Immunomedics Reports Initial Results of a Phase I First-In-Man Study With IMMU-114 in Hematologic Malignancies; 50% Of Patients Show Objective Evidence Of Treatment Activity

Immunomedics, Inc.

today announced that 50% of patients showed objective evidence of treatment activity, including one patient with a complete response, in a Phase 1, first-in-man clinical study of the Company's proprietary humanized antibody, IMMU-114, in patients with relapsed non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). IMMU-114, the newest antibody from the Company to enter clinical trials, targets a human leukocyte transplantation antigen, or HLA-DR, which is a receptor located on the cell surface and whose role is to present foreign antigens to the immune system for the purpose of eliciting an immune response. HLA-DR is expressed by a large number of blood cancers at significantly higher levels than typical B-cell markers, including CD20, thus making it a prime target for antibody therapy. By targeting HLA-DR, a receptor that is different from CD20, CD22, CD30, and CD52 antigens inhibited by other antibodies in lymphoma and leukemia therapy, IMMU-114 may represent a new treatment option to combat these cancers. The anti-HLA-DR antibody is being evaluated as a subcutaneous monotherapy in the dose-escalation study. First results from this study were presented at the 2015 Annual Meeting of the American Society of Hematology by Dr. Deborah M Stephens at the Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. Seventeen patients with a median of 2 prior therapies (range 1 – 7) had been enrolled. All 17 patients had failed rituximab or other anti-CD20 antibody therapies. Ten patients in the initial dose-escalation phase of the study received 200 mg IMMU-114 injections once, twice, or thrice weekly for the first 3 weeks of a 4-week cycle. All patients receive 2 consecutive treatment cycles, followed 4 weeks later by elective maintenance therapy. While the maximum tolerated dose was not determined, with lack of toxicity and preliminary efficacy already observed at the two lowest dose levels, the twice-weekly dosing schedule was chosen for subsequent patients enrolled. Treatment response was assessed using 2007 IWG-NHL or 2008 IW-CLL criteria 4 weeks after cycle 2, then every 3 months until disease progression. At the time of analysis, ten patients were evaluable for treatment response. Best responses from these patients are summarized below: Best Response Dose and Dosing Frequency Number of Patients Complete Response Partial Response Stable Disease Disease Progression 200 mg once-weekly 3 -- -- 1 2 200 mg twice-weekly 6 1 3 -- 2 200 mg thrice-weekly 1 -- -- -- 1 In total, five assessable patients had evidence of treatment response (stable disease, partial and complete responses), including one patient with follicular lymphoma who reported a complete response and another with stable disease, as well as two patients with diffuse large B-cell lymphoma with partial responses and one patient with CLL having a partial response. "Even though the number of patients is small, the fact that most of them had previously failed combination therapies that included rituximab is very encouraging to us," commented Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics. "We are working now to expand this study to also include other hematological cancers." Designed specifically to avoid the severe intravenous infusion reactions seen with earlier anti-HLA-DR antibodies which were IgG1 subtypes, IMMU-114 was created as an IgG4, a subclass of immunoglobulin that does not function by the usual effector-cell activities of antibodies, such as complement-dependent cytotoxicity, or CDC, and antibody-dependent cellular cytotoxicity, or ADCC. As a result, IMMU-114 does not rely on an intact immune system in the patient to kill tumor cells, but directly affects the signaling, metabolism and proliferation of the targeted cancer cells. Since ADCC and CDC are believed to play a major role in causing the side effects of antibody therapy, IMMU-114 is expected to be less toxic to patients. Indeed, subcutaneous injections of IMMU-114 were well tolerated by patients, with only local skin reactions at the injection sites, which were all mild to moderate and transient. Furthermore, only one patient had evidence of immunogenicity of uncertain significance and no other cytopenias or changes in routine safety laboratory results occurred. The presentation also included initial preclinical results showing how IMMU-114 could potentially improve the results of other agents used in the therapy of patients with CLL. Cell culture experiments with a CLL line showed that combining IMMU-114 with a Bruton kinase inhibitor, such as ibrutinib, or a PI3k inhibitor, such as idelalisib, could results in additive therapeutic effects. "Since IMMU-114 so far has not shown any limiting side effects, we believe it could be combined with other agents that are effective in CLL therapy, possibly improving responses without increasing toxicity," Ms. Sullivan also remarked. In addition to Dr. Stephens, other Principal Investigators who participated in this multicenter study are Dr. Alexander N. Starodub, Indiana University Health Center for Cancer Care, Goshen, IN; and Drs. John C Byrd and Beth A. Christian, Comprehensive Cancer Center, The Ohio State University, Columbus, OH.