On November 15, 2018 Rakuten Aspyrian, a biotechnology company developing precision-targeted cancer therapies based on its proprietary Photoimmunotherapy platform, reported the appointment of Mickey Mikitani as chief executive officer (Press release, Rakuten Aspyrian, NOV 15, 2018, View Source [SID1234531388]). Mr. Mikitani, a global business leader, will also continue in his role of chairman. In conjunction, former CEO Miguel Garcia-Guzman, Ph.D. will transition to serve as Rakuten Aspyrian’s vice chairman and chief scientific officer to continue to build the company’s pipeline and drive innovation.

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Rakuten Aspyrian also announced the appointment of Takashi Toraishi, Ph.D. as chief operating officer. Dr. Toraishi will oversee clinical trials and commercialization of Rakuten Aspyrian’s products, as well as manage the growth of the organization.

"With our Photoimmunotherapy platform, Rakuten Aspyrian holds tremendous potential to offer alternative options for treating cancer," said Mr. Mikitani. "As CEO, I will harness this potential as we build a fully integrated biopharmaceutical company with research, development and world-wide commercialization capabilities. Our mission is to develop and commercialize a strong pipeline of treatment options based on Photoimmunotherapy to create a new platform for cancer treatments."

Mr. Mikitani joined the company as chairman in 2016 and has provided strategic direction and investment to support its corporate and clinical development. He is also the Chairman and CEO of Rakuten, Inc. [RKUNF], a leading Japanese global innovation company in e-commerce, communications and fintech, with the mission to contribute to society by creating value through innovation and entrepreneurship. Rakuten is also recognized as the Official Innovation and Entertainment Partner of one of the world’s most admired soccer clubs, FC Barcelona, as well as the jersey partner of NBA Champions, the Golden State Warriors.

Mr. Mikitani was awarded the Legion of Honour by the French government in recognition of contributions to the economy and culture of France. He also serves on the boards of the Tokyo Philharmonic Orchestra and Lyft, Inc. Mr. Mikitani received his B.A. of Commerce at Hitotsubashi University in Tokyo and his MBA at Harvard Business School. At Harvard, he was awarded the Alumni Achievement Award, one of the school’s highest honors.

Prior to his appointment as chief operating officer, Dr. Toraishi led operations as president of Rakuten Aspyrian Japan. Previously he was president of new service development company at Rakuten, Inc., where he spearheaded company-wide innovation initiatives and multiple joint ventures, shared economy and other companies. For nine years, Dr. Toraishi worked with McKinsey & Company, Tokyo, completing his tenure as partner and consultant to global medical device and equipment companies. He started his career as an assistant professor of engineering at the University of Tokyo and led the nuclear chemistry division of the Japan Atomic Energy Agency. Dr. Toraishi received his B.A. of Engineering and his Master of Engineering at the University of Tokyo, his Licentiate of Engineering, Nuclear Chemistry at the Royal Institute of Technology at Stockholm, as well as his Ph.D. in Nuclear Chemistry from the University of Tokyo.

On November 15, 2018 Myovant Sciences (NYSE: MYOV), a leading clinical-stage biopharmaceutical company focused on women’s health and endocrine diseases, reported its participation in the following upcoming investor conferences (Press release, Myovant Sciences, NOV 15, 2018, http://investors.myovant.com/news-releases/2018/11-15-2018-132944791 [SID1234531386]):

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Evercore ISI HealthConX Conference in Boston, MA. President and Chief Executive Officer, Lynn Seely, M.D., will participate in a fireside chat on Tuesday, November 27, 2018, at 9:30 a.m. ET.
Citi’s 2018 Global Healthcare Conference in New York, NY. Myovant will host meetings with investors on Wednesday, December 5 and Thursday, December 6, 2018.

A live webcast of the Evercore presentation will be accessible on the Events page under the Investors and Media section of the Myovant website at www.myovant.com. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay of the webcast will be available for 30 days following the conference.

On November 15, 2018 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, today reported preclinical data for its novel oral Chk1 inhibitor, SRA737, in a poster presented at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium held in Dublin, Ireland (Press release, Sierra Oncology, NOV 15, 2018, View Source [SID1234531379]).

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"Oncogene-driven high-grade serous ovarian cancers (HGSOC) with CCNE1 (gene encoding cyclin E) and MYCN pathway activation exhibit defective cell cycle checkpoint control and replicative stress. The DNA damage response effector kinase, Chk1, modulates the cellular response to replicative stress and has been shown to be upregulated in these subtypes of HGSOC," said Dr. Clare Scott, Professor at The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. "Our pre-clinical results show that the Chk1 inhibitor SRA737 has impressive efficacy in our most aggressive models of ovarian cancer."

As detailed in the poster, the efficacy of single agent SRA737 was explored in two cyclin E overexpressing HGSOC patient-derived xenografts (PDX), and also compared to olaparib, a PARP inhibitor recently approved for HGSOC. Both PDX models had pronounced amplification of CCNE1; one also harbored a MYCN amplification. Both PDX models were insensitive to standard platinum-based therapy and did not harbor BRCA1/2 or related gene mutations. Treatment with SRA737 resulted in significant and differentiated anti-cancer activity, including dose dependent tumor regression. As anticipated, the PARP inhibitor olaparib was inactive.

"Sierra’s ongoing SRA737-01 monotherapy and SRA737-02 low dose gemcitabine combination studies were recently prioritized for CCNE1-enriched HGSOC, a promising potential indication for Chk1 inhibition," stated Dr. Barbara Klencke, Chief Development Officer, Sierra Oncology. "We look forward to reporting clinical data from these studies in the first half of 2019."

The poster will be presented on Thursday, November 15th from 10:00 am – 5:30 pm (GMT).

Title: SRA737, a novel Chk1 inhibitor, shows efficacy in CCNE1-amplified and MYCN-overexpressing high-grade serous ovarian cancer patient-derived xenograft models

Authors: G.Y. Ho, H. Barker, C. Vanderberg, O. Kondrashova, E. Kyran, E. Lieschke, O. McNally, A. Hamilton, V. Heong, R. Hansen, S. Milutinovic, B. Strouse, M. Hedrick, C. Hassig, D. Bowtell, W. Matthew, C. Scott

About SRA737

SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). In cancer cells, intrinsic replication stress is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g., BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic replication stress and have utility as a monotherapy in a range of tumor indications. The combination of SRA737 with other modalities, such as other agents that target the DDR network and certain chemotherapeutics, may also provide synergistic anti-tumor activity via a variety of potential biological mechanisms. Importantly, the oral bioavailability of SRA737 may afford greater dosing flexibility for both monotherapy and combination therapy settings than is possible with intravenously administered agents.

SRA737 is currently being investigated in two Phase 1/2 clinical trials primarily focused on patients with ovarian cancer: SRA737-01, a monotherapy study, and SRA737-02, a drug combination study evaluating SRA737 potentiated by low dose gemcitabine. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor

On November 15, 2018 Constellation Pharmaceuticals, Inc., (Nasdaq: CNST) a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported that it will make a presentation on its EZH2 inhibition program in prostate cancer at an upcoming biomedical conference (Press release, Constellation Pharmaceuticals, NOV 15, 2018, View Source [SID1234531377]).

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Bill Bradley, Ph.D., Associate Director, Translational Sciences, at Constellation, will give a poster presentation at the EORTC / NCI / AACR (Free AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Dublin, Ireland, on November 16. The presentation is titled "EZH2 Inhibition as an Effective Treatment for Metastatic Castration-Resistant Prostate Cancer." The presentation discusses preclinical evidence showing the effectiveness of the EZH2 inhibitor CPI-1205 in treating metastatic castration-resistant prostate cancer (mCRPC) dependent on androgen receptor signaling (ARS). CPI-1205 was shown to combine synergistically with ARS inhibitors, such as enzalutamide or abiraterone acetate, to inhibit the growth of prostate cancer cell models and also was effective in overcoming mechanisms of resistance to ARS inhibitors. The poster also includes transcriptomic analysis, including single-cell RNA sequencing, highlighting the mechanisms by which CPI-1205 and its combination with ARS inhibitors restrict prostate cancer growth. The data shown in the poster supports the potential of EZH2 inhibition as a therapeutic approach for the mCRPC patient population and contributes to the rationale for Constellation’s ProSTAR trial of the EZH2 inhibitor CPI-1205 used in combination with ARS inhibitors.

About EZH2 Inhibition in Prostate Cancer

EZH2 is an enzyme that acts as an epigenetic writer and normally regulates gene expression by placing one or more methyl groups on a histone protein, leading to the suppression of gene expression programs. While this effect of EZH2 on gene expression is a normal part of cellular development, some cancers depend on an abnormal pattern of gene expression and re-direct EZH2 to genes that become abnormally repressed. Cancer cells with these abnormal gene expression programs may be more resistant to anti-cancer therapies.

There is a strong association between EZH2 expression and disease progression in metastatic castration-resistant prostate cancer (mCRPC), and a therapeutic approach that targets EZH2 may result in better outcomes than those achieved with approved therapeutic agents that treat mCRPC. In prostate cancer, the androgen receptor is a key regulator of gene expression and acts as the mediator of androgen signaling in prostate cells. The AR signaling pathway is the primary pathway used by prostate cancer cells to promote tumor growth. We believe that EZH2, by suppressing certain gene sets, enhances AR signaling, which can lead to increased tumor growth. In preclinical studies, we observed enhanced gene expression changes in prostate cancer cells treated with a combination of enzalutamide and CPI-1205 as compared to enzalutamide treatment alone. This corroborates our hypothesis that EZH2 functionally cooperates with androgen receptor signaling to promote prostate cancer growth.

We also believe that EZH2 is utilized by prostate cancer cells to establish resistance to ARS inhibitors. We have observed in preclinical studies that EZH2 inhibitors, such as CPI-1205, in combination with ARS inhibitors synergistically killed tumor cells and demonstrated activity in models that are resistant to ARS inhibitors.

About CPI-1205

CPI-1205 is a small molecule designed to promote anti-tumor activity by specifically inhibiting EZH2, an enzyme that suppresses target gene expression. In preclinical studies, we observed that CPI-1205 inhibited tumor growth as a single agent and synergistically enhanced the efficacy of cancer therapies, including ARS inhibitors in a prostate cancer model and immune checkpoint inhibitors in other solid tumor models. Based on these observations and the limited options for patients who progress on ARS inhibitors or immune checkpoint inhibitors, we have prioritized clinical development of CPI-1205 as a combination therapy with ARS inhibitors in prostate cancer and immune checkpoint inhibitors in solid tumors. We are currently conducting the ProSTAR trial. We previously completed a Phase 1 clinical trial of CPI-1205 as a monotherapy in patients with relapsed B-cell lymphoma in which CPI-1205 demonstrated clinical activity and was well tolerated.

About the ProSTAR Clinical Trial

ProSTAR is an open-label Phase 1b/2 clinical trial of CPI-1205 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide or abiraterone acetate, which are second-generation ARS inhibitors, in patients with mCRPC who previously progressed on treatment with either abiraterone acetate or enzalutamide. Patients who have previously progressed on treatment with abiraterone acetate are treated with a combination of enzalutamide and CPI-1205, and patients who previously progressed on treatment with enzalutamide are treated with a combination of abiraterone acetate and CPI-1205. In the Phase 1b portion of this trial, we aim to establish safety, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and a recommended Phase 2 dose of CPI-1205 with these agents. Based on results from the Phase 1b trial, we expect to select either abiraterone acetate or enzalutamide to be combined with the optimal dose regimen of CPI-1205 for the Phase 2 portion of the trial. In the Phase 2 trial, we will assess response rate as the primary endpoint, defined as the proportion of patients who have any of (i) a prostate-specific-antigen reduction of 50% or more from baseline, (ii) a decline of 30% or more in circulating-tumor-cell count from baseline or (iii) for patients with measurable soft tissue disease, an objective response, defined as a complete response or partial response per RECIST 1.1 criteria.

On November 15, 2018 Oragenics, Inc. (NYSE American:OGEN), a leader in the development of new antibiotics against infectious diseases and effective treatments for oral mucositis ("OM"), reported it has received clearance to enroll patients residing in Germany from the Paul Erlich Institute and patients residing in the United Kingdom from the Medicines and Healthcare products Regulatory Agency (MHRA), into its Phase 2 clinical trial of AG013, a live biotherapeutic product for the potential prevention and treatment of OM (Press release, Oragenics, NOV 15, 2018, View Source [SID1234531372]).

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"We are pleased with the receipt of regulatory Health Authority approvals in Germany and the United Kingdom. These approvals provide us with the opportunity to expand the number of clinical trial sites from which we can draw patients to participate in our clinical trial of AG013," stated Alan Joslyn, Ph.D., president and CEO of Oragenics, Inc. Dr. Joslyn continued "The approvals of Germany and the United Kingdom, further enhance our ability to complete the clinical study in 2019."

The ongoing Phase 2 trial is a double-blind, placebo-controlled, two-arm, multi-center trial, in which approximately 200 patients will be randomized in a 1:1 ratio to receive either AG013 or placebo. The purpose of the study (NCT03234465) is to evaluate the safety, tolerability and efficacy of topically administered AG013 compared to placebo for reducing the incidence and severity of OM in patients undergoing traditional chemoradiation for the treatment of head and neck cancer. Key measures include duration, time to development, and overall incidence of OM (using a World Health Organization scale) during the active treatment phase, which begins from the start of chemoradiation therapy and ends two weeks following its completion.

AG013, which has been granted Fast Track designation with the U.S. Food and Drug Administration and orphan drug status in Europe, is an Intrexon Actobiotics therapeutic candidate formulated to deliver the therapeutic molecule, human Trefoil Factor 1, to the mucosal tissues in the oral cavity in a convenient oral rinsing solution. Trefoil Factors are a class of peptides involved in the protection of gastrointestinal tissues against mucosal damage and play an important role in these tissues subsequent regeneration. The compound was designed by the company’s strategic partner, Intrexon Actobiotics NV, a wholly-owned subsidiary of Intrexon Corporation (NYSE: XON) whereby Oragenics, Inc. holds an exclusive world-wide license