RARE Daily

Syros Acquires Clinical Candidate for the Treatment of Rare Blood Cancer from Orsenix

December 7, 2020

Rare Daily Staff

Syros Pharmaceuticals has acquired Orsenix’ ORH-2014, a targeted clinical-stage drug candidate that has the potential to dramatically reduce the treatment burden of a standard-of-care regimen for newly diagnosed acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a well-defined subset of acute myeloid leukemia (AML) caused by the formation of an abnormal fusion gene, PML/RARA. This fusion gene leads to the overproduction of immature white blood cells called promyelocytes and the underproduction of healthy blood cells. Signs, symptoms and complications of APL include abnormal bleeding and bruising, anemia, fatigue, and increased risk of infection. APL makes up about 10 percent of AML cases, with an annual incidence of approximately 2,000 patients in the United States and Europe.

Rebranded as SY-2101, ORH-2104 is a novel oral form of arsenic trioxide (ATO). An intravenously administered formulation of ATO is approved for use in combination with All-Trans-Retinoic-Acid (ATRA) in newly diagnosed APL and, while curative in approximately 80-90 percent of patients, its administration requires up to 140 two- to four-hour infusions over the typical course of induction and consolidation treatment.

Because SY-2101 is dosed orally once daily, it has the potential to become the standard-of-care frontline therapy for APL by providing comparable efficacy with a substantially more convenient option that reduces the treatment burden on patients, improving access, and lowering costs to the healthcare system. In a phase 1 clinical trial, led by investigators at the M.D. Anderson Cancer Center, SY-2101 demonstrated bioavailability, pharmacokinetic exposures similar to IV ATO, and a generally well-tolerated safety profile.

Under the terms of the asset purchase agreement, Syros has paid Orsenix $12 million upfront to acquire all assets related to the development and commercialization of SY-2101, including intellectual property, clinical and preclinical data, the regulatory dossier, and product inventory. In addition, Orsenix is eligible to receive a $6 million regulatory milestone related to the development of SY-2101 in APL and commercial milestones of up to $10 million. Orsenix is also eligible to receive single-digit million milestone payments related to the development of SY-2101 in indications other than APL.

“It’s rare to talk about cures in cancer,” said Nancy Simonian, CEO of Syros. “The IV formulation of ATO is part of a treatment regimen that cures most APL patients, but it is extremely burdensome with lengthy infusions over a nearly yearlong course of treatment. We believe an oral form that offers similar efficacy while dramatically reducing the treatment burden on these patients could quickly become a new standard-of-care.”

In conjunction with the asset purchase, Syros raised $90.5 Million in a private placement led by Bain Capital Life Sciences, which extends its cash runway into the second half of 2022.

Syros plans to initiate a dose confirmation study of SY-2101 in the second half of 2021. Following confirmation of a dose that demonstrates comparable PK to IV ATO, Syros intends to initiate a registration-enabling Phase 3 trial in patients with newly diagnosed APL in 2022. Based on interactions between Orsenix and the U.S. Food and Drug Administration, Syros believes molecular complete response rate and event-free survival in comparison to historical control data with IV ATO would support accelerated and full approval, respectively. If successful, Syros believes it could file a New Drug Application with the FDA in 2024.

SY-2101 has orphan drug designation in the United States for the treatment of APL and in Europe for the treatment of AML.

Photo: Nancy Simonian, CEO of Syros

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