THE PROBLEM

Despite advances in classical Hodgkin’s Lymphoma (cHL) treatment, significant challenges persist with up to 40% of patients relapsing after first-line therapy and 50% after autologous stem cell transplant (aSCT). Current therapies like brentuximab vedotin and checkpoint inhibitors provide sustained remissions in fewer than 25% of r/r patients. Previous CD30-targeting CAR-T approaches showed high response rates but poor persistence due to soluble CD30 binding and host rejection of murine components. There’s an urgent need to address the persistence problem.

THE SOLUTION

OSU-185 addresses these challenges through two key innovations: (1) proximal epitope targeting: specifically binding the membrane-bound region (epitope 2A, amino acids 107-153) that remains after shedding, preventing neutralization by circulating soluble CD30; and (2) optimal humanization: using machine learning and iterative optimization to achieve 91% homology to the murine T105 clone while significantly increasing humanness scores. (A recent study using a non-humanized construct showed that proximal epitope targeting may enhance CD30-targeting CAR-Ts in patients with refractory HL.)

APPLICATIONS

• R/R classic Hodgkin's lymphoma therapy: First-line cellular therapy for patients failing standard treatments, including aSCT
• CD30+ non-Hodgkin's lymphomas therapy: Application in anaplastic large cell lymphoma and other CD30+ NHL subtypes
• Combination therapy with ICB; abrogates need for allo transplant

ADVANTAGES

• Superior target engagement: Binding to membrane-bound CD30 epitope unaffected by soluble CD30 shedding, preventing neutralization
• Reduced immunogenicity: First-in-class humanized scFv design minimizes anti-CAR immune responses
• Enhanced tumor specificity: Demonstrates superior discrimination between CD30+ tumor cells and CD30- healthy tissues in preclinical models

Seeking opportunities for out-licensing and collaboration