Syros Pharmaceuticals, Inc. Q1 FY2023 earnings call

• Clinical progress in MDS: The SELECT-MDS-1 trial is on track to complete enrollment of 190 patients in the fourth quarter of 2023 and announce pivotal complete response data in the third quarter of 2024. The protocol was amended to include overall survival as a key secondary endpoint while maintaining complete response as the primary endpoint. - AML: Following promising safety lead-in data, the randomized portion of the Phase II trial was initiated last quarter, with initial data expected in the fourth quarter of 2023 and additional data in 2024. - APL: On track to provide an update on the dose confirmation study of 2101 in the second half of 2023, outlining the planned development path and timing for a registration pathway. - Syros believes MDS, AML, and APL represent significant market opportunities in the frontline setting, with potential for commercial efforts in the United States.

In the first quarter of 2023, Syros recognized $3 million in revenue, which consisted entirely of revenue from its collaboration with Pfizer. Comparatively, in the first quarter of 2022, Syros recognized $5.5 million in revenue, with $5.1 million from the Pfizer collaboration and $400,000 from the Incyte collaboration.

• SELECT-MDS-1 trial: Set to complete enrollment of 190 patients in Q4 2023 and report pivotal complete response data in Q3 2024; protocol amended to include overall survival as a secondary endpoint. - AML Phase II trial: Initial data expected in Q4 2023 with additional data in 2024. - 2101: Update on the dose confirmation study expected in the second half of 2023, detailing the development path and registration pathway timing for APL.

Forward-looking statements made during the call are subject to various risks, uncertainties, and other factors, including those set forth in the Risk Factors section of Syros' annual report on Form 10-K and quarterly report on Form 10-Q filed with the SEC, which could cause actual events or results to differ materially from forward-looking statements.

Q: Inquiry about the powering of the overall survival endpoint in the SELECT-MDS-1 trial.

A: David Roth responded that the study is over 90% powered to demonstrate a difference in complete response rates between the arms, and 550 patients provide 80% power to detect a difference in median overall survival between the arms.

Q: Details on the control arm and testing arm assumptions for overall survival in the MDS trial.

A: David Roth noted that the control arm assumption references the 18.6 months median overall survival for azacitidine as a single agent in higher-risk MDS, and while specific statistical assumptions for the testing arm weren't stated, historical data for azacitidine was referenced.

Q: Question about interim analyses in the SELECT-AML trial.

A: David Roth mentioned that initial data for the SELECT-AML trial is expected in the fourth quarter of 2023, but no specific guidance on interim analyses was provided.

Q: Inquiry about gating factors for full vs accelerated approval in MDS based on the complete response endpoint.

A: David Roth explained that the FDA views complete response rate as an appropriate primary efficacy endpoint that could support either full or accelerated approval, with the totality of data informing the regulatory decision-making.

Q: Question about the status of the SY-5609 clinical trial and ASCO presentations.

A: Nancy Simonian stated that there are ASCO posters related to SY-5609, with the trial still enrolling and ASCO presentations expected to showcase supportive data for the drug's potential