On July 23, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) has initiated a Phase Ib/II proof-of-concept study of sulfatinib in pancreatic neuroendocrine tumors ("NET") patients and in biliary tract cancer ("BTC") patients in the U.S.. Sulfatinib is an oral small molecule angio-immuno kinase inhibitor that can simultaneously block tumor angiogenesis and immune evasion (Press release, Hutchison China MediTech, JUL 23, 2018, https://www.chi-med.com/sulfatinib-poc-pnet-btc-us/ [SID1234528657]). This study follows several trials that are underway in China, including two Phase III studies in pancreatic and non-pancreatic NET that commenced after positive results from a Phase II study, and a Phase II study in BTC patients. In addition, a Phase I dose escalation part of this study in the U.S. was recently completed.

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This proof-of-concept study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of sulfatinib as a monotherapy in (a) patients with advanced BTC that have progressed on standard first-line chemotherapy, and (b) in patients with advanced pancreatic NET. The primary and secondary endpoints include progression-free survival ("PFS") rate, objective response rate ("ORR"), disease control rate ("DCR"), duration of response ("DoR"), time to response, overall survival ("OS"), safety and tolerability. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT02549937.

About Sulfatinib
Sulfatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor ("VEGFR"), fibroblast growth factor receptor ("FGFR") and colony stimulating factor-1 receptor ("CSF-1R"), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Inhibition of the VEGFR signaling pathway can act to stop angiogenesis, the growth of the vasculature around the tumor, and thereby starve the tumor of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumor growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signaling pathway blocks the activation of tumor-associated macrophages, which are involved in suppressing immune responses against tumors. Its unique angio-immuno kinase profile supports sulfatinib as a potentially attractive candidate for exploration of possible combinations with checkpoint inhibitors against various cancers.

Sulfatinib is the first oncology candidate that we have taken through proof-of-concept in China and subsequently started clinical development in the U.S. We are currently conducting studies in six target patient populations on sulfatinib and retain all rights to sulfatinib worldwide.

About Sulfatinib Development in China
Sulfatinib is currently in development as a single agent for patients with NET, thyroid cancer and BTC in China.

Pancreatic NET: In March 2016, we initiated the SANET-p study, which is a randomized, double-blind, placebo-controlled, multi-center, Phase III pivotal registration trial to treat about 190 patients with low- or intermediate-grade, advanced pancreatic NET in China. The primary endpoint is PFS, with secondary endpoints including ORR, DCR, DoR, time to response, OS, safety and tolerability. Additional details of the SANET-p study may be found at clinicaltrials.gov, using identifier NCT02589821. We expect to complete enrollment in 2019 and present top-line results thereafter.

Extra-pancreatic NET: The SANET-ep study, which was initiated in December 2015, is similar to the SANET-p study and is targeted at treating about 270 patients with advanced extra-pancreatic NET in China. Additional details of the SANET-ep study may be found at clinicaltrials.gov, using identifier NCT02588170. We expect to complete enrollment in 2019 and present top-line results thereafter.

Thyroid cancer: In March 2016, we initiated Phase II in two target patient populations in China to evaluate the efficacy and safety of sulfatinib in patients with advanced medullary thyroid cancer and iodine-refractory differentiated thyroid cancer. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02614495.

BTC: In January 2017, we began a Phase II study in patients with BTC (also known as cholangiocarcinoma), a heterogeneous group of rare malignancies arising from the biliary tract epithelia. Gemzar is the currently approved first-line therapy for biliary tract cancer patients, with a total of approximately 18,000 new patients per year in the U.S. according to the National Cancer Institute, but median survival is less than 12 months for patients with unresectable or metastatic disease at diagnosis. As a result, we see a major unmet medical need for patients who have progressed when being treated with Gemzar, and sulfatinib may offer a new targeted treatment option in this tumor type. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02966821.

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 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 SELLAS Life Sciences Group Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the Company’s lead asset, galinpepimut-S (GPS), for the treatment of multiple myeloma (MM) (Press release, Sellas Life Sciences, JUL 20, 2018, View Source [SID1234527797]). GPS is licensed from Memorial Sloan Kettering Cancer Center and targets the Wilms Tumor 1 (WT1) protein, which is present in an array of tumor types.

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The Company reported final clinical and immunological data from a Phase 2 clinical trial for GPS in the treatment of high-risk multiple myeloma at the 44th Annual European Society for Blood and Marrow Transplantation (EBMT) Meeting on March 19, 2018.

The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions that have the potential to address unmet medical needs. A product candidate with Fast Track status is afforded greater access to the FDA for the purpose of expediting the product candidate’s development, review and potential approval. For a product candidate with Fast Track designation, the FDA may consider sections of its Biologics License Application (BLA) for review on a rolling basis before the complete application is submitted if relevant criteria are met.

"The designation of Fast Track for GPS represents important recognition by the FDA of the potential of this novel immunotherapeutic to address the significant unmet need in the treatment of patients with high-risk multiple myeloma in patients with poor-risk cytogenetics at diagnosis who still harbor minimal residual disease (MRD) after autologous stem cell transplant," said Angelos Stergiou, M.D., Sc.D. h.c., President and Chief Executive Officer of SELLAS. "We are fully committed to working closely with the FDA as we continue development of our potential first-in-class novel WT1-targeting cancer vaccine for select high-risk MM patients in the post-autotransplant maintenance setting after standard first-line treatment."

About the Phase 2 GPS multiple myeloma study

The open-label Phase 2 study consisted of 19 patients with multiple myeloma who had high-risk cytogenetics at initial diagnosis and remained at least minimal residual disease (MRD)-positive after a successful autologous stem cell transplant ("ASCT"). GPS was administered to patients in the study who achieved a stable disease or better status (per International Myeloma Working Group criteria) following ASCT. GPS was evaluated as consolidation therapy to potentially stimulate a highly-specific immune response against WT1 in order to prevent or delay myeloma progression. Median progression-free survival (PFS) of 23.6 months was reported in the high-risk disease setting, compared to historically inferior outcomes while on an immunomodulatory drug (IMID) or proteasome inhibitor post-ASCT maintenance. Median overall survival has not been reached to date. GPS stimulated time-dependent and robust CD4+ T cell or CD8+ T cell immune responses (IRs) specific for all four WT1 peptides within GPS, two of which are heteroclitic (mutated, by design). In addition, GPS stimulated similar IRs against the two counterpart native peptides. The IRs were confirmed in up to 91% of patients across HLA allele types, with multivalent IRs emerging in up to 64% of patients. Multifunctional cross-epitope T cell reactivity was observed in 75% of patients to antigenic epitopes against which hosts were not specifically immunized, in a pattern akin to epitope spreading. A link of clinical activity to antigen-specific immune responses was suggested.

About Galinpepimut-S (GPS):
GPS is a heteroclitic multivalent, multi-peptide cancer immunotherapeutic agent composed of four peptides, addressing over 20 epitopes, and derived from the WT1 protein, which has been ranked by the National Cancer Institute as a top priority among cancer antigens for immunotherapy. Importantly, because the WT1 antigen is overexpressed in many malignancies, and is not found in most normal tissues, GPS has the potential to be a broad immunotherapy, effective across a multitude of diverse cancer types and patient populations.