Unmet Needs
Starting with hematologic cancers
Immunomodulatory drugs, including Revlimid® (lenalidomide), are standard treatment options, currently approved for multiple myeloma, mantle cell lymphoma, and other lymphomas. Yet they reflect the same core tension between efficacy and tolerability that characterizes this treatment landscape.
Revlimid remains a foundational standard of care, used broadly in combination regimens across multiple myeloma and lymphoma. However, its toxicity profile drives dose reductions in up to 60%, or discontinuation in up to 30% of patients who cannot complete full courses of therapy or stay on treatment long enough to realize its full benefit.
STAR-LLD is a controlled low-dose formulation of lenalidomide that has demonstrated a significantly improved side effect profile compared to Revlimid. By delivering lenalidomide at a lower dose, STAR-LLD is designed to enable more patients to stay on treatment longer – reducing discontinuations that deprive patients of clinical benefit and potentially improving response rates, progression-free survival, and quality of life.
We believe that STAR-LLD has the potential to replace Revlimid in 1L and 2L, as well as recover patients who have dose reduced or discontinued use in later lines of therapy. STAR-LLD also has the potential to expand Revlimid use by improving outcomes when used in combination in later lines of therapy.
Rationale for STAR-LLD in combination with
T-Cell Engagers and CAR-T Cell therapies
Checkpoint inhibitors, CAR-T therapies, bispecific antibodies, and IMiDs have transformed treatment of hematologic malignancies, yet many patients continue to experience treatment-limiting toxicities, cytokine release syndrome, cytopenias, infections, and discontinuations, as well as immune exhaustion that limits durability of response and contributes to eventual relapse. While remarkable progress has been achieved through molecular engineering, little attention has been directed toward optimizing how these therapies engage the immune system over time.
Applying the principle of Temporal Controlled Pharmacology, Starton’s vision is to enhance the activity of T-Cell Engager (TCE) and CAR-T cell therapies without additional severe toxicities observed with oral Revlimid and CELMoDs. We intend to conduct multiple studies with STAR-LLD in combination with T-cell engager and CAR-T cell therapies, with our initial focus being on lymphoma and multiple myeloma.
Combining lenalidomide with T-cell engagers and CAR-T cell therapies represents a highly synergistic approach to overcome post-infusion relapse and rescue suboptimal immune responses in refractory malignancies. Unlike standard oral Revlimid, which causes toxic 10–20-fold peak serum spikes, Starton’s continuous low-dose administration avoids peak-related toxicities while maintaining steady therapeutic immune modulation. This exposure ensures uninterrupted T-cell proliferation and NK-cell surveillance without causing immune exhaustion by avoiding increases in immune markers like Tregs, PD-1, LAG-3, and TIM-3.