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TTY Biopharm’s Anticancer Agent S-1 Received Reimbursement for Adjuvant Treatment of Locally-advanced Gastric Cancer

On December 13, 2016 TTY Biopharm’s (4105:TW) reported that anticancer agent S-1 Capsule received a Taiwan National Health Insurance (NHI) reimbursement for adjuvant chemotherapy of locally-advanced gastric cancer [stage II (excluding T1), IIIA or IIIB in TNM system], after the review from Pharmaceutical Benefit and Reimbursement Scheme Joint committee (PBRS) (Press release, TTY Biopharm, DEC 13, 2016, View Source [SID1234527287]). The validated date was December 1st, 2016. This was the second reimbursement indication after S-1 Capsule had received its first reimbursement for locally advanced un-resectable or metastatic pancreatic cancer patient since June, 2014. S-1 Capsule had been developed by Taiho Pharmaceutical Co., Ltd. of Japan and TTY Biopharm received an exclusive right to develop and market in Taiwan.

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According to Ministry of Health and Welfare’s database, around 3,600 to 3,800 new patients were diagnosed with gastric cancer annually. Gastric cancer was ranked the 7th in cancer incidence and 5th in mortality. For the early stage gastric cancer, the primary treatment was surgery; however, about 40% of patients who were diagnosed with stage II and III gastric cancer after surgery would still relapse and nearly 90% of the relapsed cases happened within 3 years. Unfortunately, for those relapsed patients, the median survival rate was less than 10%. The clinical practice recommended chemotherapy to be an adjuvant therapy. S-1 Capsule, after publication of a large-scale randomized Phase III clinical trial, was approved to be the first agent to decrease the risk of death by 33.1% and risk of relapse by 34.7% for stage II (excluding T1)-III gastric cancer patients. It was also the only oral chemotherapy agent with TFDA and NHI reimbursement label in Stage II-IIIB gastric cancer. Clinical results were first published on the New England Journal of Medicine and the final result was published on Journal of Clinical Oncology.

TTY Biopharm indicated: "Although the number of patients with gastric cancer has slowed down, the overall survival rate is lower than other Asian countries, Japan and South Korea for example. We keep not only reminding citizens to receive regular upper gastrointestinal examinations, but also educating public the benefits of adjuvant chemotherapy for lowering the risk of relapse and increasing chances of being cured." S-1 Capsule is expected to allow patients to maintain original lives. With reimbursement for gastric cancer patients, about 1,200 patients would be benefitted.

Actinium Pharmaceuticals Announces Submission of EU Orphan Designation Application for Actimab-A

On December 13, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that the Company has submitted an application with the European Medicines Agency (EMA) seeking Orphan Designation for Actimab-A for patients newly diagnosed with acute myeloid leukemia (AML) age 60 and above who are ineligible for currently used induction therapies (Press release, Actinium Pharmaceuticals, DEC 13, 2016, View Source [SID1234517061]). Actimab-A is currently in a 53-patient, multicenter open label Phase 2 trial where it is being studied as a monotherapy in these patients who have low peripheral blast (PB) burden. In a previously completed Phase 1 trial, Actimab-A showed a 50% composite response rate at the dose level of 2.0 μCi/kg/fraction, which is the dose level being studied in the current Phase 2 trial, in patients with low PB burden.

"Orphan designation brings significant benefits to the drug development process," said Sandesh Seth, Executive Chairman of Actinium Pharmaceuticals. "We are excited to have submitted this application with the EMA and we are optimistic that Actimab-A will soon have orphan designation in the EU just as it does in the U.S. If this were to occur, both of our clinical product candidates, Iomab-B and Actimab-A, would have orphan designation in the U.S. and EU, which are the largest addressable markets for our product candidates."

About EU Orphan Designation

The EMA, through its Committee for Orphan Medicinal Products (COMP), examines applications for orphan designation. To qualify for orphan designation, the prevalence of the condition must be less than 5 in 10,000, it must be life threatening or chronically debilitating and there must be no satisfactory method of treating the condition. Sponsors who obtain orphan designation receive numerous incentives including protocol assistance, a reduction or waving of fees and 10 years of market exclusivity should the therapy be approved. The process of filing and receiving the orphan medicines designation can take between eight to fourteen months in most cases. To learn more please visit EMA’s COMP website View Source

About Actimab-A

Actimab-A, Actinium’s most advanced alpha particle immunotherapy (APIT) product candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer calls. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML age 60 and above.

CytomX Announces Selection by Bristol-Myers Squibb of First Clinical Candidate Probody From Collaboration

On December 13, 2016 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported that Bristol-Myers Squibb Company has selected a clinical candidate for its CTLA-4 Probody program under the strategic oncology collaboration established in May 2014 (Press release, CytomX Therapeutics, DEC 13, 2016, View Source [SID1234517059]). Achieving this milestone results in a $2 million payment to CytomX.

"Selecting a candidate for the CTLA-4 Probody program is a pivotal development in our partnership with CytomX Therapeutics and builds on our I.O. leadership," said Carl Decicco, Ph. D., Head of Discovery at Bristol-Myers Squibb. "We are studying the CTLA-4 Probody for its potential to deliver a next-generation anti-CTLA-4 therapy as we continue to explore transformational immuno-oncology medicines."

CTLA-4, a clinically validated inhibitory immune checkpoint protein, is the most advanced target from the companies’ collaboration, which now also includes three additional, unnamed targets in discovery.

"Advancing our CTLA-4 Probody program to clinical candidate stage with Bristol-Myers Squibb underscores the potential of the Probody platform to transform the field of immuno-oncology by delivering safer, more effective therapies," said Sean McCarthy, D.Phil., President and Chief Executive Officer of CytomX. "This partnership milestone, taken together with CytomX’s recently filed Investigational New Drug application for CX-072, a wholly owned PD-L1-directed Probody therapeutic, highlights the potential of our innovative platform to deliver a new generation of anti-cancer treatments."

About the Collaboration Agreement
Under the terms of the May 2014 agreement, CytomX granted Bristol-Myers Squibb exclusive worldwide rights to discover, develop and commercialize Probody therapeutics for up to four oncology targets. Bristol-Myers Squibb made an upfront payment of $50 million to CytomX in 2014, and is providing research funding over the course of the research term. Upon the selection of the third and fourth targets, Bristol-Myers Squibb paid CytomX selection payments. CytomX is also eligible to receive additional preclinical payments and up to $298 million in development, regulatory and sales milestone payments for each collaboration target, as well as tiered royalties rising from mid-single digit to low double digits on net sales of each product commercialized by Bristol-Myers Squibb.

Atreca Announces Lead Preclinical Projects in Cancer Immunotherapy and Additional Disease Indications

On December 12, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported positive preclinical findings generated using the Company’s Immune Repertoire Capture (IRC) technology, presented at the IBC Antibody Engineering & Therapeutics Conference being held in San Diego, California, December 11-15, 2016 (Press release, Atreca, DEC 12, 2016, View Source [SID1234522960]). In a presentation entitled "Analyzing B-cell Receptor Repertoires from Human Studies," Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research, provided a summary of key findings from the Company’s preclinical programs, including:

Atreca’s IRC technology has identified and generated antibodies from active human immune responses, including antibodies from cancer patients who have responded well to immunotherapy and other treatments, patients with autoimmune disease, vaccinated subjects, and patients with infections.
Atreca’s immuno-oncology program is advancing antibodies that selectively bind tumor tissue types beyond that of the original patient and display potent antitumor activity in vivo.
Dr. Emerling stated, "Atreca’s IRC platform has demonstrated in preclinical disease models the power of mining a patient’s own anti-tumor immunity. In one of our applications of IRC, we generate natively paired antibody heavy and light chain sequences from blood plasmablasts – activated B cells – that are critical to the body’s own immune response to cancer and pathogens. As our programs progress, we anticipate being able to advance these promising biologic agents for potential use in cancer immunotherapy, vaccines, and diverse additional therapeutic applications."

"Over the past year, Atreca has made substantial progress both in advancing our internal and partnered programs and attracting world-class experts to our leadership team and advisory group," said Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "We will continue to advance multiple programs through preclinical studies to the clinic, with a primary focus on cancer immunotherapy applications of our novel and proprietary IRC platform."

More information on the Antibody Engineering & Therapeutics Conference is available at: View Source

MacroGenics Licenses Synthon’s Technology to Develop an Anti-B7-H3 ADC

On December 12, 2016 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, and Synthon Biopharmaceuticals B.V., an international biopharmaceutical company with highly focused development activities for new molecular entities in the therapeutic areas of oncology and autoimmune diseases, reported they have entered a license and collaboration agreement for the development of MGC018, an antibody-drug conjugate (ADC) directed against solid tumors expressing B7-H3 (Press release, MacroGenics, DEC 12, 2016, View Source [SID1234517232]). This molecule is based on a MacroGenics proprietary B7-H3 antibody and Synthon’s proprietary duocarmycin-based, linker-drug technology.

Under the terms of the agreement, Synthon has licensed rights to its linker-drug technology to MacroGenics to enable future development and commercialization of MGC018. Synthon will also provide manufacturing support and supply ADC to MacroGenics and will be entitled to receive license fees, milestone payments and royalties based on successful development and commercialization of MGC018. Additional details of the transaction were not disclosed.

Based on favorable activity and safety profiles in the non-clinical setting, MacroGenics has selected MGC018 as its lead anti-B7-H3 ADC candidate. MacroGenics has recently initiated IND-enabling studies for this molecule.

"We are encouraged by the data generated with Synthon’s ADC platform and believe that MGC018 will nicely complement our broader portfolio of B7-H3-directed agents," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "The team at Synthon brings tremendous expertise in linker-drug chemistry and product development that complements our existing capabilities. We look forward to continuing to collaborate with them on this important molecule."

Jacques Lemmens, founder and CEO of Synthon added: "We are very pleased with this commercial licensing agreement with MacroGenics, which enables us to deploy our unique linker-drug technology against a therapeutic target that is complementary to those in our own pipeline. We believe that such collaborations are an important means to accelerate the availability of important therapeutic treatment options to patients who need them."

MacroGenics’ B7-H3 Franchise

MGC018 represents the third molecule in MacroGenics’ franchise of B7-H3-directed molecules. In addition to MGC018, MacroGenics is pursuing two other therapeutic product candidates utilizing different and complementary immune-based mechanisms of action. The leading program, enoblituzumab, is an Fc-optimized monoclonal antibody directed against B7-H3 and is currently in clinical testing as both monotherapy and in combination with either pembrolizumab or ipilimumab. The second program, MGD009, also in clinical testing, is a bispecific DART molecule designed to target tumors expressing B7-H3 by recruiting and expanding T cells at the tumor site. MacroGenics retains worldwide development and commercialization rights to all three of these programs.

Synthon’s Unique Technology Based on Duocarmycin Analogs

Antibody-drug conjugates are designed to combine the specificity of antibodies directed against tumor-associated targets with potent cytotoxicity. Upon internalization of the ADC, the antibody-bound cytotoxins are released intracellularly, leading to programmed tumor cell death.

While the cytotoxins used in the majority of advanced programs in the field prevent tubulin polymerization during cell division, Synthon’s differentiating linker-drug technology − which applies valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA) − is based on synthetic duocarmycin analogs, which bind to the minor groove of DNA and subsequently cause irreversible alkylation of DNA. This disrupts the nucleic acid architecture, which eventually leads to tumor cell death.

Duocarmycins are able to exert their mode of action at any phase in the cellular cycle, whereas tubulin binders will only attack tumor cells when they are in a mitotic phase. Growing evidence suggests that DNA damaging agents, such as duocarmycins, are more efficacious in tumor cell killing than tubulin binders, particularly in solid tumors.

Although based on natural products, Synthon’s proprietary ADC linker-drug technology uses fully synthetic duocarmycin analogs. The unique design of the selectively cleavable linker connecting the antibody to a duocarmycin prodrug leads to high stability in circulation, and induces efficient release of the cytotoxin in the tumor.