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Alkermes Initiates Clinical Evaluation of Novel Immuno-Oncology Drug Candidate ALKS 4230 in Combination With PD-1 Inhibitor Pembrolizumab

On September 10, 2018 Alkermes plc (Nasdaq : ALKS ) reported that it has expanded its ongoing phase 1 study for ALKS 4230, the company’s immuno-oncology drug candidate, to evaluate its safety and anti-tumor activity when administered in combination with the FDA-approved PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with advanced solid tumors (Press release, Alkermes, SEPT 10, 2018, View Source [SID1234529370]). ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

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"The emergence of therapeutics targeting the PD-1 pathway has revolutionized the field of oncology, yet there remains significant opportunity to improve the clinical benefit of checkpoint inhibitors for the treatment of solid tumors. There is strong scientific rationale supporting the combination of PD-1 pathway inhibition with cytokine therapy such as ALKS 4230 to activate the body’s own immune system to fight cancer, and the potential synergies of ALKS 4230 and pembrolizumab on anti-tumor activity may expand treatment options for patients in a variety of tumor settings," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "We’ve accelerated clinical evaluation of ALKS 4230 in combination with pembrolizumab based on data from our ongoing monotherapy dose-escalation stage of the phase 1 study, where ALKS 4230 demonstrated dose-dependent pharmacodynamic effects on circulating natural killer cells and CD8+ T cells, and minimal and non-dose dependent effects on immunosuppressive regulatory T cells. These data validate our design rationale for ALKS 4230, and we look forward to sharing initial data from our dose-escalation cohorts at a medical meeting later this year."

Evaluation of the safety and anti-tumor activity of ALKS 4230 in combination with pembrolizumab will be assessed in certain PD-1 approved tumor types in both refractory and treatment naïve patients, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, gastric cancer, urothelial carcinoma and microsatellite instability-high cancers. Melanoma and renal cell carcinoma will also be evaluated in the cohort of treatment naïve patients. The combination of ALKS 4230 and pembrolizumab will also be assessed in certain PD-1 unapproved tumor types, including colorectal cancer, triple-negative breast cancer, ovarian carcinoma, soft tissue sarcomas, and patients with metastatic NSCLC whose tumors express low or undetectable PD-L1 (tumor proportion score <1%).

About the Phase 1 Study

The Alkermes-sponsored phase 1 study for ALKS 4230 includes three distinct stages: the ongoing monotherapy dose-escalation stage, the planned monotherapy dose-expansion stage and the newly initiated combination therapy stage with pembrolizumab. The dose-escalation stage is designed to determine a maximum tolerated dose of ALKS 4230 in a monotherapy setting and to identify the optimal dose range of ALKS 4230 based on measures of immunological-pharmacodynamic effects. Upon completion of the dose-escalation stage, the company expects to initiate the monotherapy dose-expansion stage in up to 42 patients with renal cell carcinoma or melanoma. The newly initiated combination therapy stage of the phase 1 study will assess the safety profile and anti-tumor activity of ALKS 4230 with pembrolizumab in up to 148 patients with select advanced solid tumors. This combination therapy stage will be run independent of, and concurrently with, the monotherapy dose-escalation and dose-expansion stages of the trial.

Anti-tumor response and duration of response assessments in the dose-expansion and combination stages of the phase 1 study will be based on investigator-assessed, immune-related response (irRC) criteria and independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.

About ALKS 4230

ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects while overcoming limitations of existing IL-2 therapy, which activates both immunosuppressive and tumor-killing immune cells.

CCAB And Triumvira Immunologics Announce Triumvira’s License Agreement with University of Toronto for the Discovery of Antibody Drug Development Candidates

On September 10, 2018 The Centre for the Commercialization of Antibodies and Biologics (CCAB) and Triumvira Immunologics, Inc. (Triumvira), reported a new licensing agreement between the University of Toronto (U of T) and Triumvira (Press release, Triumvira Immunologics, SEP 10, 2018, View Source [SID1234529369]). The agreement provides Triumvira with an exclusive license for antibodies discovered at the U of T on specified therapeutic targets. Triumvira is a privately held biopharmaceutical company with R&D facilities in Hamilton, ON, that is developing a novel platform for engineering T cells to attack multiple cancer types.

CCAB is the assigned agent for the U of T for the commercialization of a large portfolio of human antibodies. Under the terms of the agreement, U of T will receive up-front fees, milestone payments and royalty payments on net sales of products on three therapeutic targets: BCMA, ROR1 and one undisclosed target.

"We are very pleased to be working with The Centre for the Commercialization of Antibodies and Biologics and the University of Toronto under this new licencing agreement," said Paul Lammers, MD, MSc, President and Chief Executive Officer of Triumvira. "This partnership is critical as we work to bring new treatments to patients in need through our proprietary T Cell-Antigen Coupler (TAC) technology."

Triumvira’s lead therapeutic candidate, TAC01-CD19, is a CD19-directed T cell product for the treatment of B cell malignancies and is anticipated to enter Phase I clinical trials in H1 2019 in patients with diffuse large B cell lymphoma (DLBCL). The company is also developing a series of products for solid tumors.

"Collaboration is a vital part in the development of new therapeutics. These types of agreements continue to strengthen the connection between academia and industry and help to translate the wealth of scientific knowledge from the laboratories at our world-class universities to the clinic," CCAB Chief Executive Officer Robert Verhagen said.

Innovent’s Anti-CD47 Antibody IBI188 Receives IND Approval in China

On September 9, 2018 Innovent Biologics (Innovent), a world-class China-based biopharmaceutical company that develops and commercializes high quality drugs, reported that its IND application for IBI188, a fully human anti-CD47 monoclonal antibody (mAb) drug candidate, has been approved by the National Medical Products Administration (NMPA, formerly known as CFDA) for clinical trials (Press release, Innovent Biologics, SEP 9, 2018, View Source [SID1234529358]). Innovent will launch several clinical trials based on this mAb drug to assess its safety and efficacy for multiple tumor types, including non-Hodgkin’s lymphoma and ovarian cancer. This is the fourth IND approval the company has received this year, including anti-CTLA-4 mAb, anti-RANKL mAb, anti-OX40 mAb and anti-CD47 mAb.

As one of the key targets in the field of anti-tumor immunotherapy, CD47 is regarded by many experts to have the possibility of becoming the next "star" in the field of immuno-oncology following the ground-breaking success of PD1 / PD-L1 antibodies. The IND approval signals that Innovent’s discovery and development on CD47 has advanced IBI188 as a leading player for this target to enter into clinical development stage.

"Innovent, with a relentless focus on innovation and quality, has developed programs that are advancing into cutting edge drug development frontiers. We hope that through our efforts, we can advance the field of cancer treatment, provide better treatment options to increase patients’ survival rate and improve their quality of life," said Michael Yu, Founder, Chief Executive Officer and Chairman.

"Emerging data suggests that CD47 antibody in combination with other treatments, including anti-PD-1 monoclonal antibodies, could result in higher levels of anti-tumor efficacy. Innovent’s current rich pipeline will allow multiple drug combinations with IBI188 creating many opportunities to achieve breakthroughs in cancer treatment to meet more unmet patient needs in the future," said Dr. Kerry Blanchard, Chief Scientific Officer of Innovent.

CD47 is one of the most important targets in the field of immuno-oncology. The development of anti-CD47 monoclonal antibody has recently attracted much attention. Innovent will be among one of a few companies pursuing the development of an anti-CD47 antibody in the early clinical stage.

About IBI188

IBI188 is an anti-CD47 IgG4 monoclonal antibody developed by Innovent with independent intellectual property rights. Both in vitro and in vivo experiments showed that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the CD47-SIRPα signaling pathway, inhibit the "Don’t Eat Me" signal, and promote the phagocytosis of tumor cells by macrophages, thereby exerting an anti-tumor effect. It has stronger receptor blocking ability than similar drugs. Innovent will launch several clinical trials to assess its safety and efficacy for multiple tumor types, including non-Hodgkin’s lymphoma and ovarian cancer.

Compugen Announces First Patient Dosed with COM701, a First-in-Class Cancer Immunotherapy Antibody, in Phase 1 Clinical Trial

On September 7, 2018 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that the first patient has been dosed in its Phase 1 clinical trial of COM701, a first-in-class cancer immunotherapy antibody targeting PVRIG (Press release, Compugen, SEP 7, 2018, View Source [SID1234529393]). PVRIG is a novel immune checkpoint identified by Compugen using its computational discovery capabilities.

"Dosing the first patient with COM701, a first-in-class drug opportunity targeting a novel immune checkpoint we identified with our computational predictive platform, is a landmark event for us. We look forward to clinically testing it," stated Anat Cohen-Dayag, Ph.D., Compugen’s President and CEO. "It also serves as a proof of concept for our discovery capabilities and marks Compugen as a leader in the field of computational discovery. We will continue leveraging this core competency in expanding our therapeutic pipeline and achieving our corporate and business goals."

Drew W. Rasco, M.D., Associate Director of Clinical Research at the START Center for Cancer Care and a Principal Investigator in the Phase 1 COM701 study, said, "Immunotherapy has revolutionized the landscape for oncology treatments by providing a new treatment option leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can result in the development of new cancer immunotherapies for non-responsive and refractory patients. COM701 preclinical data suggest that the newly-discovered PVRIG pathway may be a dominant pathway in certain cancer subpopulations, including those that are unresponsive to PD‑1 or PDL-1 inhibitors. As such, it is important to evaluate COM701 in clinical trials with these patient populations who have exhausted available standard therapy."

Henry Adewoye, M.D., Chief Medical Officer of Compugen, said, "COM701 is a promising and differentiated asset in the crowded landscape of immuno-oncology trials. Our clinical and biomarker strategy for testing COM701 is premised on a robust biological rationale which suggests that targeting PVRIG may be necessary to induce a sufficient anti-tumor immune response in cancer patient subpopulations where both the PVRIG and TIGIT pathways are operative, thereby addressing the high unmet need of relapsed and refractory disease following treatment with existing immunotherapies. We look forward to exploring the full clinical potential of COM701."

This Phase 1 open-label clinical trial is designed to assess the safety and tolerability of administering escalating doses of COM701 monotherapy as well as combination administration with a PD-1 inhibitor in patients with advanced solid tumors. Additionally, the trial will evaluate evidence of preliminary antitumor activity of COM701 as a monotherapy as well as in combination with a PD-1 inhibitor in patients with selected tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. The study will be conducted in multiple leading oncology clinical centers in the United States, which are expected to enroll approximately 140 patients. Additional information will be available shortly at www.clinicaltrials.gov.

About COM701
COM701 is a humanized hybridoma antibody that binds with high affinity to PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen, blocking its interaction with its ligand, PVRL2. Blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. In addition, COM701 combined with antagonist anti-PD-1 antibodies has demonstrated synergistic effects on human T cell stimulation, indicating the potential of these combinations to further enhance immune response against tumors.

Preclinical data for COM701 suggest that PVRIG may be a dominant checkpoint in diverse patient populations with tumors that express elevated PVRL2 as compared to expression of the TIGIT ligand PVR. This include patients with breast, endometrial, and ovarian cancers. In addition, expression studies show that PVRIG and TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as those noted above, as well as lung, kidney, and head & neck cancers. In these tumors the blockade of both TIGIT and PVRIG may be required to sufficiently stimulate an anti-tumor immune response, with or without additional PD-1 pathway blockade.

Advaxis Announces Pricing of Its Public Offering of Common Stock and Warrants

On September 7, 2018 Advaxis, Inc. (NASDAQ:ADXS) ("Advaxis" or the "Company") reported the pricing of an underwritten public offering of 16,666,666 shares of its common stock and warrants to purchase up to 14,166,666 shares of common stock (Press release, Advaxis, SEP 7, 2018, View Source [SID1234529381]). Each share of common stock is being sold together in a fixed combination with a warrant to purchase 0.85 shares of common stock. The warrants will be exercisable immediately, will expire six years from the date of issuance and will have an exercise price of $1.50 per share, subject to anti-dilution adjustments. The gross proceeds of the offering to the Company are expected to be approximately $20 million, before deducting the underwriting discounts and commissions and other estimated offering expenses, and excluding the exercise of any warrants.

The closing of the offering is expected to occur on or about September 11, 2018, subject to the satisfaction of customary closing conditions.

Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc. are acting as joint book-running managers for the offering.

The Company intends to use the net proceeds of the offering to fund its continued research and development initiatives in connection with expanding its product pipeline and for other general corporate purposes, including, but not limited to (i) progression of ADXS-HOT into clinical research in both monotherapy and combination therapy; (ii) investment in ongoing clinical research in ADXS-PSA and ADXS-NEO, both in monotherapy and combination therapy; and (iii) investment in ongoing clinical research with axalimogene filolisbac in head and neck cancer and other HPV associated cancers, including any wind down costs associated with ongoing trials.

The securities described above were offered by the Company pursuant to a "shelf" registration statement (File No. 333-226988) previously filed with the Securities and Exchange Commission (the "SEC") on August 23, 2018 and declared effective by the SEC on August 30, 2018.

A preliminary prospectus supplement relating to the offering was filed with the SEC on September 6, 2018 and is available on the SEC’s website at View Source The final prospectus supplement relating to the offering will be filed with the SEC and also will be available on the SEC’s website. Before investing in the offering, you should read each of the prospectus supplement and the accompanying prospectus in their entirety as well as the other documents that Advaxis has filed with the SEC that are incorporated by reference in the prospectus supplement and the accompanying prospectus, which provide more information about the Company and the offering. Copies of the final prospectus supplement and accompanying prospectus relating to this offering, when available, may be obtained from Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 6th Floor, New York, New York 10022, or by email at [email protected]; or Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, New York 10004, Telephone: (212) 667-8055, Fax: (212) 667-6141 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.