Denali Therapeutics Announces Key Anticipated Milestones and Priorities for 2026 Including Commercial Launch of Tividenofusp Alfa for Hunter Syndrome

Rhea-AI Summary

Denali Therapeutics (NASDAQ: DNLI) outlined 2026 priorities focused on commercial launch preparation for tividenofusp alfa for Hunter syndrome, with a PDUFA target date of April 5, 2026. The company highlighted multiple anticipated clinical readouts and study initiations across TV-enabled and small-molecule programs, including Phase 1b start for DNL628 (OTV:MAPT) and Phase 1 start for DNL952 (ETV:GAA).

Recent milestones include a NEJM publication of tividenofusp data, completion of key enrollments, FDA lift of the clinical hold for DNL952, ~$872.9M cash as of Sept 30, 2025, a ~$200M equity financing, and a royalty funding agreement up to $275M.

Positive

• PDUFA target date set for April 5, 2026 for tividenofusp alfa
• Open-label tividenofusp results published in NEJM (Jan 1, 2026)
• FDA lifted clinical hold on DNL952, allowing Phase 1 to proceed
• Cash and liquidity of approximately $872.9M as of Sept 30, 2025 plus ~$200M equity raise

Negative

• Completed $200M equity financing may dilute existing shareholders
• Royalty funding agreement up to $275M could encumber future tividenofusp net sales

Key Figures

PDUFA date April 5, 2026 Tividenofusp alfa BLA under FDA accelerated approval pathway

Cash balance $872.9M Cash, cash equivalents and marketable securities as of Sept 30, 2025

Equity financing proceeds $200M Gross proceeds from December 2025 equity financing

Royalty funding potential $275M Proceeds up to $275M from Royalty Pharma funding agreement

WORLDSymposium dates Feb 3–6, 2026 Planned presentation of initial DNL126 Phase 1/2 data

JPM presentation time Jan 13, 2026, 1:30 p.m. PDT Corporate presentation at 44th J.P. Morgan Healthcare Conference

Market Reality Check

$16.95 Last Close

Volume Volume 1,605,164 is roughly in line with 20-day average 1,644,595 (relative volume 0.98). normal

Technical Shares at 16.02, trading above the 200-day MA of 15.10 but still 34.2% below the 52-week high.

Peers on Argus

DNLI was down 1.54% while close peers showed mixed moves: AGIO +1.03%, IDYA +3.68%, BLTE slightly higher, FOLD flat, and TVTX down 5.15%, suggesting largely stock-specific dynamics.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 30	Clinical data publication	Positive	-1.0%	NEJM Phase 1/2 tividenofusp data supporting FDA Priority Review.
Dec 10	Equity offering pricing	Negative	-10.6%	Priced stock and pre-funded warrant offering targeting ~$200M proceeds.
Dec 09	Equity offering proposal	Negative	-0.1%	Proposed underwritten offering of $200M with 30-day upsize option.
Dec 04	Royalty funding deal	Positive	+6.8%	$275M synthetic royalty deal on future tividenofusp alfa net sales.
Nov 06	Quarterly earnings update	Positive	+4.2%	Q3 2025 results plus PDUFA extension and pipeline progress updates.

Pattern Detected

Recent history shows the stock usually reacting in line with news tone, with only one notable divergence on positive clinical publication news.

Recent Company History

Over the past few months, Denali reported Q3 2025 results with cash of $872.9M and a net loss of $126.9M, secured a $275M royalty funding agreement tied to tividenofusp alfa, and executed a roughly $200M equity offering. Clinical momentum included NEJM Phase 1/2 data for tividenofusp alfa supporting a PDUFA date of April 5, 2026. Today’s milestone-rich 2026 outlook builds directly on these financing and clinical foundations.

Market Pulse Summary

The stock moved +7.4% in the session following this news. A strong positive reaction aligns with Denali’s detailed 2026 roadmap, which includes the potential U.S. accelerated approval of tividenofusp alfa with a PDUFA date of April 5, 2026 and multiple Phase 1–2 readouts. Recent financing of about $200M plus up to $275M in royalty funding reinforced liquidity. However, past equity offerings and concentrated expectations around a single lead asset could introduce reversal risk.

Key Terms

biologics license application regulatory

"regulatory decision on the Biologics License Application (BLA) for tividenofusp alfa"

A biologics license application is a formal request submitted to regulatory authorities seeking approval to market a new biological medicine, such as vaccines or treatments made from living organisms. It is a comprehensive review process that evaluates the safety, effectiveness, and manufacturing quality of the product. For investors, receiving approval signals that a biological therapy can be sold to the public, potentially leading to revenue growth and market success.

accelerated approval pathway regulatory

"under the U.S. Food and Drug Administration (FDA) accelerated approval pathway"

The accelerated approval pathway is a process that allows new medicines to be approved more quickly based on early evidence that they may be effective, rather than waiting for full proof. This can help patients access promising treatments faster, but it also means ongoing studies are needed to confirm the benefits. For investors, it highlights potential faster market entry and earlier revenue opportunities, along with some uncertainty about long-term outcomes.

prescription drug user fee act regulatory

"with a Prescription Drug User Fee Act (PDUFA) target action date of April 5, 2026"

A federal program that lets drug makers pay fees to the U.S. regulator to fund and speed up the review of new medicines and label changes. Investors care because it affects how quickly a drug can move from testing to market and how predictable approval timelines and regulatory interactions are — like buying a faster lane at a busy checkpoint that can reduce uncertainty about a product’s commercial timing.

phase 1/2 medical

"Results from the open-label Phase 1/2 clinical trial of tividenofusp alfa"

Phase 1/2 is a combined early-stage clinical trial that first tests a new drug or treatment for safety and the right dose, then quickly expands to check if it shows any signs of working in patients. For investors, results from a Phase 1/2 study offer an early read on both risk and potential reward—like a prototype test that both confirms a product won’t harm users and suggests whether it could sell—helping guide valuation and development decisions.

clinical trial application regulatory

"Denali today announced that the Clinical Trial Application (CTA) for the Phase 1b study"

An application submitted to a regulatory authority requesting formal permission to begin testing a new drug, medical device, or treatment in humans. Like asking for a building permit before construction, it summarizes safety data, plans for how the study will be run, and monitoring procedures; investors watch these filings closely because approval lets a program move from lab research to clinical testing, reducing uncertainty and creating value-driving milestones.

investigational new drug regulatory

"the U.S. FDA has lifted the clinical hold on the Investigational New Drug (IND) application"

An investigational new drug is a medication that is still being tested in clinical trials to determine if it is safe and effective for treating a specific condition. For investors, it represents a potential breakthrough that could lead to a new treatment and significant financial gains if successful, but also carries risks since it has not yet been approved for widespread use.

phase 2b medical

"The global Phase 2b LUMA study of BIIB122 completed enrollment"

Phase 2b is a stage in the development of a new medicine or treatment where researchers test its effectiveness and safety in a larger group of people. This step helps determine whether the treatment works well enough to move forward and if it has manageable side effects, which is important for investors because successful results can lead to potential approval and market opportunity.

phase 1b medical

"the Clinical Trial Application (CTA) for the Phase 1b study of DNL628 has been approved"

"Phase 1b" is an early stage in testing a new medical treatment or vaccine, where it is given to a small group of people to evaluate its safety and determine the right dose. For investors, this phase signals progress in development, indicating the treatment is advancing through initial safety checks, which can influence expectations for future success and potential market impact.

AI-generated analysis. Not financial advice.

• Preparing for FDA approval and commercial launch of tividenofusp alfa, Denali’s TransportVehicle™ (TV)-enabled investigational therapy for Hunter syndrome
• Expecting multiple clinical data readouts from pipeline programs including for Sanfilippo syndrome Type A (ETV:SGSH), granulin-related frontotemporal dementia (PTV:PGRN) and Parkinson’s disease (LRRK2 inhibitor)
• Planning for initiation of first-in-human clinical studies with TV-enabled therapeutics for Alzheimer’s disease (OTV:MAPT, ATV:Abeta) and Pompe disease (ETV:GAA)
• Continuing to strengthen leadership in transferrin receptor (TfR)-enabled and blood-brain barrier crossing therapeutics with continued advancement of enzyme, oligonucleotide and antibody programs
  
  

SOUTH SAN FRANCISCO, Calif., Jan. 06, 2026 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), today announced key anticipated milestones and priorities for 2026 across its portfolio of investigational therapies for neurodegenerative diseases, lysosomal storage disorders and other serious diseases. Chief Executive Officer Ryan Watts, Ph.D., will highlight these priorities during a corporate presentation at the 44th Annual J.P. Morgan Healthcare Conference on Tuesday, January 13, at 1:30 p.m. PDT.

“2026 is a defining year for Denali as we prepare to deliver our first TV-enabled medicine to patients,” said Dr. Watts. “We are on the cusp of launching tividenofusp alfa, which we believe will establish a new standard of care for people living with Hunter syndrome and mark the first commercial validation of our platform. In addition, we expect multiple clinical data readouts across our portfolio and plan to advance two TV-enabled programs into clinical studies for Alzheimer’s disease and a program for Pompe disease. As pioneers in TfR-enabled therapeutics, we are committed to advancing a new generation of transformative medicines with the potential to enhance and enable delivery of biotherapeutics throughout the whole body, including the brain.”

2026 Outlook

Expected progress and key milestones across Denali’s portfolio of TV-enabled and small molecule programs in 2026 are summarized below.

CLINICAL PROGRAMS

Tividenofusp alfa (DNL310, ETV:IDS) for Hunter syndrome (MPS II)

Denali is preparing for commercial launch in anticipation of a regulatory decision on the Biologics License Application (BLA) for tividenofusp alfa under the U.S. Food and Drug Administration (FDA) accelerated approval pathway with a Prescription Drug User Fee Act (PDUFA) target action date of April 5, 2026. Results from the open-label Phase 1/2 clinical trial of tividenofusp alfa were published in the January 1, 2026 issue of The New England Journal of Medicine. The ongoing global Phase 2/3 COMPASS study is expected to generate confirmatory evidence and support global regulatory submissions; enrollment in Cohort A (neuronopathic participants) was completed in December 2025.

DNL126 (ETV:SGSH) for Sanfilippo syndrome Type A (MPS IIIA)

Denali will present initial clinical data from the fully enrolled, ongoing Phase 1/2 study of DNL126 at the 2026 WORLDSymposium^TM (February 3-6, 2026). The Phase 1/2 study is designed to support an accelerated approval path in Sanfilippo syndrome Type A. Planning for a global Phase 3 confirmatory study is ongoing.

TAK-594/DNL593 (PTV:PGRN) for GRN-related frontotemporal dementia (FTD-GRN)

The Phase 1/2 study of TAK-594/DNL593 is ongoing with screening closed in Cohort B. Initial FTD-GRN patient data are expected in 2026. The program is being developed in collaboration with Takeda.

DNL628 (OTV:MAPT) for Alzheimer’s disease

DNL628 is enabled by Denali’s Oligonucleotide TransportVehicle™ (OTV) and is designed to cross the blood-brain barrier and reduce the tau protein by targeting the MAPT gene that encodes for tau. Denali today announced that the Clinical Trial Application (CTA) for the Phase 1b study of DNL628 has been approved and study start-up activities are underway.

DNL952 (ETV:GAA) for Pompe disease

DNL952 is enabled by Denali’s Enzyme TransportVehicle^TM (ETV) and designed to enhance delivery of the missing enzyme, GAA, into muscle tissues and across the blood-brain barrier into the brain. Denali today announced that the U.S. FDA has lifted the clinical hold on the Investigational New Drug (IND) application for DNL952, and Denali will proceed with the Phase 1 study.

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease

The global Phase 2b LUMA study of BIIB122 completed enrollment of participants with early-stage Parkinson’s disease in 2025, with a clinical readout expected in 2026. Denali’s Phase 2a BEACON study in LRRK2-associated Parkinson’s disease remains ongoing. The LRRK2 program is being developed in collaboration with Biogen.

SAR443122/DNL758 (eclitasertib; small molecule RIPK1 inhibitor) for ulcerative colitis

The Phase 2 study of eclitasertib in participants with moderate to severe ulcerative colitis is expected to have results in the first half of 2026. The program is being developed by Sanofi.

IND-ENABLING STAGE PROGRAMS

The following programs are in IND-enabling stage: 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.

PARTNERSHIPS

Denali has active collaborations with Biogen for BIIB122/DNL151 in Parkinson’s disease and with Takeda for TAK-594/DNL593 in FTD-GRN, both with 50/50 U.S. commercial rights. Denali also stands to receive royalty payments for SAR443122/DNL758, which is licensed to Sanofi and in development for ulcerative colitis.

FINANCIAL OUTLOOK

As of September 30, 2025, Denali had approximately $872.9 million in cash, cash equivalents and marketable securities. In December 2025, Denali completed an equity financing with gross proceeds of approximately $200 million and announced a royalty funding agreement with Royalty Pharma based on future net sales of tividenofusp alfa with proceeds up to $275 million.

KEY ANTICIPATED 2026 MILESTONES

Program	Indication	Expected Milestone	Timing
Tividenofusp alfa (ETV:IDS)	MPS II (Hunter syndrome)	US Accelerated Approval	1H
DNL126 (ETV:SGSH)	MPS IIIA (Sanfilippo syndrome type A)	Phase 1/2 data	1H
DNL628 (OTV:MAPT)	Alzheimer’s disease	Phase 1b study initiation	1H
DNL952 (ETV:GAA)	Pompe disease	Phase 1 study initiation	1H
DNL151 / BIIB122	Parkinson’s disease	Phase 2b LUMA data	1H
DNL921 (ATV:Abeta)	Alzheimer’s disease	Phase 1/1b study initiation	1H
DNL126 (ETV:SGSH)	MPS IIIA (Sanfilippo syndrome type A)	Phase 3 study initiation	2H
DNL593 (PTV:PGRN)	FTD-GRN	Phase 1/2 data	2H

Webcast details for Denali’s presentation at the 44th Annual J.P. Morgan Healthcare Conference

A live and archived webcast of the Denali presentation during the J.P. Morgan Conference on Tuesday, January 13, 2026, at 1:30 p.m. PDT will be available on the Events page under the Investor section of the Denali website at https://investors.denalitherapeutics.com/events.

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 the lives of people living with neurodegenerative, lysosomal storage and other serious diseases. For more information, please visit www.denalitherapeutics.com.

Cautionary Note Regarding 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 future results of operations and financial position of Denali Therapeutics Inc. (“Denali” or the “Company”); Denali’s business strategy and business plans, including expected key milestones for Denali's therapeutic portfolio in 2026 and beyond and Denali’s ability to execute on its commercial strategies; plans, timelines, expectations related to Denali's TransportVehicle^TM (TV) platform and its therapeutic and commercial potential; plans, timelines, and expectations relating to tividenofusp alfa (DNL310), including the timing, likelihood, and scope of regulatory approvals and commercial launch, the establishment of tividenofusp alfa as standard of care in MPS II,   the enrollment of the Phase 2/3 COMPASS study, and the likelihood of the Phase 2/3 COMPASS data to support confirmatory evidence for global regulatory submissions and approval; plans, timelines, and expectations related to DNL126, including the timing and availability of data from the Phase 1/2 study to support an accelerated approval path in MPS IIIA and the timing to initiate a Phase 3 study; plans and expectations regarding DNL593, including the ongoing Phase 1/2 study and the timing for the Phase 1/2 study data; plans, timelines, and expectations related to DNL628 (OTV:MAPT), including the Phase 1b study timing; plans, timelines, and expectations related to DNL952 (ETV:GAA), including the Phase 1 study timing; plans, timelines, and expectations related to DNL151, including the timing of availability of clinical data from the ongoing Phase 2b LUMA study and the ongoing Phase 2a BEACON study; plans, timelines, and expectations related to DNL758, including the timing for results of the Phase 2 study; plans, timelines, and expectations related to DNL921, including the timing of the Phase 1/1b study initiation; expectations regarding Denali's leadership in developing TfR-enabled and BBB-crossing therapeutics; expectations regarding Denali’s preclinical studies and the timing and likelihood of advancement of additional programs to clinical studies; Denali's third-party collaborations, commercial rights, and potential royalties; Denali's financial outlook, cash position, and potential cash proceeds based on a royalty funding agreement; and statements made by Denali’s Chief Executive Officer. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to: uncertainties related to the FDA’s policies and accelerated approval program, including risks that the PDUFA action date may be extended and the FDA may not approve tividenofusp alfa; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; Denali’s dependence on successful development and commercialization of its BBB platform technology and TV-enabled product candidates; Denali’s ability to initiate and enroll patients in its current and future clinical trials; Denali’s ability to conduct or complete clinical trials on expected timelines; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials and commercial products; the potential for clinical trial results to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities, or other undesirable side effects; the risk that results from early clinical biomarker studies will not translate to clinical benefit in late clinical studies; the risk that product candidates may not receive regulatory approval necessary to be commercialized; 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; and other risks and uncertainties. In light of these risks, uncertainties, and assumptions, the forward-looking statements in this press release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. No Denali product candidates have been approved by any health authority for any use. Information regarding additional risks and uncertainties may be found in Denali’s Annual and Quarterly Reports filed on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 27, 2025, and November 6, 2025, respectively, and Denali’s future reports to be filed with the SEC. 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.

Investor Contact:
Laura Hansen, Ph.D.
hansen@dnli.com

Media Contact:
Erin Patton
epatton@dnli.com

FAQ

What is the PDUFA date for Denali's tividenofusp alfa (DNLI)?

The PDUFA target action date is April 5, 2026.

Has Denali published clinical results for tividenofusp alfa (DNLI)?

Yes; results from the open-label Phase 1/2 trial were published in The New England Journal of Medicine on Jan 1, 2026.

When will Denali present its 2026 priorities at J.P. Morgan and where can I watch (DNLI)?

Denali will present on Jan 13, 2026 at 1:30 p.m. PDT; a live and archived webcast is on the company's investor Events page.

What near-term clinical starts and readouts are expected for DNLI in 1H 2026?

Expected 1H 2026 events include potential US accelerated approval decision for tividenofusp, Phase 1b initiation for DNL628, Phase 1 start for DNL952, and Phase 2b LUMA data for the LRRK2 program.

How strong is Denali's balance sheet going into 2026 (DNLI)?

As of Sept 30, 2025, Denali reported approximately $872.9M in cash and equivalents and completed a ~$200M equity financing in Dec 2025.

What is the impact of Denali's royalty funding agreement tied to tividenofusp (DNLI)?

Denali announced a royalty funding agreement for future net sales of tividenofusp with proceeds of up to $275M, which would impact future product economics.