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

A Randomized Phase I Trial Evaluating Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eclitasertib, a RIPK1 Inhibitor, in Healthy Participants. (PubMed, Adv Ther) - "Single and repeated doses of eclitasertib were well tolerated in healthy participants and potently inhibited RIPK1 activation."

Journal • P1 data • PK/PD data • CNS Disorders • Inflammation • Pain • RIPK1

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