Syros Pharmaceuticals, Inc. (NASDAQ:SYRS) is a biopharmaceutical company committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. The company's lead candidate, tamibarotene, is an oral, selective retinoic acid receptor alpha (RARα) agonist that has demonstrated promising results in clinical trials for the treatment of acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS).

Business Overview

Syros is focused on advancing tamibarotene, a selective RARα agonist, as a potential new standard of care for higher-risk MDS and AML patients. The company's clinical development strategy is centered on evaluating tamibarotene in genomically defined subsets of these patient populations, specifically those with overexpression of the RARA gene.

In the ongoing Phase 3 SELECT-MDS-1 trial, Syros is evaluating tamibarotene in combination with azacitidine in newly diagnosed HR-MDS patients with RARA overexpression. The trial's primary endpoint is complete response (CR) rate, which can serve as the basis for accelerated or full approval. Syros expects to report pivotal CR data from the first 190 patients in SELECT-MDS-1 by the middle of the fourth quarter of 2024.

Syros is also advancing tamibarotene in the Phase 2 SELECT-AML-1 trial, which is evaluating the combination of tamibarotene, venetoclax, and azacitidine in newly diagnosed unfit AML patients with RARA overexpression. In a pre-specified analysis of the first 23 evaluable patients, the triplet regimen demonstrated a 100% CR/CRi rate, compared to a 70% CR/CRi rate in the control arm of venetoclax and azacitidine. Syros plans to report additional data from the randomized portion of SELECT-AML-1 at the Society of Hematologic Oncology (SOHO) 2024 Annual Meeting in September 2024.

Financials

For the full year 2023, Syros reported annual revenue of $9.9 million, annual net loss of $164.6 million, annual operating cash flow of -$109.8 million, and annual free cash flow of -$110.0 million.

In the second quarter of 2024, the company did not recognize any revenue, compared to $2.8 million in the prior-year period. Research and development expenses decreased to $22.0 million from $29.6 million in Q2 2023, primarily due to a reduction in external R&D costs and lower headcount-related expenses. General and administrative expenses also declined to $5.5 million from $7.2 million in the year-ago quarter.

Syros reported a net loss of $23.3 million, or $0.59 per share, in Q2 2024, compared to a net loss of $36.3 million, or $1.30 per share, in Q2 2023. As of June 30, 2024, the company had $79.0 million in cash, cash equivalents, and marketable securities, which it believes will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into the third quarter of 2025.

Regulatory Milestones and Market Opportunity

Syros has received Fast Track designations from the FDA for tamibarotene in two key indications: 1) in combination with azacitidine for the treatment of adults with newly diagnosed HR-MDS who are positive for RARA overexpression, and 2) in combination with venetoclax and azacitidine for the treatment of newly diagnosed AML with RARA gene overexpression in adults who are over age 75 and who have comorbidities that preclude the use of intensive induction chemotherapy.

The company believes the market opportunity for tamibarotene is significant, as both HR-MDS and unfit AML represent challenging diseases to treat, with limited potential frontline therapies in late-stage development. Syros estimates that approximately 18,500 patients are diagnosed with HR-MDS in the United States and Europe annually, while approximately 25,000 patients are diagnosed with unfit AML in the same regions. The company expects the total global market for MDS patients of all risk groups to grow to approximately $4.7 billion by 2028, and the overall total global market for all AML patients to reach approximately $7.5 billion by 2028.

Risks and Challenges

Syros faces several risks and challenges in the development and commercialization of tamibarotene. These include the ability to successfully complete its ongoing clinical trials, obtain regulatory approvals, and effectively commercialize the product, if approved. The company also relies on third-party collaborators, such as Qiagen, for the development and commercialization of a companion diagnostic test to identify patients with RARA overexpression, which is critical to the success of tamibarotene.

Additionally, Syros has incurred significant net operating losses since its inception and expects to continue to incur losses for the foreseeable future. As of June 30, 2024, the company had an accumulated deficit of $749.8 million. Syros' ability to achieve and maintain profitability is dependent on the successful development and commercialization of tamibarotene and any future product candidates.

Outlook

Syros is well-positioned for several key milestones in the second half of 2024. In September 2024, the company plans to report additional data from the randomized portion of the SELECT-AML-1 trial, which will include clinical activity and tolerability data from a pre-specified analysis of more than 40 newly diagnosed unfit AML patients with RARA overexpression.

By the middle of the fourth quarter of 2024, Syros expects to report pivotal complete response (CR) data from the first 190 patients enrolled in the Phase 3 SELECT-MDS-1 trial. This data could serve as the basis for accelerated or full approval of tamibarotene in newly diagnosed HR-MDS patients with RARA overexpression.

The company is also preparing for the potential commercial launch of tamibarotene in the United States, where it plans to leverage its own commercial infrastructure to deliver the product to patients. In Europe, Syros intends to seek a licensing or partnership agreement to commercialize tamibarotene.

Conclusion

Syros Pharmaceuticals is poised for a potential breakthrough in the treatment of hematologic malignancies with its lead candidate, tamibarotene. The company's strategic focus on genomically defined patient populations, coupled with the promising clinical data and regulatory milestones, positions tamibarotene as a promising new standard of care for higher-risk MDS and AML patients. With key data readouts expected in the second half of 2024, Syros is well on its way to potentially transforming the treatment landscape for these challenging diseases.