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Zymeworks Doses First Patient in Phase 1 Trial of ZW25, a Novel Bi-Specific Antibody for the Treatment of HER2-Expressing Cancers

On September 15, 2016 Zymeworks Inc., a biopharmaceutical company discovering and developing innovative multi-functional protein-based therapeutics, including bi-specific antibodies and drug conjugates for the treatment of cancer, reported that the first patient was dosed in a Phase 1 clinical trial of ZW25 for treatment of HER2-expressing tumors (Press release, Zymeworks, SEP 15, 2016, View Source [SID:SID1234515174]).

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As Zymeworks’ lead therapeutics program, ZW25 is a novel bi-specific antibody developed using the Company’s Azymetric platform. The compound targets two different epitopes (bi-paratopic targeting) of the human epidermal growth factor receptor 2 (HER2) protein, which is over-expressed on the surface of many tumor types, including certain breast, gastric, lung, and ovarian cancers.

"We are excited to have begun enrollment in this initial study of ZW25," said Diana Hausman, M.D., Zymeworks’ Chief Medical Officer. "No approved HER2-targeted therapies exist for many patients with HER2-expressing cancers and with its unique mechanism of action, ZW25 has the potential to address this significant unmet need."

ZW25 is being evaluated in the clinic for safety, as well as efficacy, in patients with tumors with low to moderate levels of HER2 expression. ZW25 is active in numerous in vivo models of HER2 low to high expressing cancers, including ovarian cancer, for which it has received Orphan Drug Designation from the FDA. ZW25 has demonstrated an acceptable safety profile in preclinical toxicology studies when administered at multiple dose levels using a once per week dosing schedule.

About ZW25

ZW25 is Zymeworks’ lead therapeutics program based on the Azymetric platform. It is an engineered bi-specific antibody that targets two different epitopes (bi-paratopic targeting) of the HER2 protein and confers its efficacy via multiple mechanisms of action, including: (i) enhanced antibody-mediated effector function resulting from the increased decoration of the tumor cell surface; (ii) increased blockade of the HER2 cellular growth signal by the dual engagement of HER2 epitopes; and (iii) increased removal of surface-expressed HER2 protein due to enhanced HER2 internalization upon antibody engagement. ZW25 is a best-in-class HER2-targeting antibody for a variety of tumors characterized by HER2 overexpression, including breast, gastric, ovarian, colorectal and non-small cell lung cancers. The FDA has granted Orphan Drug Designation to ZW25 for the treatment of ovarian cancer.

LION BIOTECHNOLOGIES ENTERS INTO EXCLUSIVE LICENSE AGREEMENT WITH POLYBIOCEPT AB AND CLINICAL TRIALS AGREEMENT WITH THE KAROLINSKA UNIVERSITY HOSPITAL

On September 15, 2016 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocytes (TIL), reported that it has entered into an exclusive license agreement with PolyBioCept AB, a corporation organized under the laws of Sweden, and a related clinical trials agreement to sponsor two clinical studies in glioblastoma and pancreatic cancer at the Karolinska University Hospital in Sweden (Press release, Lion Biotechnologies, SEP 15, 2016, View Source [SID:SID1234515173]).

Under the terms of the license agreement, Lion gained exclusive worldwide rights to two international patent applications related to a specific combination of cytokines for use in the expansion, selection and enrichment of TIL products for the treatment of multiple cancer indications. Lion also has co-exclusive worldwide rights (with PolyBioCept) to make genetically engineered TIL using the cytokine cocktail for use in multiple cancer indications.

Under the terms of the clinical trials agreement, Lion will fund two clinical studies in glioblastoma and pancreatic cancer to be conducted at the Karolinska University Hospital in which TIL is manufactured using the licensed combination of cytokines.

"In addition to our ongoing efforts to develop treatments for patients with metastatic melanoma using TIL therapy, we are committed to expanding the use of TIL for patients with other solid tumors. We are excited to be working with PolyBioCept and the Karolinska University Hospital to treat glioblastoma and pancreatic cancer patients with TIL manufactured with a new combination of cytokines developed by researchers at the Karolinska Institute. Our partnership with Karolinska further positions Lion to be a leader in developing cell-based immunotherapies that can treat solid tumor indications," said Maria Fardis, PhD, MBA, Lion Biotechnologies President and Chief Executive Officer.

Dr. Markus Maeurer, head of the division Therapeutic Immunology (TIM), Department of Laboratory Medicine and senior physician at the center for allogeneic stem cell transplantation, Karolinska University Hospital, and Dr. Ernest Dodoo Deputy Head Division Therapeutic Immunology, director Neuro-Oncology Program and director Gamma Knife Program at the Department of Neurosurgery, Karolinska University Hospital said, "We are pleased to be working with Lion Biotechnologies in advancing the TIL technology through the conduct of two Phase I trials at the Karolinska University Hospital. These trials are aligned with the vision of the Karolinska University Hospital to make a significant contribution to the improvement of human health. We are pleased to offer these immunological therapies for glioblastoma and pancreatic cancer patients in need of individually-tailored care."

Lion will pay PolyBioCept $2.5 million in upfront payments under the exclusive license. Lion will also make additional payments (in cash and in shares of Lion’s common stock) upon achievement of certain clinical, regulatory and sales milestones. The clinical trials agreement calls for a total of $1.7 million to be paid to the Karolinska University Hospital and PolyBioCept to conduct the clinical trials in glioblastoma and pancreatic cancer.

Calithera Announces First Patient Dosed in a Phase I Study of CB-1158, the First-in-Class Inhibitor of the Immuno-Oncology Target Arginase

On September 15, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that the first patient has been dosed in a Phase I clinical trial assessing the safety and efficacy of CB-1158, a first-in-class arginase inhibitor for the treatment of advanced solid tumors (Press release, Calithera Biosciences, SEP 15, 2016, View Source [SID:SID1234515171]). Arginase is an enzyme in myeloid-derived suppressor cells (MDSCs), which prevents T-cell and natural killer (NK) cell activation in tumors.

"Arginase, when released by MDSCs, plays an important role in the inhibition of T-cell and NK-cell activation and proliferation, preventing immune-mediated anti-tumor activity. For example, in many solid tumors, including lung, colorectal, esophageal, bladder, head and neck, and kidney cancer, arginase-expressing MDSCs accumulate, establishing an immunosuppressive microenvironment by blocking the ability of T-cells and NK-cells to kill cancer cells. We believe that inhibitors of arginase can promote an anti-tumor immune response and augment the activity of checkpoint inhibitors," said Susan M. Molineaux, Ph.D., founder, Chief Executive Officer and President of Calithera Biosciences. "We look forward to reporting initial clinical results with this compound in 2017."

Arginase exerts its immunosuppressive effect by depleting the amino acid arginine in the tumor microenvironment and preventing activation and proliferation of the immune system’s cytotoxic T-cells and NK-cells. We believe that inhibitors of arginase activity promote an anti-tumor immune response by restoring arginine levels in the tumor and reversing this immunosuppressive metabolic checkpoint. The Phase I clinical trial will enroll patients with advanced solid tumors treated with CB-1158 as a monotherapy, as well as in combination with an anti-PD1 therapy.

Epizyme Earns $6 Million Milestone Payment from GlaxoSmithKline for Initiation of Clinical Development with First-in-Class PRMT5 Inhibitor

On September 15, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapeutics, reported it has earned a $6 million milestone payment from GlaxoSmithKline (GSK) (Press release, Epizyme, SEP 15, 2016, View Source [SID:SID1234515153]). The milestone payment follows GSK’s initiation of patient dosing in a Phase 1 clinical trial of GSK3326595 (formerly EPZ015938), a first-in-class protein arginine methyltransferase-5 (PRMT5) inhibitor discovered by Epizyme and licensed to GSK. PRMT5 is a protein methyltransferase that is associated with a number of human cancers.

"Epizyme has pioneered the discovery and development of epigenetic therapies for the treatment of cancer, with three agents discovered by Epizyme now in clinical development," said Robert Bazemore, President and Chief Executive Officer, Epizyme. "Our collaboration with GSK represents an important part of our strategy of partnering with industry leaders to extend the breadth of our epigenetic therapies while providing resources to help us accelerate our portfolio of assets. We look forward to GSK’s continued progress with this program."

GSK has initiated a Phase 1, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK3326595 in patients with solid tumors and non-Hodgkin lymphoma.

"The introduction of this PRMT5 inhibitor into the clinic by GSK is an exciting scientific achievement for Epizyme," said Robert A. Copeland, Ph.D., President of Research and Chief Scientific Officer, Epizyme. "This milestone reinforces the strength of our scientific capabilities, which have enabled us to expand our platform into new epigenetic target classes of potentially high importance in oncology. Through our collaborations with GSK and other biopharmaceutical companies, as well as our in-house research efforts, we have developed a number of novel epigenetic programs that we believe hold tremendous potential, including this first-in-class PRMT5 inhibitor."

About the Epizyme-GSK Collaboration

About PRMT5 and GSK3326595
PRMT5 is a protein arginine methyltransferase (PRMT) that is reported to have a role in diverse cellular processes, including tumorigenesis. PRMT5 overexpression is observed in cell lines and primary patient samples derived from a number of cancers, including lymphomas, lung cancer, breast cancer and colorectal cancer. GSK3326595 (formerly EPZ015938), a highly selective and orally bioavailable small molecule, is the first PRMT5 inhibitor and the third epigenetic investigational therapy derived from Epizyme’s proprietary discovery platform to enter the clinic.

Celsion Corporation Announces Positive DSMB Review of Phase 1b OVATION Study in Ovarian Cancer

On September 15, 2016 Celsion Corporation (NASDAQ:CLSN) reported that the independent Data Safety Monitoring Board (DSMB) has completed its safety review of data from the first three patient cohorts in the ongoing Phase Ib OVATION Study (Press release, Celsion, SEP 15, 2016, View Source [SID:SID1234515152]). Based on the DSMB’s recommendation, the study will continue as planned and the Company will proceed with dosing in its fourth and final patient cohort at an escalated dose. The OVATION Study is a dose-escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.

"The DSMB’s recommendation and the lack of any dose limiting toxicities in the trial to date underscore the improved tolerability of GEN-1 over recombinant IL-12 protein-based therapies," said Nicholas Borys, M.D., senior vice president and chief medical officer of Celsion. "The favorable safety profile we have seen thus far is consistent with the translational data that we reported earlier this year, which show that GEN-1 produces a sustained, localized secretion of IL-12 protein and avoids the high levels of systemic exposure which have limited the development of recombinant IL-12 therapies in the past."

"We could not be more excited to progress with the OVATION Study and look forward to reporting clinical findings from the third patient cohort, as well as translational data from the first two cohorts, early in the fourth quarter. Furthermore, we expect to report final data from this highly promising study in the first quarter of 2017," said Michael H. Tardugno, Celsion’s chairman, CEO and president. "We have been encouraged, as have been our Investigators, by the findings to-date in this difficult-to-treat patient population. As we have previously reported, all six patients in the first two cohorts experienced a clinically meaningful response, ranging from stable disease to one pathologically confirmed complete response. In addition, we saw sustained decreases of 90% or greater of the prospective indicator of the presence of ovarian cancer cells, CA-125 protein, in all patients, as well as highly impressive pathologically responses, which is associated with prolonged survival."

The OVATION Study is designed to enroll three to six patients per dose cohort at escalating doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first three cohorts each enrolled three patients. Enrollment in the fourth and final cohort is underway, and Celsion expects to report full data from the OVATION Study by the first quarter of 2017. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin and Doxil.