On August 11, 2016 Checkpoint Therapeutics, Inc. ("Checkpoint"), a Fortress Biotech (NASDAQ:FBIO) company, reported that its Investigational New Drug ("IND") application for CK-101, its novel, oral, third generation EGFR inhibitor product candidate, has been accepted by the U.S. Food and Drug Administration ("FDA") and is now active (Press release, Fortress Biotech, AUG 11, 2016, View Source [SID:1234514509]). The IND acceptance enables Checkpoint to begin a Phase 1/2 clinical trial of CK-101. The trial, expected to begin in September, is designed to assess the safety, tolerability and efficacy of CK-101 in EGFR T790M mutation-positive non-small cell lung cancer patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The acceptance of this IND marks an important milestone for Checkpoint and the CK-101 program," said James F. Oliviero, III, President and CEO of Checkpoint Therapeutics. "We look forward to commencing clinical trials for CK-101, which we plan to develop as both a monotherapy and in combination with our portfolio of immuno-oncology agents."

Checkpoint holds an exclusive worldwide license (except with respect to certain Asian countries) to CK-101 (also known as RX518), which it acquired from NeuPharma, Inc. in 2015.

About Checkpoint Therapeutics
Checkpoint Therapeutics, Inc. ("Checkpoint"), a Fortress Biotech company, is an innovative, immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel, non-chemotherapy, immune-enhanced combination treatments for patients with solid tumor cancers. Checkpoint aims to acquire rights to these technologies by licensing the rights or otherwise acquiring an ownership interest in the technologies, funding their research and development and eventually either out-licensing or bringing the technologies to market. Currently, Checkpoint is developing a portfolio of fully human immuno-oncology targeted antibodies generated in the laboratory of Dr. Wayne Marasco, MD, PhD, a professor in the Department of Cancer Immunology and AIDS at the Dana-Farber Cancer Institute. The portfolio of antibodies Checkpoint licensed from Dana-Farber includes antibodies targeting Programmed death-ligand 1 ("PD-L1"), Glucocorticoid-induced TNFR related protein ("GITR") and carbonic anhydrase IX ("CAIX"). Checkpoint plans to develop these novel immuno-oncology and checkpoint inhibitor antibodies on their own and in combination with each other, as data suggests that combinations of these targets may work synergistically together. Checkpoint has also licensed and is developing three oral, small molecule, targeted anti-cancer agents, consisting of an inhibitor of epidermal growth factor receptor ("EGFR") mutations, an inhibitor of the bromodomain and extra-terminal ("BET") protein, BRD4, and an inhibitor of poly (ADP-ribose) polymerase ("PARP"). Checkpoint will also seek to add additional immuno-oncology drugs and other targeted therapies in order to create wholly-owned proprietary combinations that leverage the immune system and complimentary mechanisms. Checkpoint is headquartered in New York City. For more information, visit www.checkpointtx.com.

On August 11, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that its Phase 2 "window of opportunity" clinical study of its lead immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with late-stage HPV-associated oropharyngeal cancer (HPVOPC) met its stage 1 primary objective and is advancing into the second stage of the clinical study (Press release, Advaxis, AUG 11, 2016, View Source [SID:1234514508]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This is an investigator-initiated prospective clinical study of patients with stage I-IV HPVOPC who are to undergo ablative trans-oral robotic surgery (TORS) as a preoperative treatment. The clinical study leverages the five- to six-week period between diagnosis and TORS, making it possible to analyze and compare the tumor microenvironment as well as peripheral blood samples collected before and after AXAL treatments.

The clinical study is designed to show that AXAL is highly immunogenic and worth further investigation if the overall rate of vaccine-induced T-cell responses is 75 percent or more. By looking at both IFN-γ and TNFα expressing T cells in the peripheral blood, it was found that systemic HPV-reactive T-cell responses were increased in enough patients treated with AXAL to meet the stage 1 immune response target. This evidence of systemic response is consistent with a recent abstract presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) describing increased cytotoxic T-cell infiltration into the tumor microenvironment in HPVOPC patients treated with AXAL.

"The assessment of the TNFα and IFN-γ response based on data from eight of the anticipated nine patients to be enrolled in stage 1 confirmed that the clinical study has already met the target for the overall rate of vaccine-induced T-cell response, paving the way for us to progress to stage 2," said the study’s lead investigator Andrew G. Sikora, MD, PhD, of the Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery at Baylor College of Medicine. "Together with our prior published data showing increased intratumoral T-cell infiltration in a significant number of AXAL treated patients, these data provide the confidence needed to move forward with the definitive evaluation of its immunogenicity."

Stage 2 of the clinical study will enroll up to 13 patients with late-stage HPVOPC. This stage of the clinical study will be conducted at the Icahn School of Medicine at Mount Sinai and a second investigative site anticipated to be the Baylor College of Medicine. The study received a three-year $1.1 million grant from the U.S. Food and Drug Administration’s Office of Orphan Products Development, which funds research for the development of products for rare diseases.

HPV-Associated Head and Neck Cancers

More than 90 percent of head and neck squamous cell oropharyngeal cancers originate from the mucosal linings of the oral cavity, pharynx or larynx. Currently, 60 to 80 percent of these cancers are caused by HPV. Head and neck cancers are treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow.

The incidence of HPV-associated head and neck cancers has been increasing at an epidemic rate, while head and neck cancers from other causes have been decreasing. According to the World Health Organization, approximately 15 to 20 percent of the 400,000 new cases of head and neck cancer are HPV-related. In the US, there are about 12,000 new cases of HPV-associated head and neck cancer per year and it affects men about 3 times more frequently than women. HPV-associated head and neck cancer is growing fastest in developed countries like the U.S.

About Axalimogene Filolisbac

AXAL is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. AXAL has Orphan Drug Designation in the U.S. for the treatment of these three indications. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.

On August 11, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported that the first patient has been dosed in the Company’s global phase 2 study evaluating tazemetostat, a first-in-class EZH2 inhibitor, for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function (Press release, Epizyme, AUG 11, 2016, View Source [SID:1234514505]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Mesothelioma remains a cancer that is very difficult to treat and has an extremely poor prognosis," said Marjorie Zauderer, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center. "The overwhelming majority of patients are refractory to or relapse following first-line treatment with chemotherapy leaving them with no approved treatment options. The preclinical data demonstrating that EZH2 inhibition may play a role in the treatment of mesothelioma is promising, and I look forward to exploring the potential for tazemetostat as a targeted agent for patients with this devastating disease."

Mesothelioma affects nearly 12,000 people each year in major markets, of which 40 to 60% have tumors characterized by BAP1 loss-of-function. The median overall survival for all patients with mesothelioma generally ranges from eight to 14 months from the time of diagnosis. The most commonly used first-line treatment consists of cisplatin or carboplatin combined with pemetrexed, which is the only drug approved (2004) for the treatment of mesothelioma1.

"Patient dosing in this phase 2 study marks another milestone for Epizyme and the expansion of our clinical development program into a new cancer indication for which there is a significant medical need," said Peter Ho, M.D., Ph.D., Executive Vice President and Chief Medical Officer, Epizyme. "With this study, Epizyme now has four registration-supporting monotherapy trials underway with tazemetostat, and plans for two combination trials to be initiated later this year."

Phase 2 Study Design
The international, open-label, phase 2 study will evaluate tazemetostat as a monotherapy in a total of 67 patients at multiple sites in the United States, United Kingdom and France. Tazemetostat is orally administered at a dose of 800 mg twice-daily. The safety and pharmacokinetic profile of tazemetostat will first be evaluated in 12 patients with relapsed or refractory mesothelioma regardless of BAP1 status. Subsequently, a total of 55 patients with relapsed or refractory mesothelioma characterized by BAP1 loss-of-function will be treated using a two-stage study design. The primary endpoint of the study is disease control rate (complete response, partial response or stable disease) at 12 weeks. Secondary endpoints include overall response rate, progression-free survival, duration of response and overall survival.

EZH2 Inhibition in Mesothelioma
Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary drug development platform. Aberrant EZH2 activity results in misregulation of genes that control cell proliferation and has been associated with a diverse set of human cancers. Preclinical findings from published reports suggest that mesothelioma, and particularly mesothelioma characterized by BAP1 loss of function, may be sensitive to EZH2 inhibition2. Mesothelioma characterized by BAP1 loss of function accounts for 40 to 60 percent of the approximately 12,000 new mesothelioma cases each year in major markets3-6.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing phase 2 programs in non-Hodgkin lymphoma (NHL), certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma, and mesothelioma.

The company plans to initiate additional clinical trials of tazemetostat in 2016, including a combination with R-CHOP in collaboration with the Lymphoma Study Association and a combination with Tecentriq (atezolizumab) in collaboration with Genentech, a member of the Roche Group, both in patients with diffuse large B-cell lymphoma.