Schrödinger, Inc. announced that the U.S. Food and Drug Administration has granted Fast Track designation to SGR-1505, the company's clinical-stage MALT1 inhibitor, for treating adult patients with Waldenström macroglobulinemia who have failed at least two lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor.
The designation underscores the significant unmet medical need in this patient population, where treatment failure and disease progression due to BTK resistance continues to challenge clinicians treating hematologic malignancies.
Addressing BTK Resistance Challenges
"Despite the continued therapeutic advances in the treatment of hematologic malignancies, treatment failure and disease progression due to BTK resistance remains a challenge for a growing number of patients," said Karen Akinsanya, Ph.D., president, head of therapeutics R&D and chief strategy officer, partnerships at Schrödinger. "This unmet need represents an opportunity for novel mechanisms such as MALT1 as monotherapy and as part of new combination regimens."
The FDA Fast Track program facilitates development and expedites review of drug candidates treating serious conditions with unmet medical needs. Fast Track designation provides multiple benefits, including more frequent FDA meetings and written communications, plus eligibility for Accelerated Approval, Priority Review, or Rolling Review if relevant criteria are met.
Encouraging Phase 1 Clinical Data
SGR-1505 is currently being evaluated in a Phase 1 clinical study (NCT05544019) for patients with relapsed/refractory B-cell malignancies. Initial data recently presented at the European Hematology Association Annual Congress and International Conference on Malignant Lymphoma demonstrated that SGR-1505 has a favorable safety profile and is well tolerated.
Encouraging signs of preliminary efficacy were observed across multiple B-cell malignancy subtypes, including in Waldenström macroglobulinemia patients previously treated with a BTK inhibitor prior to starting SGR-1505.
"We believe this Fast Track designation in Waldenström macroglobulinemia, combined with our encouraging Phase 1 data across a broad range of relapsed/refractory B-cell malignancies such as chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and marginal zone lymphoma, reinforce the potential of SGR-1505 as a future therapeutic option for patients," said Margaret Dugan, chief medical officer at Schrödinger.
Novel MALT1 Mechanism of Action
SGR-1505 is an oral investigational MALT1 inhibitor targeting a protein that plays a central role in key signaling pathways driving cancer cell survival and proliferation. MALT1's location downstream of BTK in the NF-κB signaling pathway makes it an attractive target for developing novel therapeutics for a potentially broad range of B-cell malignancies.
In preclinical studies, SGR-1505 demonstrated high potency and selectivity, showing anti-tumor activity in preclinical models both as monotherapy and in combination with BTK and BCL-2 inhibitors. Emerging therapeutic rationale also supports MALT1 inhibition as a potential treatment for inflammatory and autoimmune disorders.
Computational Drug Discovery Success
SGR-1505 was designed using Schrödinger's computational platform and discovered approximately 10 months after the company initiated its MALT1 program. The drug previously received FDA orphan drug designation for Mantle Cell Lymphoma on August 11, 2023, based on preclinical data.
The company plans to discuss Phase 1 study results and recommended Phase 2 dose with the FDA later this year, potentially advancing toward pivotal trials in this underserved patient population.
