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Immunomedics Offers Clinical Updates on Subcutaneous Injections of Veltuzumab

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Immunomedics, Inc. (Nasdaq: IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today announced that subcutaneous administration of veltuzumab, as a single agent, demonstrated promising activity in patients with relapsed immune thrombocytopenia (ITP), even in more heavily treated patients with the chronic disease, and in patients with chronic lymphocytic leukemia (CLL).

Veltuzumab is a second generation humanized anti-CD20 antibody constructed using the same human donor frameworks as epratuzumab, the Company's humanized anti-CD22 antibody. The complementarity-determining regions (CDRs) of veltuzumab are identical to rituximab, except for one amino acid residue, which appears to give veltuzumab some unique properties. In an animal model of human lymphoma, veltuzumab demonstrated higher efficacy than rituximab, and in cell culture experiments, this humanized antibody showed slower off-rates and increased complement-dependent cytotoxicity compared to rituximab.

In a published study, veltuzumab reversed life threatening anemia and thrombocytopenia in a patient with systemic lupus erythematosus who was unresponsive to rituximab. In non-Hodgkin lymphoma (NHL) patients who had received prior therapies, 4 once-weekly infusions of veltuzumab produced a complete response rate of 25% in a study of 84 patients, even at the low dose of 80 mg/m^2 given intravenously.

A subcutaneous formulation with a high concentration of veltuzumab was developed to avoid the need for lengthy intravenous administration and dedicated infusion suites. Published results show this formulation, which can be administered within a few seconds due to the low injection volume, to be active in patients with NHL. (For more information, please refer to the Company's 2011 publication by Negrea et al. in Haematologica, volume 96, pages 567-73).

In the presentation given at this ASH meeting, two subcutaneous dosing cohorts were evaluated in a Phase I/II study in relapsed ITP. The first cohort of 34 patients received 2 veltuzumab doses at 80, 160 or 320 mg administered 2 weeks apart for a total dose of 160, 320 or 640 mg, respectively. The second cohort is enrolling patients to receive veltuzumab at 320 mg per dose given once-weekly for 4 weeks for a total dose of 1280 mg. Thus, four different doses are being evaluated.

At the time of reporting, 10 patients were enrolled into the second cohort, with 1 patient rolled over from the first cohort. Among the 44 patients enrolled, 42 were evaluable for efficacy. The overall objective response (OR) rate was 50%, with 12 patients (29%) having a complete response (CR), which means that their platelet levels rose to or above 100,000 per µL.

For the 12 patients with ITP one year or less, OR and CR rates were 58% and 25%, respectively. For the 30 patients who had the more refractory, chronic disease, of which 50% had the disease between 5 to 37 years, 47% still achieved ORs, including 30% CRs. Responses occurred across all doses tested, including the lowest dose at 80 mg x 2.

Response durability from initial dose was available from patients in the first cohort only. Of the 17 patients who responded to subcutaneous veltuzumab, the median relapsed-free survival was 8 months, with 47% of responders maintaining their response longer than 1 year. Seven responding patients had been retreated, with 2 patients (29%) achieving responses comparable to their initial responses.

This multicenter study was presented by Howard A. Liebman, MD, of the Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, CA, and included also Georgia Cancer Specialists, Marietta, GA; Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NJ; and Low Country Cancer Care Associates, Savannah, GA.

In oncology, the Company has previously reported that 4 subcutaneous injections of low-dose veltuzumab given 2 weeks apart produced responses in 17 NHL patients that are comparable to intravenous doses.

For CLL, however, high levels of circulating leukemic cells may require more frequent and prolonged dosing. Thus, a multicenter, open-label, Phase I study of single-agent veltuzumab therapy was undertaken to evaluate 2 different subcutaneous dosing schedules. Over an 8-week treatment period, three dose levels of veltuzumab at 80, 160, or 320 mg were either injected once every 2 weeks for a total of 4 doses (cohort 1), or given twice weekly for a total of 16 doses (cohort 2). A total of 11 patients with newly diagnosed or relapsed CLL had been enrolled into the first cohort, with cohort 2 currently having 10 patients enrolled.

Results from 18 assessable patients were presented by Matt E. Kalaycio, MD, of Cleveland Clinic's Taussig Cancer Institute, Cleveland, OH. Other research sites included Low Country Cancer Care Associates in Savannah, GA; Weill Cornell Medical College in New York, NY; and the Carol G. Simon Cancer Center, Morristown, NJ. The overall disease control rate was 83%, with 12 patients having stable disease (SD) and 3 patients (17%) reporting a partial response as their best responses. Four SD patients had relapse-free survival for 6 – 12 months and all 3 partial responders were relapse-free at 6, 12 and 24 months. Despite cumulative doses ranging from 320 to 5120 mg, similar disease control rates were observed across all 3 dose levels (80 vs. 160 vs. 320 mg) and dosing schedules (cohort 1 vs. 2).

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