Syros Pharmaceuticals, Inc. Q4 FY2023 earnings call

• Late last year, initial data from the SELECT-AML-1 trial was announced.
• Completed an equity financing of approximately $45 million in late 2023.
• 2024 is a critical year with expected pivotal data from the SELECT-MDS-1 trial and additional randomized data from the SELECT-AML-1 trial.
• The SELECT-MDS-1 Phase 3 trial completed enrollment of 190 patients for primary endpoint analysis and is on track to report pivotal CR data by mid-2024 Q4.
• Tamibarotene has the potential to be a transformational new standard of care for frontline treatment of hematologic malignancies.
• SELECT-AML-1 Phase 2 trial initial data showed 100% CR-CRI rate in the triplet regimen vs 70% in the doublet, rapid time to response, and favorable safety profile.
• The SELECT-MDS-1 Phase 3 trial is a randomized double-blind placebo control evaluating tamibarotene + azacitidine vs placebo + azacitidine in higher-risk MDS patients with RARA overexpression.

Revenues for the fourth quarter of 2023 were $400,000, and for the full year 2023 were $9.9 million. In the fourth quarter of 2022, revenues were negative $800,000, and for the full year 2022 were $14.9 million. R&D expenses for the fourth quarter of 2023 were $21.5 million, and for the full year 2023 were $108.2 million. In the fourth quarter of 2022, R&D expenses were $27.9 million, and for the full year 2022 were $111.9 million. G&A expenses for the fourth quarter of 2023 were $5.9 million, and for the full year 2023 were $28.3 million. In the fourth quarter of 2022, G&A expenses were $7.3 million, and for the full year 2022 were $29.3 million. Net loss for the fourth quarter of 2023 was $64.4 million or $2.18 per share, and for the full year 2023 was $164.6 million or $5.81 per share. Cash and cash equivalents as of December 31, 2023 were $139.5 million, compared to $202.3 million at the end of 2022.

• Current cash position is sufficient to fund operating expenses and capital expenditures into Q2 2025.
• Anticipates pivotal data from the SELECT-MDS-1 trial in mid-2024 Q4.
• Plan to launch tamibarotene in the US with its own specialty sales force and has made progress on the launch plan.

• Forward-looking statements are subject to risks and uncertainties outlined in the annual report on Form 10-K and future SEC filings. Actual events or results may differ materially from forward-looking statements.

Q: Can you discuss on the complete response endpoint, regulatory discussions about how it could support an FDA filing and how does duration of response factor into regulatory authorities' evaluation of the CR data?

A: David Roth states that CR is a clinically meaningful endpoint associated with hematologic improvement. Discussions with the FDA have confirmed CR can support a regulatory decision for full or accelerated approval, and the durability of remission is considered.

Q: In other trials in MDS or AML, the bar for duration of response seems to be somewhere in the five to six month range. Is that a reasonable expectation in MDS and SELECT-MDS-1 as well? Or are there other data points that we should be considering?

A: David Roth says the duration of response is assessed with the total data package. A meaningful duration is one that lasts over time providing benefit to the patient, and the agency will consider duration, time to response, quality of response, and safety.

Q: Can you talk about some of the medical affairs work and commercial prep that you are starting to do, both for MDS and AML and just what your focus will be, for the rest of 2024?

A: David Roth mentions focus on key opinion leader engagement and educating physicians on RARA overexpression and tamibarotene. Conley Chee adds on launch prep including infrastructure investment and laying the path for launch with education and awareness of tamibarotene.