Clinical, preclinical results of ISF35 in CLL patients presented at ASH 2010

Dec 10 2010

Memgen, LLC announced the presentation of clinical and preclinical results for its lead product, ISF35, during the 52nd Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida.  The research and clinical development of ISF35 announced today was led by Januario Castro, MD, and Thomas Kipps, MD, PhD, both at the University of California, San Diego (UCSD).

“This clinical and preclinical research lays the groundwork for expanded studies evaluating ISF35 in combination with chemotherapy”

A poster presentation (Abstract 1472), entitled Ad-ISF35-Transduced Autologous Cells Promote In Vitro and In Vivo Chemosensitization to FCR and Durable Complete Responses In Patients with Del(17p) / P53 Defective Chronic Lymphocytic Leukemia, described results from a Phase Ib clinical trial co-sponsored by the Leukemia & Lymphoma Society.  The clinical study is evaluating the safety and efficacy of ISF35 in combination with chemotherapy in patients with fludarabine-refractory and/or 17p-deleted CLL. 

Patients in this study received their own tumor cells modified to express ISF35.  Following ISF35 cell therapy, subjects received monthly courses of FCR, a standard chemotherapy regimen.  Dr. Castro's data show three of four patients in the study responded, including two durable complete responses which continue to date with a median follow-up of 18 months.

A second poster presentation (Abstract 1476), entitled Immune Gene Therapy for Patients with CLL Using Repeat Dose Intranodal Injection of Ad-ISF35, a Replication Incompetent Vector Expressing a Membrane-Stable CD40 Binding Protein, highlighted results from an ongoing Phase II clinical trial evaluating multiple direct intranodal injections of Ad-ISF35 in patients with high-risk, progressive CLL. Most patients experienced reductions of 50% or greater in three response parameters:  leukemia cell counts, swollen lymph nodes, and enlarged spleen.  The findings suggest that multiple direct injections of ISF35 are feasible, have a favorable safety profile consisting mostly of flu-like symptoms, and induce systemic biological responses and apoptosis in cancer cells.

A third poster presentation (Abstract 1470), entitled Ad-ISF35 Intratumoral Administration Induces a Bystander Effect and Immune-Mediated Tumor Rejection with a Safe Vector Biodistribution and Toxicology Profile In a NHL Mouse Model,  described results from a preclinical study showing that Ad-ISF35 injected directly into the tumors of mice bearing subcutaneous NHL breaks tumor tolerance and induced complete tumor regression and immunity to tumor rechallenge. 

"This clinical and preclinical research lays the groundwork for expanded studies evaluating ISF35 in combination with chemotherapy," said Mark Cantwell, PhD, Memgen's VP of Research & Development and co-inventor of ISF35.  "Not only does this approach show promise in refractory CLL, which has an urgent medical need, but the results of direct injection of ISF35 for CLL suggest a broad applicability of ISF35 for many hematologic and solid tumor indications."