Immunomedics Announces Antitumor Effect of Sacituzumab Govitecan (IMMU-132) in Triple-Negative Breast Cancer Can be Enhanced With DNA-Repair Inhibitors

MORRIS PLAINS, N.J., Jan. 09, 2017 (GLOBE NEWSWIRE) -- Immunomedics, Inc. (NASDAQ:IMMU) today announced that, based on a preclinical study, the encouraging efficacy observed with sacituzumab govitecan (IMMU-132) in patients with metastatic triple-negative breast cancer (TNBC) has the potential to be improved further when combined with agents that inhibit DNA repair pathways both in patients with mutated and wild-type BRCA1/2. Results from this preclinical study were published online in Clinical Cancer Research¹, which is a major peer-reviewed journal in cancer research and the official publication of the American Association for Cancer Research (AACR).

“This preclinical study is part of our ongoing strategy to broaden the applicability of this important asset for the treatment of patients with solid cancers and the positive results we have achieved thus far are a testament to the strength of our talented team. The progress we have made affirms our commitment to continued product development and near-term value creation for our patients and stockholders,” remarked Cynthia L. Sullivan, President and Chief Executive Officer.

IMMU-132 is a first-in-class antibody-drug conjugate (ADC) developed by the Company by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high drug-to-antibody ratio to a humanized antibody that targets the Trop-2 receptor expressed by many solid cancers. In a single-arm Phase 2 study, this ADC has produced rapid and durable responses in metastatic TNBC patients, with only limited and manageable Grade 3 or 4 toxicity, and has received a Breakthrough Therapy Designation from the FDA in this cancer setting.

SN-38 is the active metabolite of irinotecan (Camptosar), which is used to treat certain solid cancers as a part of combination therapies. It exerts its cell-killing activity by inhibiting topoisomerase I, an enzyme needed by the cell for normal DNA replication. This inhibition results in breaks in the DNA during replication, leading ultimately to the cell’s death if left unrepaired by the cell. The goal of this preclinical study was to determine whether the DNA-damaging property of IMMU-132 can be augmented by agents that inhibit the repair of DNA.

Poly (adenosine diphosphoribose) polymerase (PARP) is a family of enzymes whose primary function is to repair DNA breaks. It is one of several proteins used by cells for this purpose.  PARP inhibitors (PARPi), such as olaparib and talazoparib, are currently under investigation in cancers with existing DNA-repair defects; namely, BRCA1/2. BRCA1/2 are a pair of genes (BRCA1 and BRCA2) that encode proteins important in a cell’s ability to repair double-stranded DNA breaks. In cell culture, the cytotoxicity of IMMU-132 when combined with one of three different PARPi’s (olaparib, talazoparib, and rucaparib) produced synergistic growth inhibition in BRCA1/2-defective human TNBC tumor lines. Furthermore, combining IMMU-132 with these PARPi’s also demonstrated synergy in BRCA1/2 wild-type tumor lines in which the DNA-repair pathways are not defective. In mice bearing human TNBC tumors with mutated BRCA1/2, a combination of IMMU-132 plus olaparib or talazoparib produced significantly improved antitumor effects and delay in time-to-tumor-progression, compared to monotherapy. Most importantly, in mice bearing tumors that are not defective in DNA repair (BRCA1/2 wild-type), the combination of IMMU-132 plus olaparib imparted a significant antitumor effect and survival benefit above that achieved with monotherapy. Noteworthy, this combination was well tolerated, with no substantial changes in hematologic parameters.

“These preclinical results indicate that the combination of PARPi and IMMU-132 could broaden the range of tumors that are usually treated with the former to a TNBC patient population that includes BRCA1/2 wild-type tumors. Given the promising results obtained thus far with IMMU-132 in patients with TNBC, the logical next step is to combine this therapy with PARPi to further improve clinical outcome,” Ms. Sullivan added. 

Improved efficacy of IMMU-132 when combined with olaparib or talazoparib in mice bearing TNBC tumors that are deficient in DNA repair

N = Number of mice per group
N.A. = Not Applicable

In addition to publishing these encouraging preclinical results in TNBC, Immunomedics is also focused on achieving a number of critical milestones in the near-term including:

• Preparing to submit a Biological License Application (BLA) to the FDA for accelerated approval for IMMU-132 for patients with metastatic TNBC in mid-2017;
• Publishing Phase 2 study results with IMMU-132 in TNBC in a peer-reviewed medical journal;
• Presenting interim results of Phase 2 clinical trials of IMMU-132 for patients with urinary bladder cancer at the ASCO symposium on genitourinary cancers to be held in February 2017;
• Continuing preclinical development of the new ADC, IMMU-140, as a therapeutic for five different blood cancers (non-Hodgkin lymphoma, chronic lymphocytic leukemia, acute lymphocytic leukemia, acute myeloid leukemia, and multiple myeloma); poster presented at 2016 meeting of American Society of Hematology (ASH);
• Pursuing licensing and other strategic activities with regard to IMMU-132 and other clinical and preclinical pipeline drug development candidates, as well as platform technologies, with the support of Greenhill & Co. as its financial advisor;
• Initiation of a Phase 3 confirmatory trial in TNBC during early 2017;
• Potential for Breakthrough Therapy Designation in small-cell and non-small-cell lung, and urinary bladder cancers; and
• Once IMMU-132 is partnered, the Company could then advance many other preclinical assets into clinical development and even other licensing arrangements; licensing discussions involving some of these other assets are in fact ongoing.

Reference

1. Cardillo TM, Sharkey RM, Rossi DL, et al. Synthetic lethality exploitation by an anti-Trop-2-SN-38 antibody-drug conjugate, IMMU-132, plus PARP-inhibitors in BRCA1/2-wild-type triple-negative breast cancer. Clin Cancer Res. Epub ahead of print. January 2017.

About Immunomedics
Immunomedics is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, autoimmune disorders and other serious diseases. Immunomedics’ advanced proprietary technologies allow the Company to create humanized antibodies that can be used either alone in unlabeled or “naked” form, or conjugated with radioactive isotopes, chemotherapeutics, cytokines or toxins. Using these technologies, Immunomedics has built a pipeline of eight clinical-stage product candidates. Immunomedics’ portfolio of investigational products includes antibody-drug conjugates (ADCs) that are designed to deliver a specific payload of a chemotherapeutic directly to the tumor while reducing overall toxic effects that are usually found with conventional administration of these chemotherapeutic agents. Immunomedics’ most advanced ADCs are sacituzumab govitecan (IMMU-132) and labetuzumab govitecan (IMMU-130), which are in Phase 2 trials for a number of solid tumors and metastatic colorectal cancer, respectively. IMMU-132 has received Breakthrough Therapy Designation from the FDA for the treatment of patients with triple-negative breast cancer who have failed at least two prior therapies for metastatic disease. Immunomedics has a research collaboration with Bayer to study epratuzumab as a thorium-227-labeled antibody. Immunomedics has other ongoing collaborations in oncology with independent cancer study groups. The IntreALL Inter-European study group is conducting a large, randomized Phase 3 trial combining epratuzumab with chemotherapy in children with relapsed acute lymphoblastic leukemia at clinical sites in Australia, Europe, and Israel. Immunomedics also has a number of other product candidates that target solid tumors and hematologic malignancies, as well as other diseases, in various stages of clinical and preclinical development. These include combination therapies involving its antibody-drug conjugates, bispecific antibodies targeting cancers and infectious diseases as T-cell redirecting immunotherapies, as well as bispecific antibodies for next-generation cancer and autoimmune disease therapies, created using its patented DOCK-AND-LOCK® protein conjugation technology. The Company believes that its portfolio of intellectual property, which includes approximately 304 active patents in the United States and more than 400 foreign patents, protects its product candidates and technologies. For additional information on the Company, please visit its website at www.immunomedics.com. The information on its website does not, however, form a part of this press release.

This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials (including the funding therefor, anticipated patient enrollment, trial outcomes, timing or associated costs), regulatory applications and related timelines, out-licensing arrangements (including the timing and amount of contingent payments), forecasts of future operating results, potential collaborations, and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, the Company’s dependence on business collaborations or availability of required financing from capital markets, or other sources on acceptable terms, if at all, in order to further develop our products and finance our operations, new product development (including clinical trials outcome and regulatory requirements/actions), the risk that we or any of our collaborators may be unable to secure regulatory approval of and market our drug candidates, risks associated with the outcome of pending litigation and competitive risks to marketed products, and the Company’s ability to repay its outstanding indebtedness, if and when required, as well as the risks discussed in the Company’s filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.