Syros Pharmaceuticals

• Kyoto-based Rege Nephro has acquired Tamibarotene-related clinical and non-clinical assets from Syros Pharmaceuticals to advance its ADPKD treatment program. • Tamibarotene (RN-014), a retinoic acid receptor agonist, is currently in Phase 2 trials in Japan for ADPKD with plans to expand clinical development to the United States. • The acquisition includes human safety data for NDA submission, manufacturing contracts, and drug products, potentially accelerating Rege Nephro's U.S. clinical development timeline.

Biotechnology companies Syros Pharmaceuticals and Cassava Sciences reported disappointing Phase III clinical trial results, leading to significant stock price declines. The setbacks highlight the ongoing challenges in late-stage drug development and the critical importance of clinical trial outcomes for biotech companies.

• The Phase 3 SELECT-MDS-1 trial evaluating tamibarotene plus azacitidine did not meet its primary endpoint of improved complete response (CR) rate in higher-risk myelodysplastic syndrome (HR-MDS) patients. • The CR rate in the tamibarotene arm was 23.8% compared to 18.8% in the placebo arm; however, this difference was not statistically significant (p = 0.2084). • Syros Pharmaceuticals plans to discontinue the trial and review the data, and the trial's failure constitutes an event of default under its loan agreement. • Tamibarotene, an oral RARα agonist, was being investigated in HR-MDS patients with _RARA_ gene overexpression.

• Syros Pharmaceuticals' tamibarotene, combined with azacitidine, did not meet the primary endpoint of complete response (CR) in a Phase III trial for myelodysplastic syndrome (MDS) patients. • The SELECT-MDS-1 trial showed a CR rate of 23.8% in the tamibarotene arm versus 18.8% in the placebo arm, with a non-statistically significant p-value of 0.2084. • Syros is currently analyzing the data to determine the next steps for the development program. • Adaptimmune reported positive results from a pivotal study for its second candidate, lete-cel, with plans for a rolling BLA filing in 2025.

• Syros Pharmaceuticals' stock plummeted after its Phase III SELECT-MDS-1 trial of tamibarotene plus azacitidine failed to meet the primary endpoint in higher-risk myelodysplastic syndrome (HR-MDS) patients. • The trial, involving 190 patients, showed similar complete response rates in both the treatment (23.8%) and placebo (18.8%) groups, leading to the discontinuation of the study. • This setback follows a previous Phase II trial of tamibarotene in acute myeloid leukemia (AML) that was unlikely to meet its primary endpoint, further impacting investor confidence. • The failure of the Phase III trial triggers a default event under Syros' secured loan facility with Oxford Finance, adding financial strain to the company.

• Syros Pharmaceuticals' tamibarotene failed to meet the primary endpoint in the SELECT-MDS-1 Phase III trial for myelodysplastic syndromes (MDS). • The trial's failure dashes hopes that positive signals seen in earlier studies would translate into a viable treatment for MDS patients. • This setback follows a previous negative result for tamibarotene in acute myeloid leukemia, raising concerns about its broader clinical utility. • The company is evaluating the future steps for the drug development program following the disappointing trial outcome.

• Syros Pharmaceuticals' stock plummeted after its Phase III SELECT-MDS-1 trial of tamibarotene plus azacitidine failed to meet the primary endpoint. • The trial focused on newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression. • The complete response rate was similar in both the treatment (23.8%) and placebo groups (18.8%), leading to the study's discontinuation. • This setback follows a prior futility analysis indicating a low probability of success for tamibarotene in acute myeloid leukemia (AML).

• Syros Pharmaceuticals' stock plummeted after its Phase III SELECT-MDS-1 trial of tamibarotene plus azacitidine failed to meet the primary endpoint in higher-risk myelodysplastic syndrome (HR-MDS) patients. • The trial, involving 190 patients with RARA gene overexpression, showed similar complete response rates in both the treatment (23.8%) and placebo (18.8%) groups. • Following the negative results, Syros plans to discontinue the study and reassess its strategic options, while also facing a default event under its loan facility with Oxford Finance. • This setback follows a previous Phase II trial failure of tamibarotene in acute myeloid leukemia (AML), further impacting investor confidence in Syros' lead cancer therapy.

• Syros Pharmaceuticals anticipates pivotal complete response (CR) data from the SELECT-MDS-1 trial of tamibarotene in higher-risk myelodysplastic syndrome (HR-MDS) by mid-November 2024. • The company has strategically realigned to prioritize tamibarotene development and pre-launch activities, discontinuing investment in SY-2101 and other programs. • Financial results for Q3 2024 show reduced operating expenses and net loss compared to the previous year, driven by cost reduction measures and strategic realignment. • Syros is collaborating to develop diagnostic tests for RARA overexpression to identify patients most likely to benefit from tamibarotene treatment.

• Syros Pharmaceuticals remains on track to complete enrollment in the SELECT-MDS-1 trial by Q4 2023 and announce pivotal complete response data in Q3 2024. • The SELECT-MDS-1 trial protocol was amended to include overall survival as a key secondary endpoint, potentially streamlining the path to full approval. • Initial data from the randomized Phase II trial of tamibarotene in AML are expected in Q4 2023, with additional data in 2024.