression of FTD or FTD-GRN.
About the Denali TransportVehicle™ Platform
The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes and oligonucleotides throughout the whole body, including the brain, by crossing the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, which are expressed at the BBB and deliver the TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the TV platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates. The TV platform has been clinically validated and five TV-enabled programs are currently in clinical development.
About Denali Therapeutics
Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier using its proprietary TransportVehicle™ platform. With a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform life for people with neurodegenerative diseases, lysosomal storage disorders and other serious diseases. For more information, please visit www.denalitherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, plans, timelines and expectations related to Denali’s TransportVehicle™ platform, including its potential application across current and future product candidates and its ability to deliver therapeutics to the brain; plans, timelines and expectations related to DNL593, including the timing and availability of data readouts from the ongoing Phase 1/2 study, the significance of interim data from the Phase 1/2 study including with respect to tolerability and safety, and the potential therapeutic benefit of DNL593; and statements by Denali’s Chief Executive Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to, uncertainties related to the FDA’s policies and accelerated approval program; risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a commercial company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; whether the current ongoing trials have been powered sufficiently to demonstrate approvability to regulatory agencies; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; the uncertainty surrounding regulatory approvals required for commercialization in the U.S., Europe or other international jurisdictions; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; the implementation and success of Denali’s strategic plans for its business, product candidates and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 26, 2026, and Denali’s future reports to be filed with the SEC. Except for AVLAYAH™ (tividenofusp alfa-eknm), Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.
Denali Therapeutics Inc. (NASDAQ:DNLI – Get Free Report) has been given a consensus recommendation of “Moderate Buy” by the sixteen ratings firms that are covering the stock, MarketBeat.com reports. One equities research analyst has rated the stock with a sell recommendation, one has given a hold recommendation, twelve have issued a buy recommendation and two have issued a strong buy recommendation on the company. The average twelve-month price target among analysts that have updated their coverage on the stock in the last year is $34.8182.
DNLI has been the topic of several research reports. The Goldman Sachs Group upped their price objective on Denali Therapeutics from $35.00 to $40.00 and gave the stock a “buy” rating in a report on Thursday, March 26th. Weiss Ratings reissued a “sell (d-)” rating on shares of Denali Therapeutics in a research note on Wednesday, January 21st. Stifel Nicolaus boosted their target price on Denali Therapeutics from $34.00 to $41.00 and gave the stock a “buy” rating in a research report on Thursday, March 26th. BTIG Research upped their price target on Denali Therapeutics from $36.00 to $38.00 and gave the company a “buy” rating in a research note on Wednesday, March 25th. Finally, Jefferies Financial Group reiterated a “buy” rating and issued a $40.00 price target on shares of Denali Therapeutics in a report on Monday, March 2nd.
Read Our Latest Report on Denali Therapeutics
Denali Therapeutics Stock Performance DNLI opened at $20.65 on Friday. Denali Therapeutics has a 1-year low of $10.57 and a 1-year high of $23.77. The stock has a market capitalization of $3.27 billion, a PE ratio of -6.95 and a beta of 1.10. The company has a current ratio of 9.16, a quick ratio of 9.16 and a debt-to-equity ratio of 0.01. The firm has a 50-day moving average price of $20.49 and a two-hundred day moving average price of $18.05.
Denali Therapeutics (NASDAQ:DNLI – Get Free Report) last announced its earnings results on Thursday, February 26th. The company reported ($0.73) earnings per share (EPS) for the quarter, topping analysts’ consensus estimates of ($0.75) by $0.02. During the same quarter last year, the business earned ($0.67) EPS. As a group, equities analysts anticipate that Denali Therapeutics will post -2.71 earnings per share for the current fiscal year.
Insider Transactions at Denali Therapeutics In other news, insider Alexander O. Schuth sold 17,218 shares of the firm’s stock in a transaction dated Tuesday, January 6th. The shares were sold at an average price of $16.50, for a total value of $284,097.00. Following the transaction, the insider owned 282,828 shares of the company’s stock, valued at approximately $4,666,662. This trade represents a 5.74% decrease in their position. The sale was disclosed in a document filed with the Securities & Exchange Commission, which is available through this hyperlink. Also, CEO Ryan J. Watts sold 35,198 shares of Denali Therapeutics stock in a transaction that occurred on Tuesday, January 6th. The stock was sold at an average price of $16.50, for a total transaction of $580,767.00. Following the sale, the chief executive officer owned 296,833 shares of the company’s stock, valued at approximately $4,897,744.50. This represents a 10.60% decrease in their position. The SEC filing for this sale provides additional information. Corporate insiders own 12.50% of the company’s stock.
Institutional Trading of Denali Therapeutics A number of institutional investors have recently bought and sold shares of DNLI. Vanguard Group Inc. boosted its position in shares of Denali Therapeutics by 8.9% in the 4th quarter. Vanguard Group Inc. now owns 13,057,890 shares of the company’s stock worth $215,586,000 after purchasing an additional 1,064,972 shares during the last quarter. Baillie Gifford & Co. increased its holdings in Denali Therapeutics by 6.2% in the fourth quarter. Baillie Gifford & Co. now owns 12,310,889 shares of the company’s stock valued at $203,253,000 after purchasing an additional 719,304 shares during the last quarter. T. Rowe Price Investment Management Inc. lifted its stake in Denali Therapeutics by 28.7% in the fourth quarter. T. Rowe Price Investment Management Inc. now owns 7,254,132 shares of the company’s stock valued at $119,766,000 after buying an additional 1,615,565 shares during the period. Temasek Holdings Private Ltd lifted its stake in Denali Therapeutics by 30.9% in the fourth quarter. Temasek Holdings Private Ltd now owns 7,012,974 shares of the company’s stock valued at $115,784,000 after buying an additional 1,657,142 shares during the period. Finally, State Street Corp boosted its holdings in Denali Therapeutics by 14.6% during the fourth quarter. State Street Corp now owns 6,263,371 shares of the company’s stock worth $103,408,000 after buying an additional 799,110 shares during the last quarter. Institutional investors and hedge funds own 92.92% of the company’s stock.
About Denali Therapeutics (Get Free Report)
Denali Therapeutics is a clinical‐stage biopharmaceutical company focused on developing therapies for neurodegenerative diseases. The company’s research leverages a proprietary Blood–Brain Barrier Transport Vehicle (TV) platform designed to enable large molecules, including antibodies and enzymes, to penetrate the central nervous system. Denali’s approach includes small molecules, monoclonal antibodies and gene therapy candidates aimed at key drivers of disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Among Denali’s lead programs is an orally delivered leucine‐rich repeat kinase 2 (LRRK2) inhibitor for Parkinson’s disease, and an anti‐TREM2 antibody designed to modulate microglial activity in Alzheimer’s patients.
See Also Five stocks we like better than Denali Therapeutics
Receive News & Ratings for Denali Therapeutics Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Denali Therapeutics and related companies with MarketBeat.com's FREE daily email newsletter.
« PREVIOUS HEADLINEDENTSPLY SIRONA Inc. (NASDAQ:XRAY) Given Average Recommendation of “Hold” by Analysts
NEXT HEADLINE »Public Storage (NYSE:PSA) Given Consensus Recommendation of “Hold” by Analysts
SG Americas Securities LLC boosted its holdings in Denali Therapeutics Inc. (NASDAQ:DNLI – Free Report) by 291.6% in the fourth quarter, according to its most recent 13F filing with the Securities and Exchange Commission. The institutional investor owned 149,592 shares of the company’s stock after buying an additional 111,391 shares during the period. SG Americas Securities LLC owned approximately 0.10% of Denali Therapeutics worth $2,470,000 as of its most recent filing with the Securities and Exchange Commission.
Other hedge funds and other institutional investors have also bought and sold shares of the company. Headlands Technologies LLC purchased a new stake in shares of Denali Therapeutics during the 2nd quarter valued at $26,000. Johnson Financial Group Inc. purchased a new stake in Denali Therapeutics during the 3rd quarter valued at about $29,000. State of Wyoming bought a new position in Denali Therapeutics during the 2nd quarter worth approximately $29,000. Quarry LP purchased a new position in Denali Therapeutics in the 3rd quarter worth approximately $64,000. Finally, Intrust Bank NA purchased a new position in Denali Therapeutics in the 3rd quarter worth approximately $154,000. Institutional investors own 92.92% of the company’s stock.
Denali Therapeutics Price Performance Shares of NASDAQ:DNLI opened at $20.65 on Friday. The firm has a market capitalization of $3.27 billion, a P/E ratio of -6.95 and a beta of 1.10. The company has a debt-to-equity ratio of 0.01, a quick ratio of 9.16 and a current ratio of 9.16. The stock has a 50 day moving average price of $20.49 and a 200-day moving average price of $18.05. Denali Therapeutics Inc. has a 52-week low of $10.57 and a 52-week high of $23.77.
Denali Therapeutics (NASDAQ:DNLI – Get Free Report) last released its quarterly earnings results on Thursday, February 26th. The company reported ($0.73) earnings per share for the quarter, beating the consensus estimate of ($0.75) by $0.02. During the same period in the prior year, the business earned ($0.67) EPS. As a group, equities research analysts anticipate that Denali Therapeutics Inc. will post -2.71 EPS for the current fiscal year.
Insider Transactions at Denali Therapeutics In other news, CEO Ryan J. Watts sold 35,198 shares of the company’s stock in a transaction dated Tuesday, January 6th. The shares were sold at an average price of $16.50, for a total value of $580,767.00. Following the sale, the chief executive officer directly owned 296,833 shares of the company’s stock, valued at $4,897,744.50. This represents a 10.60% decrease in their position. The transaction was disclosed in a filing with the Securities & Exchange Commission, which is available through the SEC website. Also, insider Alexander O. Schuth sold 17,218 shares of the stock in a transaction dated Tuesday, January 6th. The stock was sold at an average price of $16.50, for a total transaction of $284,097.00. Following the completion of the transaction, the insider owned 282,828 shares of the company’s stock, valued at approximately $4,666,662. The trade was a 5.74% decrease in their ownership of the stock. The SEC filing for this sale provides additional information. 12.50% of the stock is owned by corporate insiders.
Analysts Set New Price Targets Several brokerages have recently issued reports on DNLI. Wedbush cut their target price on shares of Denali Therapeutics from $31.00 to $30.00 and set an “outperform” rating on the stock in a report on Thursday, December 11th. The Goldman Sachs Group raised their price target on shares of Denali Therapeutics from $35.00 to $40.00 and gave the stock a “buy” rating in a report on Thursday, March 26th. Stifel Nicolaus boosted their price objective on shares of Denali Therapeutics from $34.00 to $41.00 and gave the company a “buy” rating in a research report on Thursday, March 26th. HC Wainwright raised their target price on Denali Therapeutics from $32.00 to $42.00 and gave the stock a “buy” rating in a research note on Thursday, March 26th. Finally, UBS Group initiated coverage on Denali Therapeutics in a report on Wednesday, January 7th. They set a “buy” rating on the stock. Two analysts have rated the stock with a Strong Buy rating, twelve have given a Buy rating, one has assigned a Hold rating and one has issued a Sell rating to the company’s stock. Based on data from MarketBeat.com, the company has a consensus rating of “Moderate Buy” and a consensus target price of $34.82.
Get Our Latest Stock Report on DNLI
Denali Therapeutics Company Profile (Free Report)
Denali Therapeutics is a clinical‐stage biopharmaceutical company focused on developing therapies for neurodegenerative diseases. The company’s research leverages a proprietary Blood–Brain Barrier Transport Vehicle (TV) platform designed to enable large molecules, including antibodies and enzymes, to penetrate the central nervous system. Denali’s approach includes small molecules, monoclonal antibodies and gene therapy candidates aimed at key drivers of disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Among Denali’s lead programs is an orally delivered leucine‐rich repeat kinase 2 (LRRK2) inhibitor for Parkinson’s disease, and an anti‐TREM2 antibody designed to modulate microglial activity in Alzheimer’s patients.
Read More Five stocks we like better than Denali Therapeutics Want to see what other hedge funds are holding DNLI? Visit HoldingsChannel.com to get the latest 13F filings and insider trades for Denali Therapeutics Inc. (NASDAQ:DNLI – Free Report).
Receive News & Ratings for Denali Therapeutics Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Denali Therapeutics and related companies with MarketBeat.com's FREE daily email newsletter.
Capricorn Fund Managers Ltd acquired a new stake in Denali Therapeutics Inc. (NASDAQ:DNLI – Free Report) in the fourth quarter, according to the company in its most recent filing with the Securities and Exchange Commission. The institutional investor acquired 62,197 shares of the company’s stock, valued at approximately $1,027,000.
Other institutional investors and hedge funds have also made changes to their positions in the company. Foresite Capital Management VI LLC acquired a new stake in shares of Denali Therapeutics in the third quarter valued at approximately $14,520,000. AlphaQuest LLC boosted its holdings in Denali Therapeutics by 224.1% in the 3rd quarter. AlphaQuest LLC now owns 74,422 shares of the company’s stock valued at $1,081,000 after purchasing an additional 51,458 shares during the last quarter. Aberdeen Group plc grew its stake in shares of Denali Therapeutics by 23.4% in the 3rd quarter. Aberdeen Group plc now owns 1,113,586 shares of the company’s stock valued at $16,169,000 after buying an additional 210,835 shares during the period. Principal Financial Group Inc. increased its holdings in shares of Denali Therapeutics by 18.5% during the 3rd quarter. Principal Financial Group Inc. now owns 1,271,190 shares of the company’s stock worth $18,458,000 after buying an additional 198,207 shares during the last quarter. Finally, Holocene Advisors LP increased its position in shares of Denali Therapeutics by 677.8% during the 3rd quarter. Holocene Advisors LP now owns 3,135,712 shares of the company’s stock worth $45,531,000 after purchasing an additional 2,732,540 shares during the last quarter. 92.92% of the stock is currently owned by institutional investors and hedge funds.
Insiders Place Their Bets In other news, insider Alexander O. Schuth sold 17,218 shares of the business’s stock in a transaction on Tuesday, January 6th. The stock was sold at an average price of $16.50, for a total value of $284,097.00. Following the completion of the transaction, the insider directly owned 282,828 shares of the company’s stock, valued at $4,666,662. The trade was a 5.74% decrease in their ownership of the stock. The transaction was disclosed in a legal filing with the SEC, which is available through the SEC website. Also, CEO Ryan J. Watts sold 35,198 shares of the business’s stock in a transaction that occurred on Tuesday, January 6th. The shares were sold at an average price of $16.50, for a total transaction of $580,767.00. Following the completion of the transaction, the chief executive officer directly owned 296,833 shares of the company’s stock, valued at approximately $4,897,744.50. This represents a 10.60% decrease in their position. The disclosure for this sale is available in the SEC filing. 12.50% of the stock is currently owned by insiders.
Wall Street Analysts Forecast Growth DNLI has been the topic of a number of research analyst reports. BTIG Research boosted their target price on Denali Therapeutics from $36.00 to $38.00 and gave the company a “buy” rating in a research report on Wednesday, March 25th. Robert W. Baird lifted their price objective on Denali Therapeutics from $29.00 to $32.00 and gave the company an “outperform” rating in a research note on Thursday, March 26th. Wedbush dropped their price objective on Denali Therapeutics from $31.00 to $30.00 and set an “outperform” rating on the stock in a report on Thursday, December 11th. Morgan Stanley boosted their target price on Denali Therapeutics from $40.00 to $42.00 and gave the company an “overweight” rating in a report on Thursday, March 26th. Finally, Stifel Nicolaus raised their price target on Denali Therapeutics from $34.00 to $41.00 and gave the stock a “buy” rating in a report on Thursday, March 26th. Two equities research analysts have rated the stock with a Strong Buy rating, twelve have assigned a Buy rating, one has assigned a Hold rating and one has issued a Sell rating to the company’s stock. Based on data from MarketBeat.com, the company has an average rating of “Moderate Buy” and an average price target of $34.82.
Check Out Our Latest Analysis on DNLI
Denali Therapeutics Stock Performance Shares of DNLI stock opened at $20.65 on Monday. The company has a current ratio of 9.16, a quick ratio of 9.16 and a debt-to-equity ratio of 0.01. The stock has a 50 day simple moving average of $20.49 and a 200-day simple moving average of $18.08. The company has a market cap of $3.27 billion, a price-to-earnings ratio of -6.95 and a beta of 1.10. Denali Therapeutics Inc. has a 12-month low of $10.57 and a 12-month high of $23.77.
Denali Therapeutics (NASDAQ:DNLI – Get Free Report) last posted its quarterly earnings results on Thursday, February 26th. The company reported ($0.73) earnings per share for the quarter, beating analysts’ consensus estimates of ($0.75) by $0.02. During the same period in the previous year, the company earned ($0.67) earnings per share. On average, equities analysts forecast that Denali Therapeutics Inc. will post -2.71 EPS for the current year.
Denali Therapeutics Profile (Free Report)
Denali Therapeutics is a clinical‐stage biopharmaceutical company focused on developing therapies for neurodegenerative diseases. The company’s research leverages a proprietary Blood–Brain Barrier Transport Vehicle (TV) platform designed to enable large molecules, including antibodies and enzymes, to penetrate the central nervous system. Denali’s approach includes small molecules, monoclonal antibodies and gene therapy candidates aimed at key drivers of disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Among Denali’s lead programs is an orally delivered leucine‐rich repeat kinase 2 (LRRK2) inhibitor for Parkinson’s disease, and an anti‐TREM2 antibody designed to modulate microglial activity in Alzheimer’s patients.
Featured Articles Five stocks we like better than Denali Therapeutics
Receive News & Ratings for Denali Therapeutics Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Denali Therapeutics and related companies with MarketBeat.com's FREE daily email newsletter.
Takeda Ends Drug Partnership For Strategic ReasonsTakeda on Friday notified Denali Therapeutics regarding the termination of their collaboration agreement to co-develop DNL593, a progranulin replacement therapy for frontotemporal dementia.
The decision is strategic and not related to efficacy or safety data, allowing Denali to regain full control over the therapy and its intellectual property.
Biomarker Results Expected By End Of 2026“While we have greatly valued our partnership, we are pleased to regain full ownership of DNL593. We remain confident in the scientific rationale and the data generated to date, and we look forward to advancing DNL593 independently. We plan to report results from the ongoing Phase 1/2 trial by the end of 2026,” said Ryan Watts, CEO of Denali Therapeutics
Early Data Show Dose-Dependent Progranulin IncreasesEnrollment in this study was completed with a total of 40 participants with FTD-GRN.
Interim results from Part A of the Phase 1/2 study in healthy volunteers demonstrated dose-dependent increases in cerebrospinal fluid progranulin levels, consistent with robust brain delivery of DNL593.
DNL593 was generally well tolerated, and there have been no significant safety signals to date.
In December 2025, the FDA placed a clinical hold on Denali’s investigational new drug application for the Phase 1 study of DNL952 under development for Pompe disease.
The FDA requested a protocol amendment to include a lower starting dose, revised inclusion criteria, certain safety monitoring commitments, and stopping rules.
Analyst Consensus & Recent Actions: The stock carries a Buy Rating with an average price target of $34.83. Recent analyst moves include:
Morgan Stanley: Overweight (Raises Target to $42.00) (March 26) Goldman Sachs: Buy (Raises Target to $40.00) (March 26) Stifel: Buy (Raises Target to $41.00) (March 26) DNLI Price Action: Denali Therapeutics shares were down 3.73% at $19.88 at the time of publication on Monday, according to Benzinga Pro data.
Image via Shutterstock
Market News and Data brought to you by Benzinga APIs
Key Takeaways DNLI stock fell after Takeda ended its DNL593 collaboration, citing strategic priorities, not safety issues. Denali regains full ownership of DNL593 and plans to advance the therapy independently toward 2026 data. DNL593 study shows early biomarker gains; Denali now bears full development and commercialization costs. Shares of Denali Therapeutics Inc. (DNLI - Free Report) were down 6.15% on April 6, after the company announced that partner Takeda (TAK - Free Report) has decided to terminate their collaboration agreement to co-develop and co-commercialize DNL593 (PTV:PGRN) on April 3.
Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues.
Following the termination of the co-development agreement, Denali will regain full ownership of DNL593 along with its intellectual property.
Denali stock has gained 17.4% year to date compared with the industry’s growth of 0.4%.
Image Source: Zacks Investment Research
More on DNLI’s Frontotemporal Dementia-granulin CandidateDNL593 is an investigational progranulin replacement therapy designed using Denali’s Protein TransportVehicle (PTV) platform to deliver progranulin across the blood-brain barrier for the treatment of frontotemporal dementia caused by GRN mutations (FTD-GRN).
Denali plans to independently advance DNL593 and post phase I/II study results by the end of 2026.
The ongoing phase I/II study of DNL593 has completed enrollment with 40 participants diagnosed with FTD-GRN, with biomarker data expected later in 2026. Earlier interim results from healthy volunteers showed dose-dependent increases in cerebrospinal fluid progranulin levels, indicating effective brain delivery. The therapy has been generally well tolerated so far, with no major safety concerns reported.
Frontotemporal dementia is the most common form of dementia in individuals under 60. It leads to progressive decline in behavior, personality, and language or motor functions. Mutations in the GRN gene, which encodes the progranulin protein, are among the leading genetic causes of the disease. Currently, there are no approved treatments to halt or slow its progression.
Regaining full control of DNL593 is a strategic positive, as it allows Denali to capture all future value if the therapy succeeds.
However, Takeda’s exit may raise concerns. Even though the decision was not tied to safety or efficacy, the loss of a large pharma partner removes external validation and shared financial burden. Denali will now need to fund late-stage development and potential commercialization on its own, increasing capital requirements.
Denali’s Recent Drug Approval: A Major BoostLast month, Denali secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome.
The approval marks the company’s first commercial product and a potential inflection point for its long-term growth story.
The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder. It is also the first approved therapy in a new class of biologics designed to cross the blood-brain barrier by targeting the transferrin receptor.
While successful commercialization remains key, the approval of Avlayah underscores the potential of Denali’s TransportVehicle platform to address the longstanding challenge of delivering biologic therapies across the blood-brain barrier, with the goal of transforming treatment for a broad range of neurodegenerative diseases, lysosomal storage disorders, and other serious conditions affecting millions worldwide.
Denali boasts a deep pipeline. One promising asset is DNL126, being developed for Sanfilippo syndrome type A, a rare pediatric neurodegenerative disorder. DNLI is also evaluating DNL628 (OTV:MAPT) for Alzheimer’s disease.
Strategic partnerships further strengthen Denali’s development capabilities and help mitigate financial and clinical risk.
Denali is developing other candidates in partnership with Biogen (BIIB - Free Report) and Sanofi (SNY - Free Report) .
DNLI and Biogen continue co-development of BIIB122.
Biogen is leading the global phase IIb LUMA study, evaluating BIIB122's impact on disease progression in early-stage PD. Data is expected in mid-2026.
Denali is conducting the phase IIa BEACON study, specifically enrolling participants with LRRK2-associated PD, to assess how LRRK2 inhibition may impact this disease.
Sanofi is developing eclitasertib for the treatment of moderate-to-severe ulcerative colitis. Data from the phase II study is expected in the first half of the year.
Another promising asset is DNL126, being developed for Sanfilippo syndrome type A, a rare pediatric neurodegenerative disorder. DNLI is also evaluating DNL628 (OTV:MAPT) for Alzheimer’s disease.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
Denali Therapeutics has transitioned from a speculative platform to a commercial-stage rare disease company with FDA approval of AVLAYAH for Hunter syndrome. DNLI's TransportVehicle technology enables delivery of biologics across the blood-brain barrier, providing significant differentiation and commercial potential in neurodegenerative and lysosomal storage diseases. With $1.17 billion in pro-forma liquidity and a focused initial launch, DNLI is positioned for 2.8 years of runway, reducing near-term capital risk.
On May 5, 2026, Privium Fund Management B.V. disclosed a new position in Denali Therapeutics (DNLI +4.78%), acquiring 254,857 shares in an estimated $5.07 million trade based on quarterly average pricing.
What happenedAccording to an SEC filing published May 5, 2026, Privium Fund Management B.V. initiated a new holding in Denali Therapeutics (DNLI +4.78%), purchasing 254,857 shares. The estimated transaction value was $5.07 million, calculated using the average closing price for the first quarter of 2026. The quarter-end value of the new position was $4.89 million, capturing both the size of the new holding and share price changes.
What else to knowThis is a new position for Privium Fund Management B.V., representing 1.0% of 13F reportable AUM after the trade. Top five holdings after the filing:NASDAQ:TSLA: $82.53 million (17.2% of AUM)NASDAQ:SHOP: $48.28 million (10.1% of AUM)NYSE:SPOT: $32.49 million (6.8% of AUM)NASDAQ:PLTR: $29.26 million (6.1% of AUM)NASDAQ:AMZN: $26.03 million (5.4% of AUM)As of May 4, 2026, Denali Therapeutics shares were priced at $18.67, up 18.32% over the past year, underperforming the S&P 500 by 10.15 percentage points. Company overviewMetricValuePrice (as of market close May 4, 2026)$18.67Market Capitalization$3.0 billionNet Income (TTM)($512.5 million)One-Year Price Change18.32%Company snapshotDevelops therapeutic candidates for neurodegenerative diseases, including LRRK2 inhibitors for Parkinson's disease, DNL310 for Hunter syndrome, and other assets targeting ALS, MS, Alzheimer's, and lupusOperates a research-driven biopharmaceutical model and has entered into collaboration agreements with multiple pharmaceutical partnersTargets patients suffering from neurodegenerative and rare diseases, with primary collaboration partners including large pharmaceutical companiesDenali Therapeutics is a biotechnology company focused on discovering and developing innovative therapies for neurodegenerative and rare diseases. It leverages a robust pipeline of clinical-stage assets and strategic collaborations with leading pharmaceutical firms to advance its drug candidates.
Today's Change
(
4.78
%) $
1.00
Current Price
$
22.02
What this transaction means for investorsPrivium Fund Management runs hedge funds and alternative strategies with high minimums that lock out most investors. They took a $5 million swing on Denali Therapeutics during Q1, buying in as the company approached a make-or-break FDA decision.
In late March, the FDA granted accelerated approval for Denali's first commercial drug, Avlayah, which treats the neurological symptoms of Hunter syndrome, a rare pediatric disease. This is a huge deal because Denali's technology enables biologics to cross the blood-brain barrier, something most drugs can't do. The approval validates their entire TransportVehicle platform, which they're now using to develop treatments for Alzheimer's, Parkinson's, and other brain diseases.
Biotech stocks like this one are high-risk, high-reward bets on science. You're betting the FDA approves their drugs, doctors prescribe them, and the company doesn't run out of cash before generating revenue. Denali has $966 million in cash but posted a $512 million loss in 2025 while building out their commercial operations. If their platform works across multiple diseases, the upside is massive. If clinical trials fail or the market doesn't adopt Avlayah, the stock could crater.
Sara Appino has positions in Amazon, Palantir Technologies, Shopify, and Tesla. The Motley Fool has positions in and recommends Amazon, Palantir Technologies, Shopify, Spotify Technology, and Tesla. The Motley Fool recommends Denali Therapeutics. The Motley Fool has a disclosure policy.
FDA approved AVLAYAH™ (tividenofusp alfa-eknm) for treatment of Hunter syndrome (MPS II) and as first medicine to leverage transferrin receptor to cross blood-brain barrierAVLAYAH launched in U.S. with strong momentum, vibrant community engagement, and first patients treated in commercial setting in AprilBroad clinical pipeline progressing for lysosomal storage and neurodegenerative diseases, including first patient dosed with Oligonucleotide TransportVehicle™ (OTV)-enabled DNL628 (OTV:MAPT) targeting tau for Alzheimer's diseaseAdvancing DNL593 (PTV:PGRN) in Phase 1/2 study for GRN-related frontotemporal dementia after regaining full rights, with data expected by end of 2026 SOUTH SAN FRANCISCO, Calif., May 07, 2026 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the first quarter ended March 31, 2026, and provided business highlights, including the recent U.S. Food and Drug Administration (FDA) approval of AVLAYAH™ (tividenofusp alfa-eknm).
“The FDA approval of AVLAYAH is a major milestone for Denali, for the Hunter syndrome community, and for the field of biotherapeutics enabled to cross the blood-brain barrier. We are thrilled by the strong engagement with the community, seamless execution by our commercial team, and achievement of our first patient dosed in less than one month from approval,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “AVLAYAH provides validation for our TransportVehicle™ (TV) platform enabling our broad clinical portfolio for lysosomal storage and neurodegenerative diseases. We are excited about progress achieved across the portfolio, including dosing of the first patients with our Oligonucleotide TV-enabled investigational therapy DNL628 (OTV:MAPT) targeting tau for Alzheimer’s disease and advancing DNL593 (PTV:PGRN) for FTD-GRN after regaining full rights."
First Quarter 2026 and Recent Program Updates
COMMERCIAL PRODUCT
AVLAYAH (tividenofusp alfa-eknm) for Hunter syndrome (mucopolysaccharidosis type II [MPS II])
On March 25, 2026, Denali announced AVLAYAH (tividenofusp alfa-eknm) received accelerated approval for the treatment of neurologic manifestations of Hunter syndrome (MPS II) when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial. The U.S. commercial launch of AVLAYAH is underway and the first patients have received therapy. All key operational launch components are in place, including availability of commercial product through an established distribution channel and fully operational patient support hub. The major health systems and key national and regional payers have been engaged. The ongoing global Phase 2/3 COMPASS study is designed to generate confirmatory evidence and support global regulatory submissions for AVLAYAH.
CLINICAL PROGRAMS
DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA)
DNL126 is an investigational, intravenously administered, Enzyme TransportVehicle™ (ETV)-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy designed to deliver SGSH into the brain and body, with the goal of addressing the behavioral, cognitive and physical manifestations of Sanfilippo syndrome type A. The Phase 1/2 trial of DNL126 is ongoing, and start-up activities are underway for a global Phase 3 confirmatory study. Denali expects a Biologics License Application (BLA) submission and potential accelerated approval for DNL126 for Sanfilippo syndrome type A in 2027.
DNL593 (PTV:PGRN) for GRN-related frontotemporal dementia (FTD-GRN)
Denali is conducting a Phase 1/2 study of DNL593, an investigational, intravenously administered progranulin replacement therapy utilizing Denali’s Protein TransportVehicle™ (PTV) to deliver progranulin across the blood-brain barrier (BBB) and into the brain for individuals with FTD-GRN. Enrollment in the study is complete with a total of 40 participants with FTD-GRN, and results are expected by the end of 2026.
DNL628 (OTV:MAPT) for Alzheimer's disease
In March 2026, the first patient was dosed in the Phase 1b study of DNL628, which is an investigational therapy for Alzheimer’s disease and enabled by Denali’s Oligonucleotide TransportVehicle™ (OTV). DNL628 is designed to cross the BBB and reduce the tau protein by targeting the MAPT gene that encodes for tau. Denali expects data from this study in 1H 2027.
DNL952 (ETV:GAA) for Pompe disease
DNL952 is enabled by Denali’s ETV and designed to enhance delivery of the missing enzyme, GAA, into muscle tissues and across the BBB into the brain. Phase 1 study start-up activities are underway.
BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease
A clinical data readout of the global Phase 2b LUMA study of BIIB122 for early-stage Parkinson’s disease is expected in mid-2026. Denali’s Phase 2a BEACON study in individuals with Parkinson’s disease who are confirmed by genetic testing to be carriers of a pathogenic LRRK2 variant is ongoing. The LRRK2 program is being developed in collaboration with Biogen.
IND-ENABLING STAGE PROGRAMS
Denali has multiple additional programs in the IND-enabling stage including DNL921 (ATV:Abeta) for Alzheimer’s disease; DNL111 (ETV:GCase) for Parkinson’s disease and Gaucher disease; DNL622 (ETV:IDUA) for MPS I; and DNL422 (OTV:SNCA) for Parkinson’s disease. Denali is on track to submit a regulatory filing for DNL921 in the first half of 2026 to begin clinical development of this TV-enabled anti-amyloid program for Alzheimer’s disease.
Corporate Updates
As previously announced in connection with the approval of AVLAYAH, the FDA granted Denali Therapeutics a Rare Pediatric Disease Priority Review Voucher (PRV). This voucher may be used to obtain priority review for a future marketing application and can be transferred to another sponsor.
On March 27, 2026, Denali received $200 million in gross proceeds in connection with the closing of the transactions under a synthetic royalty funding agreement signed in December 2025 with Royalty Pharma Investments 2023 ICAV.
On April 3, 2026, Denali announced it received notification from Takeda of its decision to terminate the collaboration agreement between the two companies to co-develop and co-commercialize DNL593. Takeda’s decision was driven by strategic considerations and was not related to efficacy or safety data. Denali continues to advance DNL593 in the ongoing Phase 1/2 study in patients with FTD-GRN and expects results by the end of 2026 as described above.
Participation in Upcoming Investor Conferences
Bank of America Healthcare Conference 2026, May 12-14 (Las Vegas)Jefferies Global Healthcare Conference, June 2-4 (New York City)Goldman Sachs 47th Annual Global Healthcare Conference, June 8-10 (Miami)BTIG Virtual Biotechnology Conference, July 28-29 First Quarter 2026 Financial Results
Net loss was $128.4 million for the quarter ended March 31, 2026, compared to net loss of $133.0 million for the quarter ended March 31, 2025.
Total research and development expenses were $103.8 million for the quarter ended March 31, 2026, compared to $116.2 million for the quarter ended March 31, 2025. The decrease of approximately $12.4 million was primarily attributable to the timing of manufacturing of AVLAYAH commercial supply in the first quarter of 2025, as well as lower external expenses related to small molecule programs.
General and administrative expenses were $33.5 million for the quarter ended March 31, 2026, compared to $29.4 million for the quarter ended March 31, 2025. The increase of $4.1 million was primarily driven by higher personnel-related costs due to increased headcount in the first quarter of 2026, reflecting headcount additions made throughout 2025 to support post-launch activities for AVLAYAH.
Cash, cash equivalents and marketable securities were approximately $1.05 billion as of March 31, 2026.
About the Denali TransportVehicle™ Platform
The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes and oligonucleotides throughout the whole body, including the brain, by crossing the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, which are expressed at the BBB and deliver the TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the TV platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates. The TV platform has been clinically validated, with AVLAYAH™ (tividenofusp alfa-eknm) as the first FDA-approved medicine leveraging transferrin receptor to cross the BBB.
About Denali Therapeutics
Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier (BBB) using its proprietary TransportVehicle™ platform. With the first FDA-approved biologic specifically designed to cross the BBB, a clinically validated delivery platform, and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform life for people with neurodegenerative diseases, lysosomal storage disorders and other serious diseases. For more information, please visit www.denalitherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations for Denali’s TransportVehicle™ (TV) platform, including the Enzyme TransportVehicle™ (ETV) franchise, and its therapeutic and commercial potential; plans, timelines, and expectations relating to the commercial launch of AVLAYAH™ (tividenofusp alfa-eknm) and related activities; expectations related to the ongoing Phase 2/3 COMPASS study of tividenofusp alfa, including the timing and availability of data and its ability to generate confirmatory evidence and support global regulatory submissions; plans, timelines and expectations related to DNL126, including the ongoing Phase 1/2 study, the planned Phase 3 confirmatory study, the planned BLA submission, and the likelihood and timing of accelerated approval; plans, timelines and expectations related to DNL593, including the ongoing Phase 1/2 study, the timing and availability of data, and Denali’s ability to independently advance the program; plans, timelines and expectations related to DNL628, including the ongoing Phase 1b study and the timing and availability of data; plans, timelines and expectations related to DNL952 and the planned Phase 1 study; plans, timelines and expectations related to DNL151, including the ongoing Phase 2a BEACON study, and the timing and availability of data from the Phase 2b LUMA study; plans, timelines and expectations related to DNL921, including the expected timing of a regulatory filing and initiation of clinical development; plans, timelines, and expectations for IND-enabling stage programs; plans and expectations regarding Denali's Rare Pediatric Disease Priority Review Voucher; expectations regarding the Royalty Pharma funding agreement, including royalty payment obligations and milestones; plans regarding participation in upcoming investor conferences; and statements by Denali's Chief Executive Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to, uncertainties related to the FDA’s policies and accelerated approval program; risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a commercial company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; whether the current ongoing trials have been powered sufficiently to demonstrate approvability to regulatory agencies; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; discrepancies between preclinical, early-stage or preliminary clinical results and outcomes from later-stage trials; the risk that interim or topline clinical results may not be predictive of final study results or longer‑term outcomes; the occurrence of significant adverse events or other undesirable side effects; the uncertainty surrounding regulatory approvals required for commercialization in the U.S., Europe or other international jurisdictions; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and competing product candidates; Denali’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; the implementation and success of Denali’s strategic plans for its business, product candidates and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 26, 2026, and Denali’s future reports to be filed with the SEC. Except for AVLAYAH, Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.
Denali Therapeutics Inc.
Condensed Consolidated Statements of Operations
(Unaudited)
(In thousands, except share and per share amounts) Three Months Ended March 31, 2026 2025 Operating expenses: Research and development$103,846 $116,227 General and administration 33,511 29,353 Total operating expenses 137,357 145,580 Loss from operations (137,357) (145,580)Interest and other income, net 8,910 12,610 Net loss$(128,447) $(132,970)Net loss per share, basic and diluted$(0.69) $(0.78)Weighted average number of shares outstanding, basic and diluted 186,636,978 171,222,030 Denali Therapeutics Inc.
Condensed Consolidated Balance Sheets
(Unaudited)
(In thousands) March 31,
2026 December 31,
2025Assets Current assets: Cash and cash equivalents$387,626 $205,326Short-term marketable securities 600,058 662,553Prepaid expenses and other current assets 35,068 32,779Total current assets 1,022,752 900,658Long-term marketable securities 63,785 98,322Property and equipment, net 51,728 52,402Finance lease right-of-use asset 47,616 48,531Operating lease right-of-use asset 17,922 19,002Intangible asset, net 36,000 —Other non-current assets 26,220 25,939Total assets$1,266,023 $1,144,854Liabilities and stockholders' equity Current liabilities: Accounts payable$40,380 $505Accrued expenses and other current liabilities 69,776 76,745Total current liabilities 110,156 98,351Operating lease liability, less current portion 24,680 27,210Finance lease liability, less current portion 5,508 5,532Liability related to the revenue participation right agreement 199,581 —Total liabilities 339,925 131,093Total stockholders' equity 926,098 1,013,761Total liabilities and stockholders’ equity$1,266,023 $1,144,854 Investor Contact:
Laura Hansen, Ph.D. [email protected]
Key Takeaways Denali won FDA approval for Avlayah, a new Hunter syndrome therapy targeting neurological symptoms.DNLI ended Q1 with $1.05B in cash, supporting ongoing pipeline and launch activities.Denali expects mid-2026 data from BIIB122 studies in Parkinson's disease with Biogen. Denali Therapeutics (DNLI - Free Report) reported a first-quarter 2026 loss of 69 cents per share, narrower than the Zacks Consensus Estimate of a loss of 73 cents. The company had incurred a loss of 78 cents in the year-ago quarter.
In late March, Denali secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome (MPS II). The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder. It is also the first approved therapy in a new class of biologics designed to cross the blood-brain barrier by targeting the transferrin receptor. The continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory study.
Avlayah is an enzyme replacement therapy indicated for pediatric patients with MPS II, targeting neurological symptoms when initiated early. However, the drug is yet to be commercially launched in the United States, and therefore, Denali did not generate any revenues in the reported quarter. The Zacks Consensus Estimate for revenues was pegged at $10 million. The company also periodically recognizes collaboration revenues.
Following Avlayah approval, the FDA granted Denali a Rare Pediatric Disease Priority Review Voucher, which can be used to secure priority review for a future marketing application or transferred to another sponsor.
Highlights of DNLI’s Q1 ResultsResearch and development expenses decreased 11% to $103.8 million due to the timing of manufacturing of Avlayah commercial supply in the first quarter of 2025, as well as lower external expenses related to small molecule programs.
General and administrative expenses increased 14% to $33.5 million primarily due to higher personnel-related expenses resulting from increased headcount in the first quarter of 2026, reflecting staffing additions made throughout 2025 to support Avlayah’s post-launch activities.
As of March 31, 2026, cash, cash equivalents, and marketable securities amounted to approximately $1.05 billion compared with $966.2 million as of Dec. 31, 2025.
Shares of DNLI have gained 19.4% year to date against the industry’s 0.2% decline.
Image Source: Zacks Investment Research
DNLI’s Key Pipeline UpdatesDenali’s ongoing global phase II/III COMPASS study is expected to provide confirmatory data and support regulatory filings for tividenofusp alfa-eknm worldwide, including in young adult patients with Hunter syndrome. Positive outcomes from this study could further expand the drug’s commercial potential and reinforce DNLI’s position in the rare neurodegenerative disease market.
Denali is evaluating DNL126 for the treatment of Sanfilippo syndrome type A (MPS IIIA). It is an investigational intravenously administered ETV-enabled SGSH replacement therapy, being developed to target the neurological and systemic manifestations of the disease by delivering the enzyme to both the brain and body. Per DNLI, the phase I/II MPS IIIA study is ongoing, while start-up activities for a global phase III confirmatory study for this indication are also underway. A regulatory submission with potential accelerated approval is anticipated in 2027.
Denali is also developing other candidates in partnership with Biogen (BIIB - Free Report) and Sanofi (SNY - Free Report) .
Denali and Biogen continue co-development of BIIB122/DNL151.
Biogen is leading the global phase IIb LUMA study, evaluating BIIB122's impact on disease progression in early-stage Parkinson’s disease (PD). Data is expected in mid-2026. Denali is conducting the phase IIa BEACON study, specifically enrolling participants with LRRK2-associated PD to assess how LRRK2 inhibition may impact this disease.
Sanofi is developing eclitasertib for moderate to severe ulcerative colitis. Data from the phase II study is expected in the first half of the year.
Denali is also developing DNL952, an ETV-enabled therapy designed to enhance the delivery of the missing GAA enzyme to muscle tissues and across the blood-brain barrier into the brain, with phase I study start-up activities currently underway.
Last month, Denali announced that former partner Takeda (TAK - Free Report) decided to terminate their collaboration agreement to co-develop and co-commercialize DNL593 (PTV: PGRN). Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues. Following the termination of the co-development agreement, Denali regained full ownership of DNL593 along with its intellectual property.
Denali is conducting a phase I/II study evaluating DNL593, an investigational, intravenously-administered progranulin replacement therapy that uses its PTV platform to deliver progranulin across the blood-brain barrier into the brain for patients with frontotemporal dementia caused by GRN mutations. Enrollment in the study is complete with 40 participants, and results are expected by the end of 2026.
Another candidate in Denali Therapeutics’ pipeline is DNL628, an investigational OTV-enabled therapy for Alzheimer’s disease designed to cross the blood-brain barrier and reduce tau protein levels by targeting the MAPT gene. The first patient was dosed in the phase Ib study in March 2026, with data expected in the first half of 2027.
Our Take on DNLI’s PerformanceThe approval of Avlayah has significantly boosted DNLI’s growth prospects. The company’s progress with DNL126 is encouraging as well.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
DNLI’s Zacks RankDenali currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.
Analysts Say These 2 Mid-Cap Biotechs Have 2x PotentialDenali Therapeutics NASDAQ: DNLI is seeing early commercial interest for its first approved drug, AVLAYAH, following its March 24 accelerated approval for Hunter syndrome, Chief Operating Officer and Chief Financial Officer Alexander Schuth said at a Bank of America Securities conference.
Speaking with Bank of America Senior Pharmaceuticals Analyst Geoff Meacham, Schuth described the approval as a “big transition” for Denali and a significant moment for the Hunter syndrome community and for the broader field of blood-brain barrier transport.
Get Denali Therapeutics alerts:
3 Mid-Cap Biotechs Analysts Think Can DoubleAVLAYAH is indicated for the treatment of neurologic manifestations in pediatric patients with Hunter syndrome, a rare pediatric lysosomal storage disease with a severe neurodegenerative component. Schuth said traditional enzyme replacement therapy does not cross the blood-brain barrier, while Denali’s technology is designed to treat the whole body, including the brain.
Early Launch Activity Ahead of Denali’s Expectations Schuth said Denali is encouraged by the “level of engagement” and “level of interest” in AVLAYAH across age groups and levels of disease severity. He said the first commercial patients are now on therapy and clarified that these were not patients who transitioned from Denali’s clinical studies.
In one case, Schuth said a patient moved onto the drug commercially within three and a half weeks after approval through a medical exception process. He said Denali is seeing start forms but is not yet disclosing the number, because the company wants more experience converting those forms into revenue in a buy-and-bill setting.
“From an engagement and an interest perspective, I think we’re safe to say that we’re ahead of expectations,” Schuth said.
Schuth emphasized that Hunter syndrome is an ultra-rare disease but said patient identification should not be a major hurdle because enzyme replacement therapy has been available for about 20 years. He said Denali knows where U.S. patients are treated through prescription data and that the company’s field team has been in contact with every treating physician.
On reimbursement, Schuth said Denali has engaged with major national and regional payer systems. He said prior authorization and medical exception processes have gone smoothly for many early patients, while some denials have occurred as expected before formal reimbursement policies are established.
Market Opportunity and Label Expansion Schuth pointed to ELAPRASE, the current standard of care, as a benchmark, saying it generates about $700 million in annual sales. He said Denali believes AVLAYAH has advantages because it can enter the brain and treat the whole body, and he noted the drug carries a price premium over ELAPRASE.
Denali typically frames AVLAYAH and its Sanfilippo candidate DNL126 together as a potential $1 billion market opportunity, Schuth said, adding that the assumption is “quite conservative.”
Schuth said Denali does not view AVLAYAH’s label as more limited than expected. He said the label covers pediatric patients, which he estimated at about 70% of the Hunter syndrome population, and includes symptomatic and pre-symptomatic patients. He also said the restriction excluding patients under five kilograms reflects the population studied and corresponds roughly to a three-month-old child.
Denali expects the label could expand after data from the Phase 2/3 COMPASS confirmatory study, which Schuth said includes adult patients up to age 26. Denali expects data by the end of next year, and Schuth said the company would expect the pediatric limitation to be lifted if the data support it.
Sanfilippo, Pompe and the Enzyme Replacement Pipeline Schuth said Denali’s next enzyme replacement therapy program is DNL126 for Sanfilippo syndrome, or MPS IIIA. He said the company presented Phase 1/2 data in February showing a mean 80% reduction in heparan sulfate, a cerebrospinal fluid biomarker qualified by the FDA as reasonably likely to predict clinical benefit and serve as a basis for accelerated approval.
Schuth said Denali believes it has the data package to submit a biologics license application for DNL126 in 2027 and potentially achieve approval in 2027, depending on the timing of the filing.
He said Sanfilippo is roughly comparable in market size to Hunter syndrome, though the epidemiology is less well understood because there is no current standard of care. He also said there is “almost perfect overlap” between the physicians and treatment centers involved in Hunter syndrome and Sanfilippo, meaning Denali does not expect to expand its commercial team substantially if DNL126 is approved.
Denali is also preparing to begin its first clinical study in Pompe disease. Schuth said the program will test whether Denali’s transferrin receptor-based transport approach can improve distribution to muscle and bone, where current enzyme replacement therapies may have limitations.
Parkinson’s, Tau and FTD Programs Remain Key Readouts Schuth also discussed DNL151, also known as BIIB122, Denali’s LRRK2 inhibitor partnered with Biogen for Parkinson’s disease. He said Biogen is leading a 650-patient study in idiopathic Parkinson’s disease using the Unified Parkinson’s Disease Rating Scale parts 2 and 3 to measure progression.
Schuth said Denali is looking for a clinically meaningful slowing in disease progression. A second study, BEACON, is testing the drug in patients who carry LRRK2 mutations. Schuth said decisions about the program’s future should be made in the context of both studies, with readouts expected by the end of this year.
On Denali’s tau program, Schuth said Biogen’s tau readout could be informative for the broader tau hypothesis, but he argued Denali’s bloodstream-based delivery approach may offer better brain distribution than intrathecal approaches.
Schuth also reviewed DNL593, Denali’s protein transport vehicle-enabled progranulin program for frontotemporal dementia patients with progranulin deficiency. He said a Phase 1b study in 40 patients is expected to read out by the end of this year, with Denali focused primarily on lysosomal function markers. Longer term, he said reductions in neurofilament would help support moving into an efficacy study.
About Denali Therapeutics NASDAQ: DNLIDenali Therapeutics is a clinical‐stage biopharmaceutical company focused on developing therapies for neurodegenerative diseases. The company's research leverages a proprietary Blood–Brain Barrier Transport Vehicle (TV) platform designed to enable large molecules, including antibodies and enzymes, to penetrate the central nervous system. Denali's approach includes small molecules, monoclonal antibodies and gene therapy candidates aimed at key drivers of disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Among Denali's lead programs is an orally delivered leucine‐rich repeat kinase 2 (LRRK2) inhibitor for Parkinson's disease, and an anti‐TREM2 antibody designed to modulate microglial activity in Alzheimer's patients.
This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected].
Should You Invest $1,000 in Denali Therapeutics Right Now?Before you consider Denali Therapeutics, you'll want to hear this.
MarketBeat keeps track of Wall Street's top-rated and best performing research analysts and the stocks they recommend to their clients on a daily basis. MarketBeat has identified the five stocks that top analysts are quietly whispering to their clients to buy now before the broader market catches on... and Denali Therapeutics wasn't on the list.
While Denali Therapeutics currently has a Moderate Buy rating among analysts, top-rated analysts believe these five stocks are better buys.
View The Five Stocks Here
Learn the basics of options trading and how to use them to boost returns and manage risk with this free report from MarketBeat. Click the link below to get your free copy.
On May 15, 2026, ADAR1 Capital Management disclosed in an SEC filing that it bought 1,819,339 Denali Therapeutics shares, an estimated $36.20 million trade based on quarterly average pricing.
What happenedAccording to a Securities and Exchange Commission (SEC) filing dated May 15, 2026, ADAR1 Capital Management, increased its position in Denali Therapeutics (DNLI +4.78%) by 1,819,339 shares during the first quarter of 2026. The estimated transaction value was $36.20 million, based on the average unadjusted closing price for the quarter. The quarter-end valuation for the position rose by $35.07 million, a figure that includes both additional shares and market price changes.
What else to knowThis buy brings the Denali Therapeutics stake to 2.12% of ADAR1’s reported equity assets after the first quarter.Top holdings after the filing:NASDAQ: ABVX: $155.22 million (9.4% of AUM)NASDAQ: PTGX: $104.78 million (6.4% of AUM)NASDAQ: ROIV: $91.02 million (5.5% of AUM)NASDAQ: IMVT: $66.55 million (4.0% of AUM)NYSEMKT: SPY: $49.39 million (3.0% of AUM)As of May 17, 2026, Denali Therapeutics shares were priced at $18.62, up 31.5% over the past year, outperforming the S&P 500 by 6.29 percentage points.Company OverviewMetricValueMarket Capitalization$2.96 billionEmployees443Net Income (TTM)$-508.02 millionPrice (as of market close 2026-05-15)$18.62Company SnapshotDevelops therapeutic candidates for neurodegenerative diseases, including Parkinson's disease, Hunter syndrome, ALS, multiple sclerosis, Alzheimer's disease, and lupus, with several candidates in Phase I and II clinical trials.Operates a biotechnology business model focused on drug discovery and development, generating revenue primarily through research collaborations and licensing agreements with major pharmaceutical partners.Targets healthcare providers, pharmaceutical companies, and patients affected by neurodegenerative and rare diseases in the United States and globally.Denali Therapeutics is a clinical-stage biopharmaceutical company specializing in the development of innovative therapies for neurodegenerative diseases. The company's strategy emphasizes advancing a diversified pipeline through strategic collaborations with leading pharmaceutical firms.
Today's Change
(
4.78
%) $
1.00
Current Price
$
22.02
What this transaction means for investorsInvesting in a biotech that just got its first drug approved is betting the science behind that success can be repeated across multiple diseases. Hedge fund ADAR1 Capital Management made that bet with a $36 million Denali Therapeutics position in Q1.
Denali recently achieved a major milestone with FDA approval for its first commercial drug, treating a rare brain disease. What makes this significant is the technology behind it. The company developed a platform that solves a longstanding medical problem: getting drugs into the brain. Most therapies can't cross the protective barrier around the brain, limiting treatment options for neurological diseases.
The company has substantial cash reserves and is developing treatments for Alzheimer's, Parkinson's, and other brain conditions using the same underlying technology.
For average investors, this is high-risk, high-reward investing. If the platform proves it can deliver multiple successful drugs, the upside is enormous. If future candidates fail or the technology doesn't work as broadly as hoped, the stock could struggle despite the initial success.
Sara Appino has no position in any of the stocks mentioned. The Motley Fool has positions in and recommends Denali Therapeutics. The Motley Fool recommends Protagonist Therapeutics and Roivant Sciences. The Motley Fool has a disclosure policy.
Key Takeaways Denali and Biogen will stop BIIB122 development after a phase IIb Parkinson's study miss.DNLI will continue the BEACON study in Parkinson's patients with pathogenic LRRK2 variants.Avlayah FDA approval boosted Denali's outlook as pipeline and late-stage programs advance. Shares of Denali Therapeutics, Inc. (DNLI - Free Report) were down 8% in after-market trading on May 21, after the company and partner Biogen (BIIB - Free Report) announced disappointing top-line results from a mid-stage study evaluating BIIB122 (DNL151) in individuals with early-stage Parkinson’s disease.
The study did not meet its primary or secondary endpoints.
Consequently, Biogen and Denali will discontinue development of BIIB122 in idiopathic Parkinson’s disease.
More on BIIB & DNLI’s Parkinson’s StudyLUMA was a phase IIb, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of BIIB122 in 648 patients aged 30 to 80 with early-stage Parkinson’s disease. The study was led by Biogen.
Participants received either BIIB122 or placebo for at least 48 weeks and up to 144 weeks. The study enrolled patients both with and without pathogenic LRRK2 variants and was designed to assess whether LRRK2 inhibition could target the underlying biology of Parkinson’s disease.
The study results showed that BIIB122 failed to slow the progression of Parkinson’s disease compared with placebo, missing the primary endpoint of time to confirmed worsening on the modified MDS-UPDRS Part II and III combined score. The study also failed to demonstrate meaningful benefit across secondary endpoints.
However, exploratory biomarker analyses demonstrated more than 90% inhibition of peripheral LRRK2 kinase activity and up to a 30% reduction in phosphorylated Rab10, a CSF biomarker of LRRK2 activity, in a sub-study. BIIB122 maintained expected concentrations in both blood and CSF throughout the trial and was generally well tolerated with an acceptable safety profile.
Following these findings, Biogen and Denali plan to discontinue development of BIIB122 for idiopathic Parkinson’s disease.
Nonetheless, Denali will continue independently advancing the phase IIa BEACON study on evaluating the small molecule inhibitor in patients carrying pathogenic LRRK2 variants.
Data from the BEACON study is expected in the first half of 2027. The trial is being led by Denali and funded through a Collaboration and Development Funding Agreement with a third party.
Road Ahead for DenaliIn October 2020, the company entered into collaboration agreements with Biogen covering co-development and co-commercialization of its LRRK2 inhibitor program, along with options for select TransportVehicle (TV)-based programs, including an amyloid beta program. The agreements were later amended in August 2023 and July 2024.
The disappointing results for the LUMA study cloud the successful development of this program.
Shares of DNLI have gained 10.6% year to date while the industry’s price movement remained flat.
Image Source: Zacks Investment Research
In late March, Denali secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome (MPS II). The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder.
The approval for Avlayah has significantly boosted DNLI’s growth prospects.
Denali is evaluating DNL126 for the treatment of Sanfilippo syndrome type A (MPS IIIA). It is an investigational intravenously administered ETV-enabled SGSH replacement therapy, being developed to target the neurological and systemic manifestations of the disease by delivering the enzyme to both the brain and body.
Per DNLI, the phase I/II MPS IIIA study is ongoing, while start-up activities for a global phase III confirmatory study for this indication are also underway. A regulatory submission with potential accelerated approval is anticipated in 2027.
Denali has also collaborated with other pharma giants like Sanofi (SNY - Free Report) and Takeda (TAK - Free Report) to develop other candidates. Partner Sanofi is developing eclitasertib for moderate to severe ulcerative colitis.
In April 2026, Denali announced that partner Takeda had decided to terminate their collaboration for DNL593 (PTV:PGRN) in frontotemporal dementia associated with GRN mutations (FTD-GRN).
The termination, effective 60 days after notice, will return full rights to the program to Denali. Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
Denali Therapeutics (DNLI) maintains a "Strong Buy" rating following FDA Accelerated Approval of AVLAYAH for Hunter Syndrome and robust pipeline momentum. Company's DNL593 for FTD-GRN is differentiated by restoring both extracellular and lysosomal PGRN; phase 1/2 data readout expected by end of 2026. AVLAYAH's full approval depends on confirmatory COMPASS study results; commercial performance remains unproven post-April 2026 launch.
