Denali Therapeutics Announces Phase 1b Study by Partner Sanofi of RIPK1-Inhibitor DNL758 (SAR443122) in COVID-19 Patients

Rhea-AI Summary

Denali Therapeutics (NASDAQ: DNLI) has announced the commencement of dosing for DNL758 (SAR443122) in a Phase 1b trial aimed at assessing its safety and efficacy in patients with severe COVID-19. Partnered with Sanofi, DNL758 is a small molecule inhibitor of RIPK1, designed to mitigate the immune response to SARS-CoV-2. The trial seeks to reduce tissue damage from inflammation, potentially improving recovery rates. Sanofi oversees the trial's development and financing, while Denali will receive milestone payments and royalties from product sales.

Positive

• DNL758 (SAR443122) is being evaluated in a Phase 1b trial for severe COVID-19, potentially addressing critical health needs.
• Successful dosing of DNL758 may lead to milestone payments and royalties for Denali, enhancing future revenue.

Negative

• The trial's success remains uncertain, with inherent risks associated with clinical development.
• Dependence on Sanofi for execution and commercialization of DNL758 presents risks if the partnership is terminated.

• Dosing of DNL758 (SAR443122) has commenced in a randomized, double-blind, placebo-controlled Phase 1b trial to evaluate safety and effect on the immune system in severe COVID-19
• DNL758, discovered by Denali and partnered with Sanofi, is a small molecule inhibitor of RIPK1 that does not cross the blood-brain barrier, and is being developed for patients with peripheral inflammatory diseases

SOUTH SAN FRANCISCO, Calif., July 29, 2020 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (“BBB”) for neurodegenerative diseases, today announced that its partner Sanofi has commenced dosing of DNL758, a peripherally-restricted small molecule inhibitor of RIPK1, in a Phase 1b study in hospitalized adult patients with severe COVID-19 lung disease.

RIPK1, receptor-interacting serine/threonine-protein kinase 1, is a critical signaling protein in the TNF receptor pathway, which regulates inflammation and cell death in tissues throughout the body. The scientific rationale in treating severe COVID-19 with a RIPK1 inhibitor compound is to attenuate the exaggerated immune response to the SARS-CoV-2 viral infection and thereby limit potential tissue damage resulting from excessive inflammation and aim to improve patient recovery.

“We know that inhibition of RIPK1, a known target in the TNF-pathway, can significantly modulate the body’s immune response," said Ryan Watts, Ph.D., CEO. “Our partner Sanofi is expanding its clinical investigation of DNL758 into patients with severe COVID-19. We are proud to stand with Sanofi in this effort, with the aim to contribute solutions in the fight against this terrible pandemic.”

Denali and Sanofi entered a broad partnership in October 2018 for the global development and commercialization of RIPK1 inhibitors. Beyond COVID-19, the partners are currently investigating DNL788 for CNS indications and DNL758 for peripheral inflammatory indications. Sanofi is responsible for the development and commercialization of DNL758, and covers all costs related to DNL758, and Denali is entitled to receive development and sales milestone payments and royalties on product sales.

Further information on the Phase 1b clinical study with DNL758/SAR443122 for COVID-19 (study number NCT04469621) can be accessed on the ClinicalTrials.gov website or by clicking here.

About Denali

Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases. Denali Therapeutics pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB and guiding development through biomarkers that demonstrate target and pathway engagement. Denali Therapeutics is based in South San Francisco. For additional information, please visit http://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, plans, timelines and expectations related to DNL758 by both Denali and Sanofi; expectations regarding the dosing of DNL758 in a Phase 1b study in hospitalized adult patients with severe COVID-19 lung disease and potential results; 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: any and all risks to Denali’s business and operations caused directly or indirectly by the evolving COVID-19 pandemic; Denali’s early stages of clinical drug development; Denali’s and its partners’ ability to complete the development and, if approved, commercialization of its product candidates; Denali’s and its partners’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of the Sanofi collaboration agreement; Denali’s dependence on successful development of its BBB platform technology; Denali’s and its partners’ ability to conduct or complete clinical trials on expected timelines; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates and blood-brain barrier platform technology; and other risks and uncertainties, including those described in Denali’s most recent Annual Report on Form 10-K, most recent Quarterly Report on From 10-Q and Denali’s future reports to be filed with the SEC. The forward-looking statements in this press release are based on information available to Denali as of the date hereof. Denali disclaims any obligation to update any forward-looking statements, except as required by law.

Denali Contact
Morgan Warners
(202) 295-0124
mwarners@gpg.com

Sanofi Contact
Ashleigh Koss
(908) 981-8745
Ashleigh.Koss@sanofi.com

FAQ

What is the purpose of the Phase 1b trial for DNL758 (DNLI)?

The trial aims to evaluate the safety and immune effects of DNL758 in patients with severe COVID-19.

When did the dosing of DNL758 begin in the COVID-19 trial?

Dosing for the trial commenced recently, as announced on July 29, 2020.

How does DNL758 work in treating COVID-19?

DNL758 is a small molecule inhibitor of RIPK1, designed to modulate the immune response and reduce inflammation caused by the COVID-19 virus.

What are the implications for Denali (DNLI) regarding DNL758's development?

Denali stands to gain milestone payments and royalties if DNL758 successfully advances in development and commercialization.

What risks are associated with the DNL758 clinical trial?

There are uncertainties related to clinical trials, regulatory approvals, and the reliance on Sanofi for further development.