On February 17, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW), for Engineered anti PD-L1 monoclonal antibody "atezolizumab (genetic recombinant)" for the treatment of "unresectable advanced or recurrent non-small cell lung cancer (NSCLC) (Press release, Chugai, FEB 16, 2017, View Source [SID1234517748])."

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"The cancer immunotherapy has set a new trend of cancer treatment worldwide," said Dr. Yasushi Ito, Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit. "Atezolizumab, an immune checkpoint inhibitor, is the only anti PD-L1 antibody approved in the United States for the treatment of lung cancer. We are committed to deliver atezolizumab to patients as early as possible to contribute to the development of and access to better treatments in Japan."

Chugai filed the application with the MHLW based on the results from a global phase III clinical study (the OAK study) and several clinical studies.

The OAK study is a global, multicenter, open-label, randomized, controlled Phase III study that evaluated the efficacy and safety of atezolizumab compared with docetaxel in people with locally advanced or metastatic NSCLC whose disease had progressed following previous treatment with platinum-containing chemotherapy, with the primary analysis consisting of the first 850 randomized patients. The primary endpoint of this study was overall survival (OS).

The study showed that the median OS was 13.8 months (95% CI: 11.8-15.7 months) for the atezolizumab group and 9.6 months (95% CI: 8.6-11.2 months) for the docetaxel group. The atezolizumab arm showed a statistically significant OS extension, regardless of their levels of PD-L1 expression [HR=0.73 (95% CI: 0.62-0.87), P=0.0003 (stratified log-rank test)].

As for safety, the adverse events (AEs) expressed in both arms in the OAK study were consistent with previous reports. AEs occurring more frequently for atezolizumab arm than docetaxel arm were musculoskeletal pain (10.5% for atezolizumab vs. 4.3% for docetaxel) and pruritus (8.2% for atezolizumab vs. 3.1% for docetaxel).

Please refer to Roche’s press release on October 9, 2016 for the details of the OAK study results.
View Source

In Japan, the annual forecast of a lung cancer prevalence is estimated to be about 134,000 in 2015 (male: 91,000, female: 43,000). The annual mortality of lung cancer is about 77,000 (male: 55,000, female: 22,000, predicted figure at 2015) and lung cancer is the leading cause of cancer deaths in Japan.*

As the top pharmaceutical company in the field of oncology in Japan, Chugai will work for the early approval to provide atezolizumab as a new treatment option for patients with unresectable advanced or recurrent NSCLC and medical professionals.

* Center for Cancer Control and Information Services. Projected Cancer Statistics, 2015 (View Source)

About atezolizumab
Atezolizumab is a monoclonal antibody designed to target a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 binds to PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this coupling, atezolizumab enable the activation of T cells, effectively detect and attack tumour cells.
Atezolizumab (overseas brand name: Tecentriq) is the anti-PD-L1 immune checkpoint inhibitor approved by the FDA, and is indicated for the treatment of locally advanced or metastatic urothelial carcinoma (UC) in May, 2016 and for the treatment of metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy in October, 2016. The FDA granted priority review for atezolizumab for the treatment of locally advanced or metastatic UC who are ineligible for cisplatin chemotherapy.

On February 17, 2017 AstraZeneca reported positive results from its Phase III OLYMPIAD trial comparing Lynparza (olaparib) tablets (300mg twice daily) to physician’s choice of a standard of care chemotherapy in the treatment of patients with HER2-negative metastatic breast cancer harbouring germline BRCA1 or BRCA2 mutations (Press release, AstraZeneca, FEB 16, 2017, View Source [SID1234517746]). Patients treated with Lynparza showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) compared with those who received chemotherapy (capecitabine, vinorelbine or eribulin).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "These results are positive news for patients with BRCA-mutated metastatic breast cancer, a disease with a high unmet need, and are the first positive Phase III data for a PARP inhibitor beyond ovarian cancer. This is highly encouraging for the development of our broad portfolio which aims to treat multiple cancers by targeting DNA damage response pathways."

Initial findings from the OLYMPIAD study indicate that the safety profile of Lynparza was consistent with previous studies.

A full evaluation of the OLYMPIAD data is ongoing and the results will be submitted for presentation at a forthcoming medical meeting. AstraZeneca will be working with regulatory authorities to make Lynparza available to patients with this type of breast cancer.

About Metastatic Breast Cancer
Approximately one in eight women are diagnosed with breast cancer. Of these patients, approximately one-third are either diagnosed with or progress to the metastatic stage of the disease.1 Despite treatment options increasing during the past three decades there is currently no cure for patients diagnosed with metastatic breast cancer. Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving or at least maintaining a patient’s quality of life.

About OLYMPIAD
OLYMPIAD is a randomised, multi-center Phase III trial assessing the efficacy and safety of Lynparza (300 mg twice daily) to ‘physician’s choice’ chemotherapy (capecitabine, vinorelbine, eribulin) in 302 patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are predicted or suspected to be deleterious. The international study was conducted in 19 countries from across Europe, Asia, North America and South America.

The primary endpoint of the trial was progression-free survival (PFS) as measured by a Blinded Independent Central Review (BICR). Secondary endpoints include overall survival (OS), time to second progression or death (PFS2), objective response rate (ORR), and effect on health-related quality of life (HRQoL).

About Germline BRCA mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.2

Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast and ovarian cancers, and they have been associated with increased risks of several additional types of cancer. Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers 3 and about 5 to 10 percent of all breast cancers.4 In addition, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall.5 Breast and ovarian cancers associated with BRCA1 and BRCA2 mutations tend to develop at younger ages than their nonhereditary counterparts.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells.

Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA- test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.

On February 16, 2017 Genocea Biosciences, Inc. (NASDAQ:GNCA), a biopharmaceutical company developing T cell-directed vaccines and immunotherapies, reported corporate highlights and financial results for the fourth quarter and year ended December 31, 2016 (Press release, Genocea Biosciences, FEB 16, 2017, View Source [SID1234517735]). Genocea is developing GEN-003, a therapeutic vaccine candidate for the treatment of genital herpes expected to enter Phase 3 development in 2017, and is applying its unique and proprietary T cell antigen identification platform, ATLAS, to immuno-oncology and cancer vaccine development.

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"We are proud to report on our 2016 achievements, as we made important advances in both our GEN-003 and immuno-oncology programs," said Chip Clark, president and chief executive officer of Genocea. "With the announcements of positive virologic and clinical data for GEN-003 from our ongoing Phase 2b trial, we believe we have confirmed a highly attractive clinical profile for GEN-003, which has the potential to be the first new treatment for patients with genital herpes in more than 20 years. We are encouraged by market research indicating that the GEN-003 clinical profile is attractive to both physicians and payers, and, most importantly, to patients, many of whom are dissatisfied with their current treatment options."

Mr. Clark continued: "In addition to the progress on GEN-003, we announced last fall that we are now focusing our early stage development resources on our immuno-oncology programs. We believe there is a significant opportunity to use our ATLAS platform in immuno-oncology to comprehensively profile T cell responses to cancer. We believe that we can create value by developing novel therapeutic neoantigen cancer vaccines and by developing non-invasive assays to define patient selection for clinical trials and clinical practice. As we presented at our first-ever R&D Day in December, we are making significant progress in both areas and remain on track to file an IND for our first cancer vaccine (GEN-009) by the end of this year."

Program Highlights

GEN-003 Program Milestones

March 2016: Announced positive efficacy data from the Phase 2 dose-optimization trial, demonstrating sustained reductions in the rate of viral shedding and clinical efficacy across secondary clinical endpoints 12 months after dosing
June 2016: Presented detailed 6- and 12-month clinical and viral shedding data from the Phase 2 dose-optimization trial at the American Society for Microbiology annual general meeting, ASM Microbe 2016
September 2016: Announced the first data from the placebo-controlled Phase 2b trial evaluating a new Phase 3-ready formulation, with GEN-003 demonstrating significant reduction in viral shedding immediately after dosing
October 2016: Presented 12-month immunogenicity data from the Phase 2 dose-optimization trial at the Infectious Disease Society of America (IDSA) annual meeting, IDWeek 2016, demonstrating GEN-003 effects clear and robust T and B cell responses
January 2017: Announced positive 6-month results from the Phase 2b clinical trial showing statistical significance vs. placebo for multiple clinical endpoints
Immuno-Oncology Program Milestones

November 2016: Announced new findings supporting the potential of the proprietary ATLAS technology to identify clinically meaningful neoantigens compared to those identified by predictive algorithms and presented the results at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 31st Annual Meeting & Associated Programs, SITC (Free SITC Whitepaper) 2016
December 2016: Announced two immuno-oncology collaborations, Checkmate Pharmaceuticals, Inc. and US Oncology, each employing ATLAS to characterize T cell responses to optimize clinical development and to discover new antigens, respectively
Anticipated Upcoming Milestones and Events

Milestones

1Q 2017: GEN-003 end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) expected; will confirm the design of the GEN-003 Phase 3 program
2H 2017: GEN-003 24-month Phase 2 data expected; will inform likely timing of maintenance dosing for GEN-003
2H 2017: GEN-003 12-month Phase 2b data anticipated; expected to reconfirm clinical profile of GEN-003 at 1 year post dosing
4Q 2017: GEN-003 Phase 3 program start expected
4Q 2017: GEN-009 neoantigen cancer vaccine Investigational New Drug (IND) application filing expected
Events

March 2017: Presentation at the Cowen 37th Annual Health Care Conference in Boston
April 2017: Presentation at the Needham & Company 16th Annual Healthcare Conference in NYC
Financial Guidance

Genocea expects that its existing cash, cash equivalents and investments are sufficient to support its operating expenses and capital expenditure requirements into the first quarter of 2018, without assuming any receipt of proceeds from potential business development partnerships, equity financings or debt drawdowns. This guidance assumes commencing Phase 3 trials for GEN-003 for genital herpes in the fourth quarter of 2017 and filing an IND for GEN-009 for cancer by the end of the year, however it is Genocea’s strategy to secure additional sources of financing in advance of starting GEN-003 Phase 3 clinical trials.

Fourth Quarter and Year-End 2016 Financial Results

Cash Position: Cash, cash equivalents and investments as of December 31, 2016 were $63.4 million compared to $75.5 million as of September 30, 2016.
Research and Development (R&D) Expenses: R&D expenses for the quarter ended December 31, 2016 increased $5.3 million, to $11.8 million, from the same period in 2015, driven by higher manufacturing and clinical costs for GEN-003 together with higher personnel and lab-related costs related to Genocea’s immuno-oncology programs. These increases were partially offset by reduced spending on early stage infectious disease programs.
General and Administrative (G&A) Expenses: G&A expenses for the fourth quarter of 2016 were $3.9 million, compared to $3.8 million for the same period in 2015. The slight increase reflects higher personnel costs to support Genocea’s expanding R&D operations.
Net Loss: Net loss was $16.0 million for the quarter ended December 31, 2016, compared to a net loss of $10.3 million for the same period in 2015.
Full Year 2016 Financial Results

Cash Position: Cash, cash equivalents and investments as of December 31, 2016 were $63.4 million, compared to $106.4 million as of December 31, 2015.
R&D Expenses: R&D expenses for the year ended December 31, 2016 were $34.6 million, compared to $28.0 million for the same period in 2015, reflecting higher personnel costs, consulting and professional services costs, clinical costs, and lab-related costs to support the continued advancement of GEN-003. These increased costs were partially offset by lower GEN-003 manufacturing costs in 2016 compared to 2015. Increases in personnel and lab related costs across early stage research programs were offset by a reduction in GEN-004 costs for which a clinical trial was completed in late 2015 and further development of this program was suspended.
G&A Expenses: G&A expenses were $15.4 million for the year ended December 31, 2016, compared to $14.0 million for the same period in 2015, reflecting an increase in market research costs to support GEN-003 and higher depreciation costs from facility expansion in late 2015.
Refund of Research and Development Expense: A gain of $1.6 million for the quarter ended March 31, 2016 resulted from cash received pursuant to contractual obligations under a collaboration agreement with Isconova AB ("Isconova") (since acquired by Novavax, Inc.) to refund R&D expenses paid by Genocea to Isconova between 2009 and 2011 relating to the development of the Matrix-M adjuvant technology.
Net Loss: Net loss was $49.6 million for the year ended December 31, 2016, compared to a net loss of $42.5 million for the same period in 2015.