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6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

On July 7, 2014 Compugen reported that it has achieved the initial milestone in the cancer immunotherapy collaboration it entered last year with Bayer HealthCare (Bayer) (Filing 6-K , Compugen, JUL 7, 2014, View Source [SID:1234500619]). The collaboration provides for the development and commercialization of therapeutic antibodies against two checkpoint protein candidates discovered by Compugen. The milestone being announced today relates to the first preclinical milestone for one of two checkpoint protein candidates for which Compugen will receive a $1.2 million payment out of the $30 million potential milestone payments associated with joint preclinical research for the two programs.

Dr. Anat Cohen Dayag, Compugen’s President and CEO, stated, “We are very pleased by the achievement of this initial drug development milestone for one of the two programs in our collaboration with Bayer. After investing more than a decade of extensive multidisciplinary research in establishing our broadly applicable predictive discovery infrastructure, we selected the area of checkpoint-based cancer immunotherapy as our first focused discovery effort. Therefore, it is extremely satisfying to see our growing competitive position, in terms of both advancement of our therapeutic programs in immuno-oncology and continuing discoveries of novel targets in this exciting area, which is increasingly being viewed as a potential major breakthrough in cancer treatment.”

About the Bayer HealthCare/Compugen Collaboration and License Agreement
The collaboration and license agreement provides the framework for the research, development, and commercialization of antibody-based therapeutics for cancer immunotherapy against two novel Compugen-discovered immune checkpoint regulators. Under the terms of the agreement, Bayer and Compugen are jointly pursuing a preclinical research program for each of the two candidates. Subsequently, Bayer will have full control over further development and have worldwide commercialization rights for potential cancer therapeutics.

Under the terms of the agreement, Compugen has received an upfront payment of $10 million and is eligible to receive over $500 million in potential milestone payments for both checkpoint programs, plus an additional $30 million of potential milestone payments associated with joint preclinical research for the two programs. Compugen is also eligible to receive royalties on global net sales from any resulting products under the collaboration.

Novartis personalized cell therapy CTL019 receives FDA Breakthrough Therapy designation

On July 7, 2014 Novartis reported that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy status to CTL019, an investigational chimeric antigen receptor (CAR) therapy for the treatment of pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (Press release Novartis, JUL 7, 2014, View Source [SID:1234500616]). The Breakthrough Therapy filing was submitted by the University of Pennsylvania’s Perelman School of Medicine (Penn) which has an exclusive global agreement with Novartis to research, develop and commercialize personalized CAR T cell therapies for the treatment of cancers.

This is the fifth Breakthrough Therapy designation for Novartis, continuing the company’s trajectory as a leader in developing innovative therapies to help treat diseases in which there remains significant unmet medical need. Novartis’ Zykadia(TM) (ceritinib, previously known as LDK378), for the treatment of anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC), is one of the first medicines to receive an FDA approval following earlier receipt of Breakthrough Therapy designation by the FDA.

"This Breakthrough Therapy designation underscores the potential of CTL019 as a life-saving therapy for patients with relapsed/refractory ALL, who are in desperate need of new treatment options," said David Epstein, Division Head, Novartis Pharmaceuticals. "Novartis welcomes increased dialogue with the FDA and a potentially expedited review to streamline the development of CTL019 and hopefully bring this promising therapy to patients as quickly as possible."

According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. The designation includes all of the fast track program features, as well as more intensive FDA guidance. It is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.

"This is a major milestone as we are now one step closer in helping address the high unmet needs of this patient population," said Carl H. June, M.D., Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center of the University of Pennsylvania. "We are excited about the strength of the positive early data seen in pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia and look forward to building upon these findings as we continue advancing the CTL019 clinical program in Phase II trials."

Novartis recently established the Cell and Gene Therapies Unit under the leadership of Usman Azam, Global Head, to bring an intense focus on advancing innovative cell-based therapies, including the development of CARs. Novartis holds the worldwide rights to CARs developed through the collaboration with Penn for all cancer indications, including the lead program, CTL019.

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Nexavar® (sorafenib tablets) now Approved in Canada for the Treatment of Differentiated Thyroid Cancer

On July, 7, 2014 Bayer reported that the Health Canada approval of Nexavar for the treatment of patients with locally advanced or metastatic, progressive, differentiated thyroid carcinoma (DTC), refractory to radioactive iodine (RAI) (Press release Bayer, JUL 7, 2014, View Source [SID:1234500615]).

The approval is based on data from the Phase III DECISION (stuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine refractory thyrOid caNcer) trial. In the trial, sorafenib significantly extended progression-free survival (PFS), the primary endpoint of the study, compared to placebo (HR=0.59 [95% CI, 0.45-0.76]; p<0.0001), which represents a 41 percent reduction in the risk of disease progression or death for patients who received sorafenib compared to placebo-treated patients. The median PFS was 10.8 months in patients treated with sorafenib, compared to 5.8 months in patients receiving placebo. The safety and tolerability profile of sorafenib in patients in the trial was generally consistent with the known profile of sorafenib. The most common treatment-emergent adverse events in the sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, weight loss, fatigue, hypertension and rash. Results from the trial were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2013 and published in The Lancet in April 2014.

Human Anti-human PD-1 Monoclonal Antibody "OPDIVO® Intravenous Infusion 20 mg/100 mg" Receives Manufacturing and Marketing Approval in Japan for the Treatment of Unresectable Melanoma

On July 4, 2014 Ono Pharmaceutical reported that it had received manufacturing and marketing approval for the human anti-human PD-1 monoclonal antibody "OPDIVO Intravenous Infusion 20 mg/100 mg"("OPDIVO") for the treatment of unresectable melanoma (Press release Ono, JUL 4, 2014, View Source [SID:1234500642]).

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Melanoma is considered to be a form of tumor characterized by the malignant transformation of pigment-producing cells located in the skin. In Japan, there has been an unmet need for an effective treatment for patients with surgically unresectable melanoma, who have an extremely poor prognosis that no treatment exists to significantly improve.

OPDIVO is a human anti-human PD-1 monoclonal antibody. PD-1 (programmed death-1), a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body (negative signal). Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. OPDIVO is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. OPDIVO is the world’s first approved drug targeting PD-1.

"We are delighted to obtain a manufacturing and marketing approval as a drug targeting PD-1, which receives a lot of attention in tumor immunity, for the first time in the world." said Gyo Sagara, the President and Representative Director of ONO. "ONO would like to obtain approvals for additional indications on ongoing development for other cancers to bring many patients OPDIVO as soon as possible."

Accumulating further clinical data is important in ensuring that OPDIVO will be used more safely and effectively. ONO is committed to taking actions necessary for the proper use of OPDIVO by implementing a post-marketing use-results survey (all-case surveillance) and collecting clinical data on the safety and efficacy of OPDIVO pursuant to the conditions for its approval.

Because of the very limited number of patients treated with OPDIVO in Japanese clinical trials, ONO is required to perform a post-marketing use-results survey covering all cases until data on a certain minimum number of patients have been accumulated. Through these activities, ONO should identify the characteristics of patients to be treated with OPDIVO and collect safety and efficacy data as soon as possible, thereby taking actions necessary to ensure the proper use of OPDIVO

Japan becomes first country to approve Roche's alectinib for people with a specific form of advanced lung cancer

On July 4, 2014 Roche reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved alectinib for the treatment of people living with non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase fusion gene-positive (ALK+) (Press release Hoffmann-La Roche, JUL 4, 2014, View Source [SID:1234500613]). The approval was based on results from a Japanese Phase I/II clinical study (AF-001JP) for people whose tumors were advanced, recurrent or could not be removed completely through surgery (unresectable).

“The approval of alectinib, a treatment specifically targeted to ALK+ lung cancer, in Japan is great news for people living with this difficult to treat disease,” said Sandra Horning MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Another interesting aspect of alectinib is that based on early studies it may also work in people living with tumors that have spread to the brain, a difficult area to reach with current medicines. Our research will continue in this area.”

Alectinib is expected to be made available in Japan later this year. Alectinib was also granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) in June 2013 for patients with ALK+ NSCLC who progressed on crizotinib. BTD is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

Global pivotal studies are currently ongoing which will further inform on the clinical value of alectinib in this disease setting as well as in treatment-naïve patients. The results of these studies will be used in future regulatory submissions in the US and in Europe.

About the Japanese Phase I/II study (AF-001JP)
This trial was conducted in 13 medical institutions in ALK fusion gene positive recurrent or advanced non-small cell lung cancer patients with a treatment history of one or more chemotherapy regimens.

The trial consisted of two phases: Phase I that evaluated safety, tolerability, pharmacokinetic parameters and recommended dose (24 patients), and a Phase II part that evaluated the efficacy and safety of the recommended dose (46 patients). The primary endpoint was response rate.

Japanese Phase I/II study (AF-001JP) results
The Phase I part of the study determined a recommended dose of 300 mg twice daily. No dose limiting toxicity was observed.

The Phase II portion of the study was conducted using the recommended dose, and demonstrated a response rate of 93.5% (43/46 patients; 95%CI: 82.1-98.6%).
– 14 patients entered the study with Central Nervous System (CNS) metastases1
– 9 of the 14 patients remained in the study without CNS or systemic progression for more than 12 months1
Progression Free Survival (PFS) at 12 months was measured as 83% (95% CI: 68-92%)1
There were no treatment-related deaths and/or grade 4 or higher serious adverse reactions assessed according to CTCAE (Common Terminology Criteria for Adverse Events) defined by the Japan Clinical Oncology Group. The most frequently observed grade 3 or higher adverse reaction was neutropenia, and the incidence of the adverse event was 4 out of 58 patients (6.9%) who were treated with 300 mg twice daily, the approved dose