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Selexis SA Enters into Commercial Cell Line License Agreement with Pieris Pharmaceuticals for Immuno-Oncology Bispecific Drug Candidate

On September 7, 2016 Selexis SA, a pioneering life sciences company and a global leader in mammalian (suspension-adapted CHO-K1) cell line generation, reported the signing of a license agreement that provides Pieris Pharmaceuticals with access to Selexis SUREtechnology Platform and SURE CHO-M Cell Line to advance the development of PRS-343, Pieris’ lead bispecific immuno-oncology drug candidate (Press release, Selexis, SEP 7, 2016, View Source [SID:1234514986]). PRS-343 is a CD137/HER2 bispecific that is designed to promote CD137 clustering by bridging CD137-positive T cells with HER2-positive tumor cells, thereby providing a potent costimulatory signal to tumor antigen-specific T cells.

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"Through the innovation behind Selexis’ technology, our dedicated researchers are driven to provide companies such as Pieris with high performance, cost-effective solutions for development of their own innovative biological drug candidates," said Marco Bocci, PhD, DPharm, Selexis vice president, licensing and business development. "Earlier this year, Pieris announced encouraging in vivo proof of concept data for PRS-343, a bispecific protein produced with the Selexis SUREtechnology Platform and cell line that is expected to enter the clinic in the first half of 2017. We look forward to the continued progression of this important and unique drug candidate."

Selexis’ proprietary SUREtechnology Platform facilitates the rapid, stable, and cost-effective production of virtually any recombinant protein and provides seamless integration of the biologics development continuum, spanning discovery to commercialization.

The Selexis SURE CHO-M Cell Line is a proprietary high-performance mammalian cell line that is derived from CHO-K1 cells and used for the production of therapeutic recombinant proteins and monoclonal antibodies (mAbs). The growth and production properties of the Selexis SURE CHO-M Cell Line are well defined, and the feed strategy has been optimized, allowing for faster and more efficient scale-up to bioreactors. Therapeutics that are generated using Selexis SURE CHO-M cells are in both clinical trials and marketed products.

Propanc Files Application for Orphan Medicinal Product Designation in the EU for Pancreatic Cancer

On September 7, 2016 Propanc Health Group Corporation (OTCQB: PPCH) ("Propanc" or "the Company"), an emerging healthcare company focusing on development of new and proprietary treatments for cancer patients suffering from solid tumors such as pancreatic, ovarian and colorectal cancers, reported it has submitted an application for Orphan Medicinal Product Designation (OMPD) to the European Medicines Agency (EMA) for PRP, a solution for intravenous administration of pancreatic proenzymes trypsinogen and chymotrypsinogen (Press release, Propanc, SEP 7, 2016, View Source [SID:1234514985]). The proposed orphan drug indication for PRP is for the treatment of pancreatic cancer, responsible for 338,000 cancer diagnoses and 331,000 deaths worldwide in 2012, and a major unmet medical issue.

"This is a critical step for Propanc and its plans for developing PRP as a treatment solution for aggressive, fast spreading solid tumors. Pancreatic cancer is an area where there is an urgent need for viable solutions and we remain determined to bring to market what could become a targeted and safer treatment approach, which we hope will meaningfully extend patient lives," said James Nathanielsz, Propanc’s Chief Executive Officer. "We will work hard with the authorities to provide a strong rationale for why PRP qualifies for orphan medicinal product designation, which will provide exciting potential benefits to fast track the development process and provide attractive benefits for up to ten years when we achieve market approval."

The European Union (EU) grants Orphan Medicinal Product Designation (OMPD) status to products which treat rare diseases, providing a range of incentives to sponsors developing drugs or biologics. To stimulate the research and development of orphan drugs, in 2000, the EU introduced new legislation with the aim of providing incentives for the development of orphan and other medicinal products for rare disorders. Today, companies with an orphan designation for a medicinal product benefit from incentives such as fee waivers, a 10 year market exclusivity period post authorization for designated products; scientific assistance for marketing authorizations, and the possibility of a Community marketing authorization. The EMA grants OMPD to products that meet one of the following designation criteria:

the life-threatening or debilitating nature of the condition;
the medical plausibility of the proposed orphan indication;
that the prevalence of the condition in the European Union is not more than five in 10,000; or that it is unlikely that marketing the medicinal product in the European Union, without incentives, would generate sufficient return to justify the necessary investment;
that no satisfactory method of diagnosis prevention or treatment exists, or if such a method exists, that the medicinal product will be of significant benefit to those affected by the condition.
The rationale for developing PRP, a formulation of the pancreatic proenzymes trypsinogen and chymotrypsinogen for intravenous administration, in the proposed indication pancreatic cancer, is based on a set of in-vitro studies on cancer stem cells generated from pancreatic cancer cell lines as well as xenograft and syngeneic mouse models of pancreatic cancer. In summary, these data indicate that the dramatic reduction of cellular markers associated with the process of epithelial-mesenchymal transition (EMT) as a consequence of PRP treatment could not only reverse the EMT process with the implication to stop tumor progression and metastasis, but also seem to suppress the development of cancer stem cells (CSCs). Consequently, these results are strong indicators of the therapeutic potential of PRP that could be categorized as an anti-CSC therapeutic drug.

Preliminary early clinical data on the treatment of four patients with pancreatic cancer have been obtained with a rectal formulation of pancreatic proenzymes trypsinogen and chymotrypsinogen in the context of a UK "Specials" License treatment, administered by Dr Julian Kenyon, at the Dove Clinic Center for Integrated Medicine, back in the mid 2000’s. Together, these data support the medical plausibility of the proposed indication and a distinctive benefit-safety profile of PRP for the treatment of pancreatic cancer.

FDA Accepts Supplemental Biologics License Application, Assigns Priority Review and Grants Breakthrough Therapy Designation to Merck’s KEYTRUDA® (pembrolizumab) for First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer

On September 7, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors express PD-L1, with a PDUFA, or target action, date of Dec. 24, 2016 (Press release, Merck & Co, SEP 7, 2016, View Source [SID:1234514983]). Additionally, the FDA granted Breakthrough Therapy Designation for this indication. Merck has also submitted a Marketing Authorization Application to the European Medicines Agency for this indication.

The submissions were based on data from the pivotal phase 3 KEYNOTE-024 study, which showed that KEYTRUDA monotherapy resulted in superior progression-free survival (PFS) as well as overall survival (OS) compared with standard chemotherapy in patients with advanced NSCLC whose tumors expressed high levels of PD-L1 (tumor proportion score of 50 percent or more). Based on the results, the trial was stopped early to give patients still on chemotherapy the opportunity to receive KEYTRUDA. Merck filed for approval of KEYTRUDA in the first-line setting at a dose of 200 mg every three weeks, the dose studied in KEYNOTE-024.

"Chemotherapy has been the foundation of first-line treatment for non-small cell lung cancer for decades, so the significant improvement in survival in patients with high PD-L1 expression seen with KEYTRUDA compared to chemotherapy is welcome news," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We appreciate the opportunity to work with regulatory authorities to make KEYTRUDA a first-line treatment option in non-small cell lung cancer."

The FDA’s Breakthrough Therapy Designation is intended to expedite the availability of promising new therapies that are planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates substantial improvement over existing therapies on one or more clinically significant endpoints. Merck previously announced that KEYTRUDA (pembrolizumab) was granted breakthrough status for specific patients with advanced melanoma, metastatic NSCLC in previously treated patients, microsatellite instability high metastatic colorectal cancer, and relapsed or refractory classical Hodgkin Lymphoma.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks.

Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy, at a dose of 2 mg/kg every three weeks. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab). This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. An sBLA is currently under review with the FDA for full approval of the existing second-line NSCLC indication. The application is based on data from KEYNOTE-010, a pivotal phase 2/3 confirmatory trial which demonstrated improved survival with KEYTRUDA compared to standard chemotherapy in previously treated patients with advanced NSCLC who had PD-L1 expression on one percent or more of the cancer cells. The FDA target action date is Oct. 24, 2016.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy at a fixed dose of 200 mg every three weeks. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and occurred more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA (pembrolizumab).

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 330 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

8-K – Current report

On September 7, 2016 Epizyme, Inc. (the "Company") reported that the Independent Data Monitoring Committee (the "IDMC") convened on September 6, 2016 to assess the futility of tazemetostat in the follicular lymphoma with wild-type EZH2 cohort of the Company’s ongoing phase 2 study in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) (Filing, 8-K, Epizyme, SEP 7, 2016, View Source [SID:1234514982]). Based on review of the clinical experience to date, the IDMC has confirmed that the study cohort has surpassed its pre-specified futility hurdle, and the Company will continue to accrue patients to fully enroll this cohort. Multiple objective responses have been observed in this cohort of patients, including complete and partial responses, as well as stable disease in patients still on study beyond the first ten evaluated for futility. In addition, there were no safety concerns raised by the IDMC in their review of the study.

All five study cohorts have now surpassed their pre-specified futility hurdles, and enrollment continues in all study arms. The Company plans to present mature data from all five study cohorts in the first half of 2017, consistent with prior guidance.

DelMar Pharmaceuticals and Accurexa to Collaborate in the Development of a Novel Combination Chemotherapy for the Local Treatment of Brain Cancer

On September 7, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar"), a company focused on developing and commercializing proven cancer therapies in new orphan drug indications, and Accurexa Inc. (OTCQB: ACXA) ("Accurexa"), a company focused on the development of novel neurological therapies to be directly delivered into the brain, reported a collaboration to develop a novel formulation for the local delivery of combination chemotherapy for the treatment of brain cancer and other solid tumors (Press release, DelMar Pharmaceuticals, SEP 7, 2016, View Source [SID:1234514981]).

Under the terms of the collaboration agreement DelMar will supply VAL-083 (dianhydrogalactitol) to be formulated within Accurexa’s proprietary ACX-31 implantable polymer wafer to locally deliver VAL-083 in combination with temozolomide and/or BCNU for the treatment of brain cancer. DelMar has been granted an exclusive option to license or acquire and commercialize product candidates and intellectual property resulting from the research.

DelMar will host a teleconference for shareholders and investors on Wednesday, September 7, 2016 at 5PM EDT. Interested parties can access the call by dialing toll free 1-800-862-9098 or via the internet at: https://engage.vevent.com/rt/delmar_ao~73915172

Mr. Bacha and DelMar management will discuss the Accurexa collaboration and outline the Company’s plans for the remainder of 2016, including steps to advance VAL-083 into a pivotal Phase III and two additional Phase II clinical trials for the treatment of refractory glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer.

Accurexa’s ACX-31 program has been developed in collaboration with Prof. Henry Brem who built one of the largest brain tumor research and treatment centers in the world at Johns Hopkins University and Prof. Robert Langer, who is the David H. Koch Institute Professor at MIT and the most cited engineer in history. Professor Avi Domb at the Hebrew University of Jerusalem will lead the formulation development efforts for the collaboration. Prof. Brem, Prof. Langer and Prof. Domb are pioneers in the development of local drug delivery treatments, and invented and developed Gliadel (carmustine implant) which is a FDA approved, local chemotherapy for the treatment of GBM. Drs. Brem and Langer will serve as advisors for the collaboration.

"Working together with Accurexa will allow DelMar to explore a promising new product opportunity that is complementary to our existing portfolio of systemic drug development programs established around VAL-083 without significant cash outlay or impact on our near-term cash burn rate," said Jeffrey Bacha, Chairman and CEO of DelMar Pharmaceuticals. "This research collaboration will take advantage of our knowledge regarding the unique cytotoxic mechanism of VAL-083 to deliver combination chemotherapy directly to patients’ cancer. Combining drugs with distinct mechanisms for local delivery provides an opportunity to overcome chemoresistance while minimizing potential systemic toxicity."

"We are very pleased to collaborate with DelMar’s experienced team allowing us to leverage their strong development capabilities. They have recently completed a Phase I/II clinical trial of VAL-083 in brain cancer patients and had a successful end-of-Phase II meeting with the FDA while we recently had a positive pre-IND meeting with the FDA for our ACX-31 wafer program. Looking forward to the future development pathway, we believe that the local delivery of VAL-083 as a component of our ACX-31 wafer could potentially provide a new and exciting treatment option for brain cancer patients," said George Yu, MD, Accurexa’s President & CEO.

DelMar and Accurexa believe that combining VAL-083 with temozolomide and/or BCNU within Accurexa’s proprietary drug delivery system may provide treatment advantages while limiting systemic toxicity.

VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in the U.S. for the treatment of gliomas, medulloblastoma and ovarian cancer as well as in Europe for the treatment of glioma.

VAL-083 exhibits its anti-tumor affect by forming DNA cross-links at the N7 position of guanine whereas temozolomide and BCNU primarily target the O6 position of guanine as their site of anti-cancer function.

VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to chemotherapies targeting the O6 position of guanine. DelMar has also demonstrated that the combination of VAL-083 and temozolomide was highly effective against brain tumor stem cells in vitro.

DelMar and Accurexa will seek to establish a novel formulation which incorporates VAL-083 into the ACX-31 polymer wafer and to establish non-clinical proof of concept regarding the proposed advantages of the combination therapy. DelMar will supply Accurexa with VAL-083 and the companies will share certain limited costs associated with the research. DelMar has been granted an exclusive option to license or acquire and commercialize product candidates and intellectual property resulting from the research for a defined period after the completion of the research. DelMar’s option to negotiate a license or acquire the technology includes any and all results, research materials, related information and product candidates, including without limitation ACX-31 and related intellectual property and all rights thereto on an exclusive world-wide basis or other such terms as the parties may agree, in order to further develop and commercialize products based on the research project.

"Both of our companies have already made significant investments into the IP, mechanism of action and formulation of VAL-083 and ACX-31, respectively. Therefore, developing a combined formulation is not expected to require significant cash expenditures. This collaboration is a highly cost-effective approach to expand our product development portfolio by leveraging our companies’ respective capabilities and assets," stated Mr. Bacha.