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H3 Biomedicine to Present New Data on H3B-6527, an FGFR4 Inhibitor, at the 2017 International Liver Cancer Association Annual Meeting

On September 15, 2017 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of precision medicines for oncology and a member of Eisai’s global Oncology Business Group, reported that company scientists will present data from pre-clinical studies involving one of its oncology drug candidates, H3B-6527 (Press release, H3 Biomedicine, SEP 15, 2017, View Source [SID1234520544]). This data was accepted as an oral presentation at the 2017 International Liver Cancer Association (ILCA) annual meeting taking place September 15-17, 2017 in Seoul, Republic of Korea.

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H3 Biomedicine’s oral presentation is scheduled at 3:30 p.m. on Friday September 15, in Grand Ballroom 1 & 2, Lobby Level. The presentation will overview H3B-6527, an orally bioavailable, highly selective and potent inhibitor of fibroblast growth factor receptor 4 (FGFR4), which is currently in an ongoing Phase I clinical study in advanced hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). The presentation will be given by H3 scientist and lead author, Anand Selvaraj, Ph.D.

"The data being presented at ILCA highlight the excellent progress H3’s scientists have made within this program and demonstrate that FGF19 expression is a predictive biomarker for response to H3B-6527 therapy in non-clinical studies," said Markus Warmuth, M.D., President and CEO of H3 Biomedicine. "These results highlight the potential for FGFR4 inhibition with H3B-6527, and we are excited to continue with our research to determine if it may provide clinical benefit to patients who have been diagnosed with HCC and IHCC."

The study revealed that biochemical and cellular selectivity assays showed that H3B-6527 is >250 fold selective towards FGFR4 compared to other FGFR isoforms. Addition of H3B-6527 to FGF19 amplified HCC cell lines led to dose dependent inhibition of FGF19/FGFR4 signaling and concomitant reduction in cell viability. In a panel of 40 HCC cell lines, H3B-6527 selectively reduced the viability of cells that harbor FGF19 amplification and showed no effect in FGF19 non-amplified HCC cell line models. Oral dosing of H3B-6527 to mice led to dose-dependent pharmacodynamic modulation of FGFR4 signaling and tumor regression in FGF19 altered HCC cell line derived xenograft models. H3B-6527 demonstrated inhibition of tumor growth in an orthotopic liver xenograft model of FGF19 altered HCC grown in nude mice. Importantly, the inhibition of tumor growth occurred at doses that were well tolerated in mice and no evidence of FGFR1-3 related toxicities were observed at efficacious doses.

"We are extremely pleased with the results of this work and the progress the program has made, to date," said Pete Smith, Ph.D., Chief Scientific Officer, H3 Biomedicine. "H3B-6527 demonstrated tumor regressions in multiple patient-derived xenograft models with high FGF19 expression and has shown excellent combination potential with standard-of-care and experimental agents. The data described in the presentation support the ongoing clinical development of H3B-6527 and highlight our aim to select patients most likely to respond to H3B-6527 treatment."

About H3B-6527

H3B-6527 is a selective, orally bioavailable, and potent inhibitor of fibroblast growth factor receptor 4 (FGFR4) that is being investigated for the treatment of advanced hepatocellular carcinoma (HCC). Aberrant signaling through the FGF19-FGFR4 axis has been shown to drive tumor development and dependency in pre-clinical models of HCC. H3B-6527 has shown sustained tumor regressions in several preclinical models of HCC where FGF19-FGFR4 signaling is aberrantly activated. The safety and preliminary efficacy of H3B-6527 will be explored in patients that are selected using a companion diagnostic that identifies HCC with activated FGF19-FGFR4 pathway activity. H3B-6527 is currently in Phase 1 clinical trials. For more information on the clinical trial, please click here.

TESARO Receives Positive CHMP Opinion for ZEJULA®

On September 15, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the Company’s marketing authorization application (MAA) for ZEJULA (niraparib) as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete response (CR) or partial response (PR) to platinum-based chemotherapy (Press release, TESARO, SEP 15, 2017, View Source [SID1234520538]). This opinion will now be referred to the European Commission (EC), which grants marketing authorization for medicines in the European Union. Pending the decision by the EC, ZEJULA would be the first oral, once-daily poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor approved in Europe for use in patients regardless of BRCA mutation or biomarker status.

ZEJULA was approved by the Food and Drug Administration (FDA) on March 27, 2017 and is marketed by TESARO in the United States, where it is the most frequently prescribed PARP inhibitor.

"ZEJULA was studied with the highest level of clinical rigor, and the Phase 3 NOVA trial generated unsurpassed efficacy results in patients with recurrent ovarian cancer, including women without germline BRCA mutations who have the most challenging prognosis and few treatment options," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Today’s positive CHMP opinion brings us one step closer to providing this important new medicine to a broad population of patients with recurrent ovarian cancer in Europe."

The ZEJULA marketing authorization application is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased progression free survival (PFS) in patients with and without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (HR 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

The most common grade 3/4 adverse reactions to ZEJULA in the NOVA trial included thrombocytopenia (34%), anemia (25%), neutropenia (20%), and hypertension (9%). Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low; approximately 1% after month two. The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3.3%, 1.9% and 1.4% of patients, respectively.

"This is an important milestone for TESARO, marking our second positive CHMP opinion for our portfolio in 2017. We are rapidly globalizing the Company’s mission of providing transformative oncology therapies to those who need them most," said Orlando Oliveira, Senior Vice President and General Manager of TESARO International. "Upon final approval by the EC, we intend to launch ZEJULA across multiple countries in Europe where we already have an established, direct presence, beginning in the fourth quarter."

About Ovarian Cancer in Europe
Europe has one of the highest incidences of ovarian cancer in the world with approximately 45,000 women diagnosed there every year1,[2]. Ovarian cancer affects approximately 1.3 in 10,000 people in the European Union, where it is the sixth-most common cancer among women and the fifth-most frequent cause of cancer death among women3,[4]. Despite high initial response rates to platinum-based chemotherapy, approximately 85% of women with advanced ovarian cancer will experience a recurrence of the disease after first-line treatment. The efficacy of chemotherapy also diminishes over time.

TECENTRIQ GO29695 (NCT02431208) and BO29562 (NCT02631577) partial clinical hold reactive statement

On September 15, 2017 Roche reported that based on emerging safety data from clinical trials evaluating pembrolizumab in combination with either lenalidomide or pomalidomide in multiple myeloma, the FDA has requested that a Phase Ib and a Phase Ib/II TECENTRIQ study be placed on partial clinical hold (Press release, Hoffmann-La Roche, SEP 15, 2017, View Source [SID1234520536]). At Roche/Genentech we remain committed to patient safety and will continue to work closely with the FDA. It is our understanding that the FDA is evaluating all ongoing blood cancer trials investigating an anti-PD1/PDL1 medicine in combination with an immunomodulatory medicine to determine if it is a class-wide (anti-PD1/PDL1) concern in multiple myeloma/blood cancers or a specific concern with certain combinations with immunomodulatory medicines.

The two studies include cohorts evaluating TECENTRIQ in combination with an immunomodulatory medicine (IMiDs) in relapsed/refractory multiple myeloma and relapsed/refractory follicular lymphoma. While the partial clinical hold is in place, patients who are currently enrolled in these trials and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled. Although the trials are early and ongoing, we have not seen evidence of similar findings of increased death or serious events with the use of TECENTRIQ in combination with immunomodulatory medicines.

Bristol-Myers Squibb and Halozyme Enter Global Collaboration and License Agreement for ENHANZE Technology

On September 14, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Halozyme Therapeutics, Inc. (NASDAQ:HALO) reported a global collaboration and license agreement to develop subcutaneously administered Bristol-Myers Squibb immuno-oncology medicines using Halozyme’s ENHANZE drug-delivery technology (Press release, Bristol-Myers Squibb, SEP 14, 2017, View Source [SID1234530558]).

"We are excited to partner with Halozyme to pursue potential new approaches to how our medicines are delivered to patients," said Murdo Gordon, chief commercial officer, Bristol-Myers Squibb. "Through our work with Halozyme, we hope to improve the patient treatment experience by developing flexible and convenient treatment delivery options."

The Halozyme ENHANZE technology is based on a proprietary recombinant human hyaluronidase enzyme (rHuPH20) that temporarily degrades hyaluronan — a glycosaminoglycan or chain of natural sugars in the body — to aid in the dispersion and absorption of other injected therapeutic drugs. This technology may allow for more rapid delivery of large volume injectable medications, such as medications that are currently delivered intravenously, through subcutaneous delivery.

"Bristol-Myers Squibb has one of the industry’s most advanced and extensive immuno-oncology portfolios with a clear commitment to patient-centered innovation," said Dr. Helen Torley, president and chief executive officer of Halozyme. "Through this collaboration we are excited to explore the potential for ENHANZE to expand the number of cancer patients who may receive their therapies as a rapidly administered subcutaneous injection."

Under the terms of the agreement, Halozyme will receive an initial $105 million for access to the ENHANZE technology. Bristol-Myers Squibb has designated multiple immuno-oncology targets including programmed death 1 (PD-1) and has an option to select additional targets within five years from the effective date. The collaboration may extend to a maximum of 11 targets. Halozyme has the potential to earn milestone payments of up to $160 million for each of the nominated collaboration targets and additional milestone payments for combination products, subject to achievement of specified development, regulatory and sales-based milestones. In addition, Bristol-Myers Squibb will pay Halozyme royalties on sales of products using the ENHANZE technology developed under the collaboration.

The agreement is subject to customary anti-trust clearance by the U.S. Justice Department and Federal Trade Commission pursuant to the Hart-Scott-Rodino Act.

For Bristol-Myers Squibb, the transaction is expected to be dilutive to Non-GAAP earnings per share (EPS) in 2017 and 2018 by approximately $0.01, and by approximately $0.05 in 2019.

About ENHANZE Technology

Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

10-Q – Quarterly report [Sections 13 or 15(d)]

Oncbiomune has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, OncBioMune Pharmaceuticals, 2017, SEP 14, 2017, View Source [SID1234522112]).