On January 18, 2017 Immunomedics reported additional value-creation inflection points in its robust pipeline in connection with the Company’s Investor R&D Day held at The Roosevelt Hotel in New York City (Filing, 8-K, Immunomedics, JAN 18, 2017, View Source [SID1234517459]). In addition to announcing new data for sacituzumab govitecan (IMMU-132), Immunomedics detailed the preclinical and clinical progress it has achieved in advancing IMMU-114, IMMU130, IMMU-140 and its immune-oncology program, which the Company believes will result in near- and long-term value creation for stockholders.

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"While IMMU-132 is the key near-term driver of value creation for Immunomedics stockholders, we are making significant progress in advancing the rest of our robust pipeline with the goal of sustained value creation," said Cynthia L. Sullivan, President and Chief Executive Officer. "We are on track to achieve numerous other milestones to position these assets for future monetization in parallel with our efforts to achieve the value potential of IMMU-132."

To date, the Company has:

● Advanced IMMU-114 in clinical trials and presented results at peer-reviewed clinical meetings (2015 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) and 2016 Pan Pacific Lymphoma Conference);

● Completed the Phase 2 trial of its solid cancer ADC, labetuzumab govitecan (IMMU-130), in patients with advanced, metastatic, colorectal cancer;
● Consulted with the FDA on the Phase 3 registration trial for IMMU-130 in patients with advanced, refractory, colorectal cancer;

● Advanced the Company’s development of IMMU-140, an antibody-drug conjugate (ADC) using the Company’s proprietary SN-38 conjugation technology together with the IMMU-114 humanized antibody, presenting first preclinical results at the 2016 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper); and

● Continued to establish, expand and explore our robust pipeline of potential treatments, including a novel, proprietary methodology to harness the patient’s own immune system to treat cancer with bispecific antibodies retargeting T cells (immuno-oncology program).
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CLINICAL PROGRAMS:
IMMU-130
This ADC contains the exact same linker + drug as IMMU-132, but employs a different antibody, labetuzumab. The antibody recognizes carcinoembryonic antigen (CEA, or CEACAM5), which is elevated in over 85% of patients with metastatic colorectal cancer (mCRC). Enrollment into a Phase 2, single-arm study in about 91 patients with mCRC has been completed. Promising activity in heavily-pretreated patients (median five prior therapies and all treated with irinotecan) were reported. In patients receiving the 10 mg/kg dose on days 1 and 8 of 21-day cycles, the median progression-free survival (PFS) was 4.6 months, and the median overall survival (OS) was 9.2 months. This compares favorably to results with regorafenib, which had a 3rd line median PFS of 1.9 months and an OS of 6.4 months. Although there were no partial responses (PRs) with IMMU-130 at this dose level/schedule, 87% of these patients had stable disease (SD). Immunomedics states that it will continue to follow patients in this Phase 2 study and will continue discussions with the regulatory authorities on the design of a future Phase 3 clinical trial.

Epratuzumab
To date, epratuzumab (humanized anti-CD22 antibody) has been administered to more than 2,000 patients with non-Hodgkin lymphoma (NHL), acute lymphoblastic lymphoma (ALL), and lupus. Clinical studies showed that it could be combined with rituximab, an anti-CD20 antibody, resulting in improved efficacy, which is the rationale leading to the Company developing bispecific antibodies against both CD22 and CD20 (discussed below). Currently, epratuzumab is being evaluated in a Phase 3 clinical trial in pediatric patients with ALL. This long-term, randomized study will enroll 612 patients, with the primary endpoint of PFS at four years. The IntReALL consortium, based in Berlin, Germany, is sponsoring this study, supported by a program grant from the European Union. The Company provides epratuzumab under a reimbursement program for the manufacturing costs.

Veltuzumab
The Company’s 2nd generation (humanized) anti-CD20 antibody, veltuzumab, was constructed with one amino acid difference in the binding site compared to rituximab, and has different framework regions due to humanization. Because of this structural change, functional difference compared to rituximab were observed during development, including veltuzumab’s binding to CD20 3-times longer, increased complement-dependent cytotoxicity (CDC), and improved survival in lymphoma xenograft models when compared to rituximab. This CD20 antibody has been formulated in subcutaneous (sc) dosing and has been evaluated in patients with NHL and immune thrombocytopenia (ITP), and has been administered under compassionate use in patients with lupus and pemphigus. Promising clinical results in over 200 patients receiving active and convenient sc dosing positions this program for advancement into controlled trials, alone and in combination with other agents. The indications would be patients with hematological malignancies and autoimmune diseases. The Company’s unique sc formulation has been patented.

Milatuzumab
Milatuzumab is a humanized anti-CD74 antibody targeting CD74 present on antigen-presenting cells, including B cells and dendritic cells. The Company is studying milatuzumab (sc formulation) in patients with lupus, under a U.S. Department of Defense grant. Previously, milatuzumab was studied as a monotherapy and in combination with veltuzumab, in patients with relapsed, refractory NHL, as well as a monotherapy in patients with advanced and refractory multiple myeloma; it showed activity in both disease settings. In a Phase 1b open-label study, patients with lupus received a dose per week for four weeks of milatuzumab, and were then assessed for disease activity using BILAG and SELENA-SLEDAI scoring systems. Results presented at EULAR in 2016 included all 10 patients enrolled showed a decrease in disease activity in at least one body system. Suppression of disease activity extended for 24 weeks in most patients. Injection reactions were mild-moderate. This has now moved into a double-blind, placebo-controlled, expansion phase, to confirm the activity of sc milatuzumab in this population, and continues to be supported by the U.S. Department of Defense.

IMMU-114
This 2nd generation anti-HLA-DR humanized antibody is an IgG4 immunoglobulin, administered by sc injection, and designed to reduce toxicities (severe infusion reactions) seen with prior IgG1 antibodies administered intravenously. Initial clinical studies in NHL and chronic lymphocytic leukemia (CLL) patients are continuing, with activity reported after patients had failed therapy with rituximab. Treatment cycles are now given repeatedly in a dose-determining clinical trial.

PRECLINICAL PROGRAMS:
IMMU-132 Preclinical Development (PARP Inhibitors/Chemotherapy Combinations)
Based on a preclinical study, the encouraging efficacy observed with IMMU-132 in animal models were presented, demonstrating the potential for improved therapeutic results when combined with agents that inhibit DNA repair pathways, both in mutated and wild-type BRCA1/2. Results from this preclinical study were published online in Clinical Cancer Research, a major peer-reviewed journal in cancer research and one of the official publications of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). Company scientists are also studying why cancer cells that express Trop-2 respond differentially to IMMU-132, in an effort to enhance the therapeutic effects clinically. Results suggest that different degrees of tumor resistance may be overcome, which could have a major impact on future clinical results.

IMMU-140 Preclinical Development
IMMU-140 is an ADC comprising SN-38 conjugated to IMMU-114 (anti-HLA-DR humanized antibody). It has been shown that the ADC possesses both the functional activities of the unconjugated antibody, IMMU-114, and the toxic effects of selective delivery of SN-38 to tumors, thus having a dual function. At the recent 2016 annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), the Company’s scientists showed that this dual activity resulted in more potent antitumor effects compared to IMMU-114, and that IMMU-140 had potent activity against five hematological neoplasms grown in cell culture and in suitable mice: NHL, CLL, ALL, multiple myeloma, and acute myeloid leukemia. IMMU-140 also targets some solid cancers not under investigation by the Company’s other two ADCs; namely, malignant melanoma and glioblastoma multiforme. This ADC is completing studies necessary to transfer it to clinical trials.

Bispecific Antibody Technology
The Company reported on the Dock-N-Lock (DNL) technology for making multi-valent antibody constructs, including CD22-CD20 bispecific antibodies, and the potential therapeutic indications in NHL, CLL, ALL, and multiple autoimmune diseases. By targeting two different receptors on circulating malignant B cells or B cells implicated in autoimmunity, the Company has shown enhanced potency compared to the parental antibodies targeting either CD22 or CD20. Moreover, these new constructs appear to have less destruction of normal B cells needed for immunity than the parental anti-CD20 antibody or other anti-CD20 antibodies currently available.

T-cell Retargeting
The Company presented preclinical data on a DNL-derived bispecific antibody for T-cell redirected killing of various hematological and solid tumors. This construct comprises the bivalent binding of CD19 or Trop-2 and monovalent CD3 recruitment of T cells on many different types of hematological and epithelial cancers, respectively.