On July 23, 2018 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage company developing novel epigenetic therapies, reported the appointment of Dr. Shefali Agarwal as chief medical officer, effective July 23, 2018 (Press release, Epizyme, JUL 23, 2018, View Source [SID1234527842]). In this role, Dr. Agarwal will oversee all of the company’s activities related to the global strategic development of tazemetostat, a potent, selective, orally available EZH2 inhibitor, as well as additional pipeline candidates. A trained physician with expertise in medical oncology, Dr. Agarwal brings nearly two decades of clinical research and regulatory experience to Epizyme.

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"Dr. Agarwal’s distinguished career in both academia and the biotech industry make her an ideal candidate to lead our clinical organization and oversee the development of innovative therapies to potentially treat a range of solid tumor and hematological malignancies for which significant needs exist," said Robert Bazemore, president and chief executive officer of Epizyme. "Her proven leadership and understanding of the patient community, as well as the healthcare providers who care for them, will be instrumental as we continue to advance our lead product candidate, tazemetostat."

"I look forward to joining this dynamic management team, and leading the next phase of clinical development for tazemetostat, as well as for EZM8266, our novel agent that targets G9a for the treatment of sickle cell disease, as we prepare it to enter the clinic," said Dr. Agarwal. "I believe that Epizyme’s scientific vision and innovative approach will drive the continued success of the company, as we work together to deliver promising new options for underserved patients."

Over the span of her career, Dr. Agarwal has held leadership positions across medical research, clinical development, clinical operations, and medical affairs. She has led clinical and regulatory engagements for small molecules, biologics, liposomal and cell therapy products across the full spectrum of drug development, from pre-IND work to filing. Dr. Agarwal most recently served as chief medical officer at SQZ Biotech, where she built and led the clinical development organization, which included clinical research operations and the regulatory function. She brings significant oncology experience to Epizyme, having held leadership positions at Curis and Tesaro. At Curis, Dr. Agarwal oversaw the Phase 2 study for its dual HDAC/PI3K inhibitor in diffuse large B-cell lymphoma, and the Phase 1 study in solid tumors for its oral checkpoint inhibitor. At Tesaro, Dr. Agarwal led the NDA and EMA submissions for ZEJULA (niraparib) in ovarian cancer. She has also held positions of increasing responsibility at Covidien, AVEO Oncology and Pfizer.

In addition to receiving her MBBS medical degree from Karnataka University’s Mahadevappa Rampure Medical School in India, Dr. Agarwal earned a master’s of public health from Johns Hopkins University, where she led clinical research in the Department of Anesthesiology and Critical Care Medicine. She also holds a master’s of science in business from the University of Baltimore’s Merrick School of Business.

On July 23, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has successfully completed a study on the stability after "hand thawing" syringes of the Cell-in-a-Box encapsulated cells that will be used, in combination with low doses of the cancer prodrug ifosfamide, for the treatment of locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, JUL 23, 2018, View Source [SID1234528930]). The data obtained from this "hand thawing" study is required by the U.S. Food and Drug Administration (FDA).

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The filing of an Investigational New Drug Application (IND) requires that the clinical product, as well as the product’s use, should be well characterised. PharmaCyte’s Cell-in-a-Box is a cutting edge Advanced Therapy Medicinal Product (ATMP). Therefore, numerous studies are needed since such a product has never been tested before in the United States. The laboratory scale "thawing" study previously conducted (View Source) determined how long the once-frozen Cell-in-a-Box encapsulated cells are still fit for use after thawing, as would occur in a clinical setting before the Cell-in-a-Box capsules are implanted into a patient with LAPC. That study defined one of the important parameters for the upcoming planned clinical trial for LAPC.

At individual study sites, the frozen cells in the Cell-in-a-Box capsules within syringes will be hand-thawed and then kept at room temperature until they are implanted into a patient with LAPC. The results of the "hand thawing" study announced today show that the viability of the cells remains essentially the same for at least 30 minutes at room temperature. This serves to define the time that the interventional radiologist has to implant the Cell-in-a-Box capsules after thawing to ensure cellular viability within the patient.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, explained the significance of the study saying, "This is yet another important study that PharmaCyte has completed to comply with the FDA’s requirements for our planned, upcoming clinical trial in LAPC. The Cell-in-a-Box encapsulated cells are in a frozen state before they are administered to the patient. This study was designed to determine how long after unfreezing the Cell-in-a-Box encapsulated cells can they be held at room temperature before being introduced into the patient without losing their effectiveness.

"This is important since the treatment depends on the viability of our genetically engineered live human cells in order to produce the cytochrome P450 enzyme for the activation of the chemotherapy prodrug ifosfamide. The study’s goal was to determine how long the cells remained viable at room temperature after thawing; thus, mimicking how long the clinicians and interventional radiologists will have to administer the capsules to the patient in the hospital. The newly completed studies show how long that Cell-in-a-Box encapsulated cells can be kept at room temperature for optimal activity."

On July 22, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its investigational BTK inhibitor zanubrutinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Waldenström macroglobulinemia (WM) (Press release, BeiGene, JUL 22, 2018, View Source;p=RssLanding&cat=news&id=2359338 [SID1234527801]). Based on BeiGene’s discussions with the FDA, internal review of available data from its global Phase 1 trial of zanubrutinib in patients with WM, and supported by the Fast Track Designation, BeiGene is preparing to submit in the first half of 2019 a New Drug Application (NDA) to pursue an accelerated approval of zanubrutinib for patients with WM based on results from the global Phase 1 study. A final determination to submit the NDA will be made subsequent to the pre-NDA meeting with FDA after obtaining mature data from the study this fall.

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"We believe zanubrutinib is a differentiated BTK inhibitor based on the depth and durability of responses observed in our ongoing global Phase 1 trial of zanubrutinib in WM patients. We look forward to working closely with the FDA in the continuing development of zanubrutinib for the treatment of this disease," commented John Oyler, co-founder, CEO and Chairman of BeiGene. "We are hopeful that zanubrutinib, if approved, may represent a valuable and important treatment option for patients with WM."

The FDA’s Fast Track program is intended to expedite or facilitate the process for reviewing new drugs that are intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and demonstrate the potential to address unmet medical needs for the condition. A drug candidate with a Fast Track Designation may be eligible for more frequent communications with the FDA, for Accelerated Approval and Priority Review (if relevant criteria are met), and rolling review of the NDA.

In addition to the global Phase 1 trial of zanubrutinib, which enrolled 76 WM patients to date, zanubrutinib is also being tested in a global Phase 3 clinical trial in patients with WM comparing zanubrutinib to ibrutinib, a currently approved BTK inhibitor. BeiGene announced today that this global Phase 3 study has completed patient enrollment. In addition, zanubrutinib is being tested in a global Phase 3 clinical trial as a first-line treatment for patients with chronic lymphocytic leukemia (CLL) and a Phase 2 clinical trial in patients with relapsed or refractory follicular lymphoma in combination with GAZYVA (obinutuzumab). In China, BeiGene has completed enrollment in three pivotal Phase 2 clinical trials of zanubrutinib in patients with mantle cell lymphoma (MCL), CLL and WM, and expects to file an NDA in China for MCL this year. BeiGene is also planning a Phase 3 trial for a head-to-head comparison of zanubrutinib versus ibrutinib in patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL). As of May 7, 2018, more than 1,200 patients have been enrolled in the zanubrutinib development program.

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various B cell malignancies.

On July 22, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary topline results from the independent review of response data from the pivotal Phase 2 trial of tislelizumab, an investigational anti-PD-1 antibody, in Chinese patients with relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL) (Press release, BeiGene, JUL 22, 2018, View Source;p=RssLanding&cat=news&id=2359339 [SID1234527802]).

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"We are excited to announce the preliminary topline results from our first pivotal trial for tislelizumab. Despite short follow-up, we believe there was a demonstration of robust activity, with high overall and complete response rates in addition to a safety profile that is consistent with other PD-1 inhibitors. We believe these strong results will support our first regulatory filing in China for tislelizumab, which is planned for later this year," commented Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene.

The single-arm pivotal trial enrolled 70 patients with cHL who either failed autologous stem cell transplantation (ASCT) or who were ineligible for ASCT. The primary endpoint was overall response rate (ORR) as defined by the Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, time to response, safety, and tolerability. As of the data cutoff, the median follow-up time was approximately 6.0 months. A review of responses by an independent review committee, provided in June 2018, demonstrated:

The ORR was 73 percent, including 50 percent CR, and the median DOR had not been reached.

Frequency and severity of adverse events were generally consistent with the previously reported Phase 1 safety and tolerability data for tislelizumab, or, in the case of certain immune-related events such as hypothyroidism and fever, consistent with previous reports of other PD-1 antibodies for the treatment of cHL.
These cHL data, along with additional follow-up data from the clinical trial, are expected to be included in BeiGene’s Biologics License Application (BLA) planned to be filed with the China Drug Administration (CDA) later this year. Full results of the trial are expected to be presented at an upcoming medical conference.

Tislelizumab is also being studied in global Phase 3 trials in a number of malignancies, including non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma; as well as two global Phase 2 trials in patients with previously treated hepatocellular carcinoma or with R/R mature T-and NK-cell lymphomas, and an additional pivotal Phase 2 trial in China in urothelial cancer.

About Classical Hodgkin’s Lymphoma
Classical Hodgkin’s lymphoma is one of the two major types of lymphoma that begin in the lymph nodes and tissues of the lymphatic system. All other lymphomas are classified as non-Hodgkin’s lymphomas. Hodgkin’s lymphoma is characterized by the presence of very large cells called Reed-Sternberg cells, although other abnormal cell types may be present. According to the Lymphoma Research Foundation, Hodgkin’s lymphoma is less common than non-Hodgkin’s lymphoma. There were approximately 2,100 diagnosed cases of Hodgkin’s lymphoma in China in 2012.1 Although the cancer can occur in both children and adults, it is most commonly diagnosed in young adults between the ages of 15 and 35 and in older adults over age 50.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On July 20, 2018 PureTech Health plc (LSE: PRTC) ("PureTech Health"), a clinical-stage biopharmaceutical company developing novel medicines focused on the Brain-Immune-Gut (BIG) Axis, reported that it has entered into a multiyear collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., to advance PureTech’s milk-derived exosome platform technology for the oral administration of Roche’s antisense oligonucleotide platform (Press release, PureTech Health, JUL 20, 2018, View Source [SID1234536199]). Under the terms of the agreement, PureTech Health will receive up to $36 million, including upfront payments, research support, and early preclinical milestones. PureTech Health will be eligible to potentially receive development milestone payments of over $1 billion and additional sales milestones and royalties for an undisclosed number of products.

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PureTech’s milk exosome-based technology is uniquely designed to facilitate the oral administration of complex payloads such as nucleic acids, peptides, and small molecules. These exosomes are believed to traffic via lymphatic circulation and could potentially enable the targeting of immune cells in novel ways.

Daphne Zohar, Co-founder and Chief Executive Officer of PureTech Health, said: "We are excited to accelerate the development of this promising technology from our internal lymphatic and immune cell trafficking programmes. The expertise and resources that Roche is bringing to the collaboration will help us to potentially address one of the biggest challenges in oligonucleotide-based therapeutic development: oral administration of nucleic acids."

PureTech Health has been advancing internal research and development projects that focus on the Brain-Immune-Gut (BIG) Axis, with an emphasis on lymphatics and immune cell trafficking to modulate immunity in a tissue-specific manner. These internal pipeline programmes are being consolidated into a separate division of PureTech Health called Ariya. PureTech’s Internal division, which includes the milk-derived exosome technology, has generated compelling pre-clinical data and secured key intellectual property for its lymphatic and immune cell trafficking programmes.

About PureTech’s Milk Exosomes Technology

Milk exosomes represent a significant opportunity to potentially resolve the long-standing challenge of oral bioavailability of macromolecules and complex small molecules. Exosomes, which contain mixtures of lipids, proteins and nucleic acids, play a critical physiologic role in intercellular communication and the transport of macromolecules between cells and tissues. Mammalian-derived exosomes have attractive potential as vehicles for the administration of a variety of drug payloads, especially nucleic acids, since their natural composition will likely provide superior tolerability over the variety of synthetic polymers currently in use. Most sources of mammalian exosomes are not suitable or viable as vehicles for oral administration of drugs due to their lack of stability under the harsh physiologic conditions associated with transit through the stomach and small intestine; however, the milk-derived exosomes that form the basis for PureTech’s internally-developed technology have evolved naturally and specifically to accomplish the task of oral transport of complex biological molecules. The technology is based on research conducted by PureTech Health and its academic collaborators, including Ramesh Gupta, PhD, Agnes Brown Duggan Chair in Oncological Research at the James Graham Brown Cancer Center, and Professor in the Department of Pharmacology and Toxicology at University of Louisville, and exclusively licensed to PureTech Health.