On October 31, 2016 Selecta Biosciences, Inc. (NASDAQ:SELB), a clinical-stage biopharmaceutical company developing a novel class of targeted antigen-specific immune therapies, reported that results from preclinical studies involving SVP-Rapamycin, the company’s novel immunotherapeutic, were presented by its collaborators Ira Pastan, MD, Chief of the Laboratory of Molecular Biology, and Ronit Mazor, Ph.D., Postdoctoral Fellow at Center for Cancer Research at the National Cancer Institute (NCI), part of the National Institutes of Health (Press release, Selecta Biosciences, OCT 31, 2016, View Source [SID1234516120]).

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Through a collaboration under a Cooperative Research and Development Agreement (CRADA) between Selecta and NCI, the results were obtained by co-administration of SVP-Rapamycin with an investigational anti-cancer therapeutic, LMB-100. LMB-100 is a next-generation recombinant immunotoxin (rIT) developed in the Pastan Lab that is currently undergoing Phase 1 clinical trials at the NIH Clinical Center in patients with mesothelioma and pancreatic cancer.

Dr. Pastan’s presentation at the Immunogenicity and Bioassay Summit 2016 in Baltimore, Maryland was entitled, "Strategies to Reduce Immune Response to Immunotoxins," and Dr. Mazor’s presentation was entitled, "Induction of Tolerance to Immunotoxins Using Nanoparticle Delivery of Rapamycin." Further, Dr. Mazor presented a poster with the title "Nanoparticle-Encapsulated Rapamycin Prevents Primary and Secondary Immune Responses in Murine Models."

LMB-100 is a next-generation immunotoxin comprised of a mesothelin-targeting antibody fragment linked to an engineered cytotoxic domain of Pseudomonas exotoxin A. The majority of mesothelioma patients treated with an earlier version of LMB-100, called SS1P, experienced dose-limiting immune responses despite the use of potent immunosuppressants. However, the few patients tolerating more than one treatment cycle in this trial showed marked antitumor activity in patients with chemotherapy-refractory mesothelioma.

The co-administration of SVP-Rapamycin with LMB-100 in mice models prevented the formation of anti-LMB-100 antibodies and allowed for the administration of at least four treatment cycles, representing a marked increase in the number of effective doses that could be administrated without the onset of neutralizing antibodies. Further, in a tumor model, the addition of SVP-Rapamycin restored the beneficial effect of LMB-100 on controlling tumor growth.

"These pre-clinical proof of concept data clearly demonstrate the potential benefit of co-administrating LMB-100 and SVP-Rapamycin, two products currently used in clinical trials," said Peter Keller, M.Sc., Chief Business Officer at Selecta. "The program is part of our objective to extend our clinical pipeline by applying our SVP technology platform to oncology treatments. In oncology, the effectiveness of many therapies could be enhanced by antigen-specific mitigation of undesired immune responses."

Selecta is developing SVP-Rapamycin for co-administration with biologic therapies for the antigen-specific mitigation of undesired humoral and cellular immune responses. The company is focused on three strategic areas: enzyme therapy, gene therapy and oncology. SVP-Rapamycin has the potential to be co-administered with a multitude of biologic drugs that have been identified in each of these areas to increase the number of treatable patients and/or enhance efficacy and safety.

Selecta’s lead product candidate, SEL-212, applies SVP-Rapamycin to pegsiticase, a pegylated uricase. SEL-212 is designed to be the first non-immunogenic version of uricase, an immunogenic enzyme that targets uric acid. SEL-212 is in a Phase 2 clinical trial and is being developed for patients with chronic refractory and tophaceous gout.

About LMB-100

LMB-100 is a next generation immunotoxin comprised of a mesothelin-targeting antibody fragment linked to an engineered cytotoxic domain of Pseudomonas exotoxin A. Mesothelin, a cell surface antigen discovered in Ira Pastan’s laboratory at NCI, is overexpressed in mesothelioma, pancreatic, ovarian and lung cancers. Dr. Pastan is a world-renowned expert in the design and development of immunotoxins. A first generation mesothelin-targeted immunotoxin, SS1P, could only be given for 1 cycle because it was immunogenic, but showed marked antitumor activity in patients with chemotherapy-refractory mesothelioma, when combined with drugs to suppress the development of anti-drug antibodies. LMB-100 was engineered to reduce immunogenicity and off target toxicity. LMB-100 is currently in phase 1 clinical studies by CCR investigators at the NIH Clinical Center in Bethesda, Maryland.

On October 31, 2016 Novogen Ltd (ASX: NRT; NASDAQ: NVGN) reported that it has entered into a worldwide licensing agreement with Genentech, a member of the Roche Group, to develop and commercialise GDC-0084, a small molecule inhibitor of the phosphoinositide-3-kinase (PI3K) pathway (Press release, Novogen, OCT 31, 2016, View Source [SID1234516119]).

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The lead indication for GDC – 0084 is glioblastoma multiforme (GBM), which is the most aggressive form of brain cancer, accounting for approximately 15% of primary brain tumours. Median overal l survival is considered to be approximately 12 – 15 months from the time of diagnosis. 1 Therapies targeting the PI3K pathway have been under development by a number of pharmaceutical and biotechnology companies for several years, in various types of cancer. GDC – 0084 is distinguished from most molecules in the class by its ability to cross the blood – brain barrier, potentially making it suitable for cancers of the central nervous system. Genentech has completed a phase I study of GDC – 0084 in patients with r ecurrent GBM, and data was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL in June 2016 2 . The study recruited 47 patients at five centres in the United States and Spain, including UCLA, Dana – Farber Cancer Institute, and Massachusetts General Hospital. In addition, GDC – 0084 has an open Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA), and the transaction includes a quantity of pre – manufactured drug substance that is expected to be sufficient to support a proposed phase II clinical trial. Novogen CEO, Dr James Garner, commented, "We are excited that Genentech has entrusted us to take forward this promising investigational medicine in one of the most challenging areas of cancer treatment. This is a transformative step for Novogen, and the a ddition of GDC – 0084 to our portfolio strengthens our position as an emerging oncology biotech company. Our pipeline is now diversified across three distinct technology platforms, and we anticipate it will provide a rich flow of value – driving milestones as the company progresses." He added, "The PI3K inhibitor class is well – validated and is of considerable interest to larger pharmaceutical companies. While a number of development candidates are in clinical trials across a range of cancer types, we believe GDC-0084 is well differentiated and represents an important opportunity to contribute to the treatment of patients with glioblastoma." Under the terms of the agreement, Novogen will pay Genentech an upfront payment of US$ 5 million and performance – related co nsideration linked to regulatory and commercial outcomes. In addition, Genentech will receive royalty payments in – line with industry benchmarks. Genentech will immediately initiate transfer of the IND for GDC – 0084 to Novogen, as well as key manufacturing and analytical processes. Novogen anticipates being able to provide an update to the market in the design, project cost, and timelines of the proposed phase II study early in the new year

On October 31, 2016 Merck KGaA, Darmstadt, Germany, and Pfizer Inc. (NYSE: PFE (link is external)) reported that the European Medicines Agency (EMA) has validated for review Merck KGaA, Darmstadt, Germany’s Marketing Authorization Application (MAA) for avelumab, for the proposed indication of metastatic Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, which impacts approximately 2,500 Europeans a year (Press release, Pfizer, OCT 31, 2016, View Source [SID1234516116]).[1],[2] Validation of the MAA confirms that submission is complete and begins the EMA’s centralized review process.* If approved, avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, could be the first approved treatment indicated for metastatic MCC in the EU. Patients with metastatic MCC face a very poor prognosis, with less than 20 percent surviving beyond five years.[3]

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"While early-stage Merkel cell carcinoma can be generally managed with surgery, there are significant unmet needs in metastatic disease, where treatment options are severely limited," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "We are pleased that the EMA is initiating its review of avelumab, as this means we are one step closer to bringing a much-needed new treatment option to European patients."

"This is the first of what we hope will be many regulatory milestones for avelumab," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We are committed to evaluating avelumab in a number of hard-to-treat cancers, and we believe it may have potential to be an important treatment option for patients with metastatic Merkel cell carcinoma."

The avelumab metastatic MCC MAA submission is supported by data from JAVELIN Merkel 200, a multicenter, single-arm, open-label, Phase II study of 88 patients with metastatic MCC whose disease had progressed after at least one chemotherapy treatment.[1] The JAVELIN Merkel 200 study represents the largest data set of any anti-PD-L1/PD-1 antibody reported in this patient population. These data were recently published in the Lancet Oncology.[1]

Avelumab received an Orphan Drug Designation (ODD) from the European Commission for MCC. To qualify for an ODD in the EU, a medicine must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; the prevalence of the condition in the EU must not be more than 5 in 10,000, or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development; and it must be for a disease where no satisfactory treatment is currently available.[4]

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and over 2,900 patients evaluated across more than 15 different tumor types. In addition to metastatic MCC, these cancers include breast, gastric/gastro-esophageal junction, head and neck, Hodgkin’s lymphoma, melanoma, mesothelioma, non-small cell lung, ovarian, renal cell carcinoma and urothelial (primarily bladder).

*Avelumab is not approved for any indication in any market. This marks the first acceptance of an EU market authorization application to review the safety and efficacy results for the investigational product avelumab.

On October 31, 2016 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported that the U.S. Food and Drug Administration (FDA) has accepted for review the Abbreviated New Drug Application (ANDA) for generic doxorubicin hydrochloride (HCI) liposome injection submitted by its partner Actavis LLC (an indirect, wholly owned subsidiary of Teva Pharmaceuticals USA, Inc.) (Press release, Merrimack, OCT 31, 2016, View Source [SID1234516115]). This is the first product developed by Merrimack under a partnership agreement with Actavis LLC pursuant to which Merrimack is responsible for the development and commercial supply of bulk drug product and Actavis LLC is responsible for fill/finish activities, regulatory approvals and commercialization in the United States.

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Doxorubicin HCl liposome injection is marketed as DOXIL in the United States by Janssen Products LP, a Johnson & Johnson company. The approved indications for the product are ovarian cancer, AIDS-related Kaposi’s sarcoma and multiple myeloma. DOXIL generated approximately $600 million annually in global revenue prior to Johnson & Johnson’s 2011 manufacturing disruption, which resulted in the placement of DOXIL on the FDA’s drug shortage list. While DOXIL was on the drug shortage list, the FDA approved a generic version of doxorubicin HCl liposome injection marketed by Sun Pharma Global FZE, and both products now share the U.S. market. If approved, Merrimack is eligible to receive a royalty rate in the mid-twenties of net profits on sales of doxorubicin HCl liposome injection under the agreement with Actavis.

"We are pleased to have achieved this important milestone with our partner, Actavis," said Gary Crocker, Chairman of Merrimack’s Board of Directors and interim President and CEO. "This collaboration leverages Merrimack’s proven expertise in the development of liposomal products and provides the opportunity to maximize the use of our state-of-the-art commercial liposomal manufacturing facility. It also could allow us, if the product is approved, to generate an additional revenue stream to not only offset costs but meaningfully improve earnings. We look forward to the FDA’s review of Actavis’s ANDA filing and providing further support as Actavis navigates the regulatory approval process."

Merrimack is a leader in the development and manufacturing of nanoliposomal products. In addition to the generic doxorubicin HCl liposome injection for which the ANDA was just accepted, Merrimack has developed or is developing several novel therapeutic candidates. Merrimack’s first commercial product, ONIVYDE (irinotecan liposome injection), is a novel liposomal formulation of irinotecan that was approved by the FDA in the United States in October 2015.