Immunomedics (IMMU) is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, autoimmune disorders and other serious diseases. The company's advanced proprietary technologies allow it 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 six clinical-stage product candidates.¹

The company believe that each of its antibodies has therapeutic potential either when administered as a naked antibody or when conjugated with chemotherapeutics, therapeutic radioisotopes (radiolabeled), cytokines or other toxins to create unique and potentially more effective treatment options. The attachment of various compounds to antibodies is intended to allow the delivery of these therapeutic agents to tumor sites with better specificity than conventional chemotherapy or radiation therapy approaches. This treatment method is designed to reduce the total exposure of the patient to the therapeutic agents, which ideally minimizes debilitating side effects.

The company's 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 toxicities that are usually found with conventional administration of these chemotherapeutic agents. The company's 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 (“CRC”), respectively. IMMU-132 is its lead product candidate and has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (the “FDA”) for the treatment of patients with metastatic triple-negative breast cancer (“mTNBC”) who have failed at least two prior therapies for metastatic disease.

Following the election of a new Board of Directors at its Annual Meeting of Stockholders held on March 3, 2017, the company embarked on a new corporate strategy focused on bringing IMMU-132 to the market on its own in the United States for the benefit of patients with mTNBC and the creation of value for its stockholders. To that end, the company plan to submit a BLA to the FDA for accelerated approval of IMMU-132 in mTNBC as planned during the first quarter of 2018. To fulfil part of the accelerated approval requirements, the company also initiated and dosed the first patient into the Phase 3 ASCENT trial of IMMU-132 for mTNBC during the fourth quarter of calendar year 2017.

The company's financial resources are adequate to sustain the Company’s operations and research and development programs for at least the next twelve months at a level of activity sufficient to support the filing of the BLA; to continue manufacturing IMMU-132 at a large scale; to prepare for commercial operations in the U.S.; to continue the Phase 3 ASCENT trial of IMMU-132 for mTNBC; and to initiate preparations to market IMMU-132 to mTNBC patients in the U.S.

The company believe its current focus on commercializing IMMU-132 as a third-line therapy for patients with mTNBC is also the key to opening the door to further potential commercial opportunities in the future including developing IMMU-132 in earlier lines of therapy in mTNBC, as a monotherapy or in combination therapies, as well as expansion of IMMU-132 into other indications beyond mTNBC, such as urothelial cancer (“UC”), small-cell lung cancer (“SCLC’), and non-small-cell lung cancer (“NSCLC”). It’s only by proving IMMU-132 in mTNBC that the company can explore, expand into, and potentially capitalize on these new opportunities. While its immediate focus is on commercializing IMMU-132, on its own, in the U.S. and potentially European markets; Immunomedics is alert to opportunities to commercialize IMMU-132 in certain other regional markets; and Immunomedics is also open to business development opportunities to develop other pipeline assets.

These other product candidates, which target solid tumors and hematologic malignancies, as well as other diseases, are in various stages of clinical and pre-clinical development. They include other ADCs such as IMMU-130 (labetuzumab govitecan), which binds the CEACAM5 antigen expressed on colorectal and other solid cancers, and IMMU-140 that targets HLA-DR for the potential treatment of liquid cancers; IMMU-114, the parental antibody in IMMU-140 that targets the HLA-DR receptor; combination therapies involving its ADCs; 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® (“DNL®”) protein conjugation technology. The company believe that its portfolio of intellectual property provides commercially reasonable protection for its product candidates and technologies. In addition, Immunomedics has a research collaboration with Bayer to study epratuzumab as a thorium-227-labeled antibody and an ongoing collaboration with an independent cancer study group to evaluate epratuzumab in combination with chemotherapy in a large, randomized, Phase 3 trial in children with relapsed acute lymphoblastic leukemia (“ALL”).

The development and commercialization of successful therapeutic products is subject to numerous risks and uncertainties including, without limitation, the following:

• we may be unable to obtain additional capital through strategic collaborations, licensing, issuance of convertible debt securities or equity financing in order to continue its research and secure regulatory approval of and market its drug;
• the type of therapeutic compound under investigation and nature of the disease in connection with which the compound is being studied;
• The company's ability, as well as the ability of its partners, to conduct and complete clinical trials on a timely basis;
• the time required for it to comply with all applicable federal, state and foreign legal requirements, including, without limitation, its receipt of the necessary approvals of the FDA, if at all;
• the financial resources available to it during any particular period; and
• many other factors associated with the commercial development of therapeutic products outside of its control.

Research and Development

As of September 30, 2017, the company employed 8 professionals in its research and development departments, 27 professionals in its pre-clinical and clinical research departments and 74 professionals in its operations, manufacturing and quality control departments. In addition to salaries and benefits, the other costs associated with research and development include the costs associated with producing biopharmaceutical compounds, laboratory equipment and supplies, the costs of conducting clinical trials, legal fees and expenses associated with pursuing patent protection, as well as facilities costs.

At any one time its scientists are engaged in the research and development of multiple therapeutic compounds. Because the company do not track expenses on the basis of each individual compound under investigation, but rather aggregate research and development costs for accounting purposes, it is not possible for investors to analyze and compare the expenses associated with unsuccessful research and development efforts for any particular fiscal period, with those associated with compounds that are determined to be worthy of further development. This may make it more difficult for investors to evaluate its business and future prospects.

Clinical Pipeline Update

The following is an update of the status of its clinical trials.

Antibody-Drug Conjugates (ADCs)

Immunomedics has two ADC product candidates currently in clinical development focusing on the treatment of patients with metastatic solid tumors. The first ADC program, IMMU-132, is an anti-TROP-2-SN-38 ADC currently being evaluated in patients with a variety of solid tumors, including Phase 3 ASCENT trial for patients with mTNBC who have failed at least two prior therapies. IMMU-130, the second agent from its ADC program, is an anti-CEACAM5-SN-38 ADC currently in development for the treatment of metastatic CRC.

IMMU-132

IMMU-132 has been studied in over 500 diverse cancer patients in more than 15 types of solid cancers, with the dose of 10 mg/kg given on days 1 and 8 of repeated 21-day cycles being the established dose regimen. IMMU-132 received Breakthrough Therapy Designation from the FDA for the treatment of patients with mTNBC who have failed at least two prior therapies for metastatic disease. The FDA has also granted IMMU-132 Fast Track designation for the treatment of patients with mTNBC and for patients with SCLC, or NSCLC. IMMU-132 has also been designated an orphan drug by the FDA for the treatment of patients with SCLC or pancreatic cancer in the U.S. and by the European Medicines Agency (“EMA”) for the treatment of patients with pancreatic cancer in the European Union.

Currently, clinical development of IMMU-132 focuses on a number of select types of solid cancers including mTNBC, UC, SCLC, NSCLC, and certain other cancers.

Initial results from a single-arm Phase 2 study in heavily-pretreated patients with mTNBC were published in the Journal of Clinical Oncology (J Clin Oncol. 35(19):2141-2148 2017). This study was updated by its clinical investigator at the 2017 Investor R&D Day to show IMMU-132 produced tumor shrinkage from baseline measurements in 81% of 85 assessable mTNBC patients, with two confirmed complete responses (“CRs”) and 23 confirmed partial responses (“PRs”) for a confirmed objective response rate (“ORR”) of 29%. An abstract on results from this Phase 2 study was submitted and accepted for oral presentation at the 2017 San Antonio Breast Cancer Symposium in December.

The final results in mTNBC will be part of a BLA package, which the Company plans to submit to the FDA for the accelerated approval of IMMU-132 as a third-line treatment for patients with mTNBC as planned during the first quarter of 2018. A prerequisite for FDA acceptance of the BLA filing is to have a confirmatory Phase 3 trial to be underway at the time of BLA submission. To that end, the company initiated and dosed the first patient in the confirmatory Phase 3 ASCENT study in November 2017, thereby satisfying FDA’s requirement.

The company's financial resources are adequate to sustain the Company’s operations and research and development programs for at least the next twelve months at a level of activity sufficient to support the filing of the BLA; to continue manufacturing IMMU-132 at a large scale to prepare for commercial operations in the U.S. marketplace; to conduct the Phase 3 ASCENT trial of IMMU-132 for mTNBC; and to initiate preparations to market IMMU-132 to mTNBC patients in the U.S.

In metastatic UC, IMMU-132 was found to be active in patients who have relapsed or are refractory to chemotherapies and immune checkpoint inhibitors (“IOs”), as reported by its clinical investigator at the European Society for Medical Oncology Congress held during September 2017. The confirmed ORR among forty-one intention-to-treat (“ITT”) patients was 34% (14/41), including two confirmed CRs and twelve confirmed PRs. While eight of the fourteen responders are ongoing and are still receiving treatment, including four long-term responses greater than 1 year and two currently ongoing at 15 and 22 months, the median duration of response (“DOR”) at the time of data cutoff was 12.6 months (95% confidence interval [CI], 7.5 to 12.9 months). Median progression-free survival (“PFS”) at 80% data maturity was 7.1 months (95% CI, 5.0 to 10.7 months). The enrolled cohort included fourteen patients who progressed after prior IO therapy, eleven of whom received IMMU-132 as the fourth or later line of therapies. Despite the late-stage setting, the confirmed ORR in this subset of patients was 29% (4/14), with median PFS of 5.4 months (95% CI, 1.9 to 7.2 months) but median overall survival (“OS”) was not met. All four responders in this subgroup had three or more prior therapies before IMMU-132.

Results with IMMU-132 in SCLC and NSCLC were recently published in medical journals. For SCLC, as reported in the journal Clinical Cancer Research (Clin Cancer Res. 23(19):5711-5719, 2017), 60% of patients showed tumor shrinkage from baseline computed tomography (“CT”) measurements. On an ITT basis (N= 50), the ORR was 14% (17% for 10 mg/kg group) and the median DOR was 5.7 months. Median PFS and median OS were 3.7 months and 7.5 months, respectively. There was a suggested improvement in PR and PFS with IMMU-132 in second-line patients who were sensitive to frontline therapy, but no difference between frontline chemosensitive versus chemoresistant patients in the overall population.

In NSCLC, in the response-assessable study population (N = 47), which had a median of 3 prior therapies (range, 2-7), 67% of patients showed a shrinkage from baseline CT measurements. The confirmed ORR was 19% and the median DOR was 6.0 months (95% CI, 4.8 to 8.3 months). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after IO therapy. On an ITT basis (N=54), median PFS was 5.2 months (95% CI, 3.2 to 7.1 months) and median OS was 9.5 months (95% CI, 5.9 to 16.7 months). More information on this study can be obtained from the Journal of Clinical Oncology (J Clin Oncol. 35(24):2790-2797, 2017).

The safety profile of IMMU-132 in these patients with solid cancers was manageable. Grade 3 or higher adverse events were similar and limited to neutropenia, fatigue, diarrhea, and anemia. Despite repeated dosing, no antibodies to the drug conjugate or its components were detected on serial blood collections. Trop-2 tumor staining was not required for patient selection, due to greater than 80% expression.

Immunomedics has an extensive intellectual property portfolio protecting IMMU-132. Specifically, 37 patents were issued in the U.S. and 22 foreign patents were issued covering composition of matter, synthesis and uses. Certain patents relating to the protein sequence of the hRS7 antibody used in IMMU-132 expire in 2017 in the U.S. and 2023 overseas. Patents to compositions and use of the CL2A linker incorporated in IMMU-132 expire between 2023 and 2029 in the U.S. and overseas. Other patents relating to use of hRS7 for cancer therapy, including the SN-38 conjugated form of hRS7 used in IMMU-132, extend to 2036. Additionally, Immunomedics is entitled to extend the term of its key patent for up to 5 more years. Outside the U.S., patents were issued in Australia, Canada, China, Europe, Israel, Japan, Mexico, South Korea and other key global markets.

IMMU-130

The company's second investigational solid-tumor ADC involves its anti-CEACAM5 antibody labetuzumab, conjugated to SN-38. The agent is currently being studied in patients with metastatic CRC who had received at least one prior irinotecan-containing regimen and had an elevated blood titer of carcinoembryonic antigen.

In a Phase 2 study examining dosing schedules, safety and any evidence of efficacy, a total of 86 patients with progressive disease who had received prior therapy with an irinotecan-containing regimen, half of whom had completed 5 prior lines of therapy, were enrolled to receive labetuzumab govitecan either once-weekly at 8 and 10 mg/kg, or twice-weekly at 4 and 6 mg/kg, on weeks 1 and 2 of 3-week repeated cycles. Results from this study were published in the Journal of Clinical Oncology (J Clin Oncol. 35(29):3338-3346, 2017).

Median PFS and OS for patients who received once-weekly labetuzumab govitecan at the 8 or 10 mg/kg dose level are summarized below.

• Treatment response was evaluated in accordance with the rules set by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) using CT as the imaging tool for tumor size measurements.

All of these patients had received prior irinotecan therapy. Interestingly, 23 patients had prior treatment with regorafenib, which was approved in the U.S. for the treatment of patients with previously-treated mCRC based on a median PFS of 2.0 months and a median OS of 6.4 months. In this subset of the patients, the median PFS and OS with labetuzumab govitecan were 4.0 and 6.7 months, respectively.

Labetuzumab govitecan was well-tolerated, with a manageable toxicity profile. Major toxicities (Grade >3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). Anti-drug or anti-antibody antibodies were not detected.

Since there was no significant difference in safety and efficacy between the two once-weekly dosing schedules, for patient’s convenience, once-a-week dosing was chosen for future studies in metastatic CRC patients. Although certain patents relating to labetuzumab used in labetuzumab govitecan expired in 2016, other patents relating to use of labetuzumab for cancer therapy, including the SN-38 conjugated form of labetuzumab used in labetuzumab govitecan, extend to 2033.

Other Product Candidates

Immunomedics has additional potential products for the treatment of cancer and autoimmune diseases including epratuzumab, its anti-CD22 antibody; veltuzumab, its anti-CD20 antibody; milatuzumab, its anti-CD74 antibody; and IMMU-114, a humanized anti-HLA-DR antibody.

Epratuzumab

Immunomedics has a research collaboration with Bayer to study epratuzumab as a thorium-227 labeled antibody. Targeted Thorium Conjugates (“TTCs”) represent a new technology directing the power of the alpha-particle selectively towards tumor cells. The high linear energy transfer of the alpha particle generated by decay of the radionuclide thorium-227 induces double-strand DNA breaks causing cell death in targeted tumor cells.

The company's corporate partner, Bayer, is enrolling patients with relapsed or refractory CD22-positive non-Hodgkin lymphoma (“NHL”) into a Phase 1 clinical trial evaluating epratuzumab labeled with thorium-227.

This study is focusing on patients with diffuse large B-cell lymphoma and potentially follicular lymphomas who have been previously treated with, or are not considered candidates for available therapies. An overview of the TTC platform and the CD22 TTC program was provided in an oral presentation by Bayer at the 2016 AACR Annual Meeting.

The company also have an ongoing collaboration with the IntReALL, Inter-European study group who is conducting a large, randomized, Phase 3 trial combining epratuzumab with chemotherapy in children with relapsed ALL at clinical sites in Australia, Europe, and Israel. This Phase 3 study, which is partially funded by the European Commission, assesses the efficacy and safety of this combination therapy using event-free survival as the surrogate for survival, the primary endpoint.

Although certain patents to the epratuzumab protein sequence expired in 2014 in the U.S. and in 2015 overseas, other issued patents to therapeutic use of epratuzumab extend to 2018-2023 for cancer and 2020 for autoimmune disease. The method of preparing concentrated epratuzumab for subcutaneous administration is covered by another patent family with expiration in the United States in 2032.

Veltuzumab

Veltuzumab is a humanized monoclonal antibody targeting CD20 receptors on B lymphocytes currently in clinical development for the treatment of NHL and autoimmune diseases. The Office of Orphan Products Development of the FDA has granted orphan status for the use of veltuzumab for the treatment of patients with immune thrombocytopenia (“ITP”) and pemphigus. Immunomedics has studied the subcutaneous formulation of veltuzumab in patients with ITP in a Phase 1/2 trial, which was designed to evaluate different dosing schedules. This trial has completed patient accrual and patients are being followed for up to five years. In oncology, Immunomedics has completed a National Cancer Institute-funded Phase 2 study in patients with aggressive NHL in combination with 90Y-epratuzumab tetraxetan.

Immunomedics is currently evaluating various options for further clinical development of veltuzumab in ITP and other autoimmune disease indications, including pemphigus, as well as in oncology, including licensing arrangements and collaborations with outside study groups.

Milatuzumab

Milatuzumab is the first anti-CD74 antibody that has entered into human testing and Immunomedics has completed initial Phase 1studies in patients with relapsed multiple myeloma, NHL or chronic lumphocytic leukemia (“CLL”). It has received orphan drug designation from the FDA for the treatment of patients with multiple myeloma or CLL.

The anti-CD74 antibody is also being studied subcutaneously in a Phase 1b study in patients with active systemic lupus erythematosus supported by a three-year research grant from the Department of Defense with a potential funding of $2 million. First results from the open-label study were presented at a poster session during the 2016 annual European League Against Rheumatism Congress. Based on early encouraging results, the study has been expanded into a double-blind, placebo-controlled 30-patient trial to confirm the activity of milatuzumab in this population and have received approval from the Department of Defense for an increased budget to support the expansion.

IMMU-114

IMMU-114 is a novel humanized antibody directed against an immune response target, HLA-DR, currently in Phase 1development for the treatment of patients with B-cell and other cancers. HLA-DR is a receptor located on the cell surface whose role is to present foreign objects to the immune system for the purpose of eliciting an immune response. Increased presence of HLA-DR in hematologic cancers has made it a prime target for antibody therapy. The anti-HLA-DR antibody is being evaluated as a subcutaneously administered monotherapy for patients with NHL or CLL in a Phase 1 study. Results from this study were presented at the December 2015 Annual Meeting of the American Society of Hematology and updated at the 2016 Pan Pacific Lymphoma Symposium. IMMU-114 showed early evidence of efficacy in both NHL and CLL and was well tolerated by patients, with only local skin reactions at the injection sites, which were all mild to moderate and transient.

References

1. ^ https://fintel.io/doc/sec-immu-immunomedics-10k-2018-august-23-17962