eclitasertib (SAR443122) / Denali Therap, Sanofi, Harvard University - LARVOL DELTA

RESOLUTE: Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis (clinicaltrials.gov) - P2 | N=182 | Recruiting | Sponsor: Sanofi | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Eclitasertib: Data from P2 RESOLUTE trial (NCT05588843) for moderate to severe ulcerative colitis in 2026 (Sanofi) - Q4 & FY2024 Results

P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Harnessing dual-mode RIPK1 ligands for cross-species anti-necroptosis inhibitor compounds. (PubMed, Bioorg Med Chem Lett) - "Using Eclitasertib as a starting point, and applying our previous, published knowledge regarding cyclic malonamides, we successfully identified a library of active compounds. The active enantiomer of the most balanced and promising compound was subjected to pharmacokinetics and in vivo hypothermia study in mice."

Journal • Inflammation • CDK7 • RIPK1

Eclitasertib: Data from P2 RESOLUTE trial (NCT05588843) for moderate to severe ulcerative colitis in 2025 (Sanofi) - Q1 2024 Results

P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study. (PubMed, Respir Res) - P1b | "Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo."

Clinical • Immunomodulating • Journal • P1 data • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CDK7 • CRP • RIPK1

Denali Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Business Highlights (GlobeNewswire) - "Sanofi is conducting the Phase 2 trial of SAR443122/DNL758 in UC....There was no collaboration revenue for the quarter ended December 31, 2023, compared to $10.3 million for the quarter ended December 31, 2022. Collaboration revenue was $330.5 million for the year ended December 31, 2023, compared to $108.5 million for the year ended December 31, 2022. The decrease in collaboration revenue of $10.3 million for the quarter ended December 31, 2023, compared to the comparative period in the prior quarter was primarily due to a decrease of revenue earned under the Sanofi Collaboration of $10.0 million for a milestone triggered in December 2022 upon first patient dosed in a Phase 2 study of SAR443122/DNL758 in individuals with UC."

Commercial • Trial status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Denali Therapeutics Announces Key Anticipated 2024 Milestones and Priorities to Further Advance Its Therapeutics Portfolio for Neurodegeneration and Lysosomal Storage Diseases (GlobeNewswire) - "Eclitasertib (SAR443122/DNL758) (Peripheral RIPK1 Inhibitor): Ulcerative colitis (UC)...2024 expected progress and milestones: Continue Phase 2 UC study."

Trial status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis (clinicaltrials.gov) - P2 | N=182 | Recruiting | Sponsor: Sanofi | Trial completion date: Apr 2026 ➔ Sep 2026 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2 | N=78 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2 | N=78 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Jun 2023 | Trial primary completion date: Sep 2023 ➔ May 2023

Enrollment closed • Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Sanofi | Trial completion date: Jul 2023 ➔ Apr 2024 | Trial primary completion date: Jun 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Denali Therapeutics Announces Key Anticipated 2023 Milestones for Its Therapeutic Portfolio for Neurodegeneration and Lysosomal Storage Diseases (GlobeNewswire) - "SAR443122/DNL758 (peripherally-restricted RIPK1 inhibitor): CLE and UC...2023 expected progress and milestones:...Continued recruitment of participants with ulcerative colitis in the Phase 2 study."

Enrollment status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis (clinicaltrials.gov) - P2 | N=182 | Recruiting | Sponsor: Sanofi

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Sanofi | Trial completion date: Mar 2023 ➔ Jul 2023 | Trial primary completion date: Feb 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Denali Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Business Highlights (GlobeNewswire) - "SAR443122/DNL758 (peripherally-restricted RIPK1 inhibitor): CLE, UC...Announced that Sanofi plans to initiate a Phase 2 trial of SAR443122 in ulcerative colitis (UC)."

New P2 trial • Inflammatory Bowel Disease • Ulcerative Colitis

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2; N=88; Recruiting; Sponsor: Sanofi; Trial completion date: May 2022 ➔ Dec 2022; Trial primary completion date: Apr 2022 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

[VIRTUAL] Late Breaking Abstract - Immunomodulatory and clinical effects of RIPK1 inhibitor SAR443122 in patients with severe COVID-19 (ERS 2021) - P1b | "These preliminary results indicate the need for a larger confirmatory trial to further assess clinically significant effects."

Clinical • Late-breaking abstract • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CDK7 • CRP • CXCL8 • IL6 • RIPK1

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2; N=88; Recruiting; Sponsor: Sanofi; Trial completion date: Jan 2022 ➔ May 2022; Trial primary completion date: Dec 2021 ➔ Apr 2022

Clinical • Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Ministry of Food and Drug Safety approved 26 clinical trials last week … 3 cases of phase 3, 7 cases of viability [Google translation] (Health Korea News) - "The Ministry of Food and Drug Safety has approved a total of 26 clinical trials over the past week...IQVIA Korea is conducting a phase 3 clinical trial of 'OPT-302', a treatment for neovascular age-related macular degeneration by Australian pharmaceutical company Opthea, at eight hospitals, including Kyunghee University Hospital. To evaluate the efficacy and safety of intravitreal administration of 'OPT-302' in combination with 'aflibercept' compared to 'aflibercept' alone, in 69 patients with neovascular age-related macular degeneration...Eight phase 1 trials were also approved this week...Sanofi-Aventis Korea's 'SAR443122...'"

New P1 trial • New P3 trial • Age-related Macular Degeneration • Ophthalmology • Psoriasis

Denali Therapeutics Reports Second Quarter 2021 Financial Results and Business Highlights (GlobeNewswire) - “Under the collaboration agreement, Denali received a milestone payment of $15 million from Sanofi in July 2021 related to the initiation of the Phase 2 study with DNL758….Collaboration revenue was $22.9 million for the three months ended June 30, 2021, compared to $5.8 million for the three months ended June 30, 2020. The increase of $17.1 million in collaboration revenue was primarily due to the achievement of a $15.0 million milestone in June 2021 under our collaboration with Sanofi related to the initiation of the Phase 2 study of DNL758…”

Commercial • Cutaneous Lupus Erythematosus • Immunology • Lupus • Systemic Lupus Erythematosus

Denali Therapeutics Announces Initiation of Phase 2 Study by Partner Sanofi of RIPK1-Inhibitor DNL758 (SAR443122) in Cutaneous Lupus Erythematosus (CLE) Patients (GlobeNewswire) - "Denali Therapeutics...announced that its partner Sanofi has commenced dosing in a Phase 2 study of DNL758 (SAR443122), a peripherally-restricted small molecule inhibitor of RIPK1, in patients with cutaneous lupus erythematosus (CLE)."

Enrollment status • Cutaneous Lupus Erythematosus • Inflammation • Lupus

Proof of concept study of SAR443122 in patients with cutaneous lupus erythematosus A SAR443122 koncepció-igazoló vizsgálata cutan lupus erythematosusban szenvedő betegeknél (clinicaltrialsregister.eu) - P2; N=135; Ongoing; Sponsor: Sanofi-Aventis Recherche & Développement

Clinical • New P2 trial • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Denali Therapeutics Reports First Quarter 2021 Financial Results and Business Highlights (GlobeNewswire) - "Sanofi plans to commence dosing in a Phase 2 study of DNL758 (SAR443122) in CLE patients in the first half of 2021....EIF2B activator (DNL343): Initiate Phase 1b study in ALS patients: 2H 2021; PTV:PGRN (DNL593): File IND application or CTA: Late 2021; ATV:TREM2 (DNL919): File IND application or CTA: Late 2021/Early 2022;"

IND • New P1 trial • New P2 trial • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Lupus

CLEan: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P2; N=88; Recruiting; Sponsor: Sanofi; Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Denali Therapeutics Reports Full Year 2020 Financial Results and Business Highlights (GlobeNewswire) - P1b; N=68; NCT04469621; Sponsor: Sanofi; "In October 2020, Denali reported that Sanofi completed enrollment in a Phase 1b clinical trial of DNL758 (SAR443122)...DNL758 was found to be generally well tolerated and resulted in changes in disease relevant biomarkers and clinical outcome trends consistent with the proof of mechanism. Based on the rapidly evolving landscape of treatment and prevention options for COVID-19, Sanofi has made a sponsor decision to hold further development in COVID-19 at this time."

Biomarker • Discontinued • P1 data • Infectious Disease • Novel Coronavirus Disease