- Sanofi SA elected to terminate its second amended and restated collaboration and license agreement with Regulus Therapeutics Inc , initially announced in 2014.
- In July 2022, Sanofi decided to terminate the Phase 2 clinical study of lademirsen for Alport syndrome for failure to meet Sanofi’s pre-defined futility criteria.
- Safety issues forced a revamp of that late-stage program when Sanofi flagged a failure for its microRNA drug lademirsen.
- At that time, Sanofi was evaluating other opportunities for the program in other indications. The decision to terminate the study did not stem from any safety issues. The termination will become effective on February 5, 2023.
- Lademirsen was the only product candidate from the collaboration advanced against miR-21 into the clinic.
- In addition, Sanofi had opt-in rights to a preclinical program targeting miR-221/222 for oncology indications.
- Regulus was eligible to receive $25.0 million in further development milestone payments if the Phase 2 study of lademirsen achieved its primary clinical endpoint or upon Sanofi’s election to advance the program into later stages of clinical development.
- In addition, if Sanofi exercised its opt-in rights to the miR221/222 program, Regulus was eligible to receive milestone payments of up to $38.8 million for proof-of-concept option exercise fees, $25.0 million for clinical milestones and up to $130.0 million for regulatory and commercial milestones.
- Day One Biopharmaceuticals announced topline results from the ongoing Phase 2 FIREFLY-1 trial evaluating tovorafenib (DAY101) as a monotherapy in recurrent or progressive pediatric low-grade glioma (pLGG).
- Pediatric low-grade glioma is the most common brain tumor diagnosed in children.
- Additional data will be submitted for presentation at an upcoming medical meeting in the second quarter of 2023.
- Overall response rate (ORR) of 64% and clinical benefit rate (CBR) of 91% were observed in 69 heavily-pretreated, RANO-evaluable patients.
- Based on 77 treated patients, safety data indicated monotherapy tovorafenib to be generally well-tolerated.
- The most common side effects reported related to tovorafenib were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%), and maculopapular rash (42%).
- In addition to FIREFLY-1, Day One is expanding the development of tovorafenib as a front-line therapy for patients newly diagnosed with pLGG.
- The global, Phase 3, registrational FIREFLY-2/LOGGIC clinical trial is evaluating once-weekly monotherapy tovorafenib in newly-diagnosed patients with pLGG harboring a known activating RAF alteration.
