New Data on Mentrik Biotech’s Ocaratuzumab (AME-133v) Published in Clinical Cancer Research

Ocaratuzumab, currently in clinical development for hematologic malignancies, is a humanized monoclonal antibody engineered to have increased affinity for CD20 and mediate antibody-dependent cell-mediate cytotoxicity (ADCC) with greater potency than rituximab. In a multi-center Phase I clinical trial, 23 patients with relapsed follicular lymphoma were administered intravenous ocaratuzumab weekly for four doses. Patients were assigned to one of five dose-escalation cohorts of ocaratuzumab, 2, 7.5, 30, 100, or 375 mg/m2. Additionally, all patients enrolled on study had the low-affinity FcγRIIIa polymorphism (SNP coding for F/F or F/V at position 158; F-carriers), who historically have demonstrated poorer response to rituximab treatment (Weng, WK and Levy, R., J Clin Oncol, 2003; Cartron, et al., Blood, 2002).

Ocaratuzumab was well tolerated at all doses. Patients treated at doses as low as 7.5 mg/m2 showed rapid and sustained B-cell depletion, demonstrating that ocaratuzumab is effective at doses significantly lower than that of competing drugs. Within 24 hours of the first infusion, all patients had depletion of circulating B-cells; ninety-six percent of patients had less than 10 x 103 cells/μL. Sustained B-cell depletion lasted for at least eight months following the last infusion in 63% of patients, and up to 18 months in some patients.

Ocaratuzumab is engineered to have 13 to 20 fold greater binding affinity for CD20 and 6 fold greater ADCC than rituximab. Cell binding assays show ocaratuzumab and rituximab competing for an overlapping epitope on the CD20 antigen, with ocaratuzumab inhibiting binding of biotinylated rituximab to CD20 in a concentration-dependent manner.

Phase I/II ocaratuzumab trials in relapsed follicular lymphoma have been conducted in the US and Japan, and a Phase I trial was conducted in US rheumatoid arthritis patients. Many patients relapse following currently available treatments for follicular lymphoma and a significant need for new effective treatment exists, particularly for patients with low-affinity FcγRIIIa allotypes. In Phase I/II trials, ocaratuzumab demonstrated clinical benefit in low-affinity FcγRIIIa patients. Additional development of ocaratuzumab in other oncology and rheumatology indications is being pursued. Subcutaneous formulation for improved patient convenience is also in development.
The recent publication (A Phase I Study of AME-133v (LY2469298) an Fc-Engineered Humanized Monoclonal Antibody in FcγRIIIa-Genotyed Patients with Previously Treated Follicular Lymphoma. Andres Forero-Torres, et al. Clin Cancer Res 5 Jan 2012.) is available at http://clincancerres.aacrjournals.org/.

About Mentrik Biotech

Mentrik Biotech, LLC is a private biopharmaceutical company headquartered in Dallas, TX. The goal of Mentrik Biotech is to optimize oncology-based therapeutics to treat patients with significant unmet medical needs. The company aims to develop convenient, potent, and cost-effective anti-cancer molecules to enhance treatment options for patients and fulfill unmet therapeutic needs. For more information, visit www.mentrik.com.

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