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Myovant Sciences Announces Completion of Enrollment in Phase 3 HERO Trial of Relugolix in Men with Advanced Prostate Cancer

On October 24, 2018 Myovant Sciences (NYSE: MYOV) reported it has completed patient enrollment in its pivotal Phase 3 clinical trial, HERO, which is evaluating the safety and efficacy of relugolix for the treatment of men with advanced prostate cancer (Press release, Myovant Sciences, OCT 24, 2018, http://investors.myovant.com/news-releases/2018/10-24-2018-133055538 [SID1234530139]). The HERO study is designed to support approval by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency.

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"Completion of enrollment in HERO is a critical milestone for our prostate cancer program," said Lynn Seely, M.D., President and CEO of Myovant. "We look forward to reporting top-line efficacy and safety data for HERO in the fourth quarter of 2019. Relugolix is the only oral gonadotropin-releasing hormone, or GnRH, receptor antagonist in development to lower testosterone and prostate-specific antigen, or PSA, in men with prostate cancer."

Pending positive Phase 3 results, Myovant expects to submit a New Drug Application for relugolix with the FDA in early 2020. If approved, relugolix has the potential to be the first oral GnRH receptor antagonist approved for the treatment of advanced prostate cancer. Relugolix is administered as one pill once-daily and has been shown to decrease testosterone and PSA levels within days in Phase 1 and 2 clinical studies.

About the HERO Study
This randomized, open-label, parallel-group, international Phase 3 clinical trial is evaluating the safety and efficacy of relugolix in men with androgen-sensitive advanced prostate cancer who require at least one year of continuous androgen deprivation therapy. Patients enrolled in the study were randomized 2:1 to receive a single loading dose of relugolix 360 mg followed by relugolix 120 mg once daily or to treatment with leuprolide acetate 3-month depot injection, respectively. The primary efficacy outcome of the study is the ability of relugolix to achieve and maintain serum testosterone suppression to castrate levels (≤50 ng/dL [1.7 nmol/L]) for 48 weeks. A total of 934 patients have been enrolled in the HERO study in North and South America, Europe and the Asia-Pacific region.

About Advanced Prostate Cancer
Prostate cancer is the second most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the United States. According to the National Cancer Institute, approximately 2.9 million men in the United States are currently living with prostate cancer, and approximately 165,000 men are estimated to be newly diagnosed in 2018. Treatment for advanced prostate cancer typically involves treatment with androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castration levels. GnRH agonists, such as leuprolide depot, or slow-release injections are the current standard of care for medical castration. However, GnRH agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial rise in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery if the drug is discontinued.

OncoSec Announces Publication of Data in Nature Gene Therapy Demonstrating the Ability of its Newly Optimized Intratumoral IL-12 Immunotherapy Platform to Increase Systemic Anti-tumor Responses in both Treated and Untreated Lesions

On October 24, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the publication of a study in the peer-reviewed journal, Nature Gene Therapy (an open access article; View Source), demonstrating that the newly optimized intratumoral IL-12 immunotherapy platform (electroporation-mediated intratumoral IL-12 gene therapy) induces immunological changes in both locally-treated and distant, untreated tumors (Press release, OncoSec Medical, OCT 24, 2018, View Source [SID1234530143]). The publication provides new mechanistic insights into this systemic anti-tumor immunity including the observation that IL-12 primed effector T cells diminished expression of PD-1, which is particularly relevant to Oncosec’s ongoing KEYNOTE-695 clinical study.

The paper, titled "Characterization of abscopal effects of intratumoral electroporation-mediated IL-12 gene therapy," by Mukhopadhyay et al., reported results from a pre-clinical study of OncoSec’s optimized plasmid IL-12 (TAVO) therapeutic platform on both locally-treated and distant, untreated lesions, with a particular emphasis on understanding "abscopal" effects in distant non-electroporated tumors. Results from the study indicated that intratumoral IL-12 treatment led to an induction of IL-12-regulated genes, other cytokines and chemokines pathways, as well as genes for enhanced antigen processing and presentation in the treated tumor. These localized IL-12-mediated effects then led to the generation of systemic anti-tumor immune responses, including a surge of CD8+ T cells in the spleen and in non-treated tumors and when coupled with PD-1 modulation, suggests an orchestrated "armoring" of these effector T cells against T-cell checkpoints when primed in the presence of IL-12 in situ.

"Data from previously completed clinical and pre-clinical studies of our TAVO platform in multiple cancer settings has clearly demonstrated that our intratumoral electroporation-mediated IL-12 gene therapy is safe and produces systemic anti-tumor effects from a local delivery of this potent cytokine," said Christopher G. Twitty, PhD, Chief Scientific Officer of OncoSec. "Based on these outcomes, OncoSec is advancing an optimized version of TAVO that is designed to increase transgene expression and efficacy. The study published in Gene Therapy indicates that tumors treated directly with the optimized TAVO therapy rapidly engage IL-12/IFN-g regulated pathways, altering the tumor microenvironment’s immunogenicity and effectively creating an in situ vaccine that ultimately drives an increase of tumor infiltrating lymphocytes and immune-specific gene expression in both treated and distant untreated tumors, indicative of a de novo immune response. These results confirm that OncoSec’s TAVO platform may represent a mechanism by which local intratumoral IL-12 gene therapy can deliver a safe and effective abscopal response."

Orion and Bayer have completed the phase III trial of darolutamide in patients with non-metastatic castration-resistant prostate cancer – The primary endpoint was met

On October 24, 2018 Orion and Bayer reported that they have completed the phase III clinical trial (ARAMIS) of darolutamide, the novel oral androgen receptor antagonist for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Orion Pharma, OCT 24, 2018, View Source;the-primary-endpoint-was-met/ [SID1234530144]). The primary endpoint of the trial was met: Darolutamide significantly extended metastasis-free survival compared to placebo.The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide.

The full data will be presented at an upcoming scientific meeting. Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission for marketing authorization application. As a rule, Orion will provide information on the progress of the marketing authorization application process in a press release or in its financial reports. Darolutamide has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment in men with nmCRPC.

The ARAMIS trial

Commenced in 2014, the ARAMIS trial evaluated the efficacy and safety of darolutamide in patients with non-metastatic castration-resistant prostate cancer who are currently being treated with androgen deprivation therapy (ADT) as standard of care and are at risk of developing metastatic disease. In the double-blind, placebo-controlled trial, more than 1,500 patients were randomized to receive 600 mg of darolutamide or matching placebo twice a day. The primary endpoint was metastasis-free survival, defined as time between randomization and evidence of metastasis or death from any cause.

Financial terms

Darolutamide was developed jointly by Orion and Bayer, and the partnership was announced in a stock exchange release on 2 June 2014. Bayer has covered the majority of the darolutamide development costs. According to the agreement, Bayer has the right to commercialize darolutamide globally while Orion has the option of co-promoting the product in Europe. In addition, Orion will manufacture the product for global markets.

Orion is eligible to receive milestone payments from Bayer upon first commercial sale of darolutamide as follows:

EUR 45 million upon first commercial sale in the United States
EUR 20 million upon first commercial sale in the EU
EUR 8 million upon first commercial sale in Japan

Besides milestone payments, Orion will also receive tiered royalties on the product sales, which will be approximately 20 percent, including production revenue. With sales increase, royalties may increase slightly. Orion also has the possibility to receive one-off payments from Bayer if certain sales targets are met.

In addition to the completed ARAMIS trial, Orion and Bayer have an ongoing phase III clinical trial (ARASENS) which evaluates the safety and efficacy of darolutamide in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Expected to be completed in 2022, there are no separate milestone payments related to the ARASENS trial.

"Prostate cancer is the second most commonly diagnosed malignancy in men in worldwide, and approximately 70 percent of patients have the non-metastatic form of the disease. While conventional hormone therapy is effective in the treatment of non-metastatic cancer, the efficacy is often eventually lost as the sole form of treatment. Additional treatment options in the early stages of the cancer that delay the time to metastases with a manageable safety profile are long awaited. They are significant for the patient’s overall well-being," says Christer Nordstedt, Senior Vice President, Research and Development at Orion.

BeiGene Announces Acceptance of its New Drug Application in China and Top-Line Pivotal Data for Zanubrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

On October 26, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the acceptance by the China National Medical Products Administration (NMPA) of a new drug application (NDA) for zanubrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, BeiGene, OCT 24, 2018, View Source;p=RssLanding&cat=news&id=2373150 [SID1234530153]). Zanubrutinib was discovered in BeiGene’s research facilities in Beijing, China, and is being developed globally by BeiGene as a monotherapy and in combination with other therapies to treat various hematologic malignancies. In August, the NMPA accepted BeiGene’s first NDA for zanubrutinib for the treatment of patients with R/R mantle cell lymphoma (MCL).

"Our team has made three NDA submissions in China this year, including two for zanubrutinib and one for tislelizumab, our investigational anti-PD-1 antibody. We are hopeful that these submissions, if approved, could further transform BeiGene as well as bring important new treatment options to cancer patients," commented John Oyler, co-founder, CEO and Chairman of BeiGene.

"We are delighted that the submission for zanubrutinib in patients with relapsed/refractory CLL/SLL was accepted by the NMPA in China, and we are excited to announce the top-line pivotal data for zanubrutinib in these patients, which demonstrated a high overall response rate of 80 percent despite a relatively short follow-up. These results in China are also consistent with the data from our global studies," said Dr. Xiaobin Wu, General Manager of China and President of BeiGene, Ltd.

The NDA is supported by an extensive clinical, non-clinical and chemistry, manufacturing and control (CMC) data package, including the results from a 91-patient single-arm pivotal Phase 2 study in Chinese patients with R/R CLL/SLL treated with zanubrutinib, dosed at 160 mg orally twice daily. An independent review of response data from this study, with a data cut-off of June 15, 2018 and a median follow-up of 9.1 months, showed an overall response rate (ORR) of 80 percent, inclusive of complete response (2%), partial response (39%), and partial response with lymphocytosis (40%). The median duration of response has not been reached, as a majority of the responders remain in a response. The safety profile was consistent with previously reported clinical data for zanubrutinib. Updated data with additional follow-up of the patients in the study will be submitted to the NMPA as an additional document of the NDA and are planned to be presented at an upcoming medical conference.

Zanubrutinib was recently granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Waldenström macroglobulinemia (WM). BeiGene plans to submit an NDA to the FDA for zanubrutinib as a potential treatment for patients with WM in the first half of 2019 based on results from a global Phase 1 study.

Zanubrutinib is being evaluated in a broad global registration program, including a fully enrolled Phase 3 clinical trial in patients with WM, comparing zanubrutinib with ibrutinib, the currently approved BTK inhibitor for WM. Zanubrutinib is also being studied in comparison to bendamustine/ rituximab in a Phase 3 clinical trial in patients with previously untreated CLL/SLL, as well as in a pivotal randomized Phase 2 trial in combination with GAZYVA (obinutuzumab) in patients with R/R follicular lymphoma. In China, besides the pivotal Phase 2 trials in R/R MCL and R/R CLL/SLL, BeiGene has completed enrollment in a pivotal Phase 2 clinical trial in patients with WM. BeiGene also plans to initiate a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/ SLL.

About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of non-Hodgkin lymphoma, a type of blood cancer, that arise from B lymphocytes. CLL and SLL are essentially the same disease, with the only difference being the location where the cancer primarily occurs.i When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL.ii

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.

Inovio Pharmaceuticals to Report Third Quarter 2018 Financial Results on November 8, 2018

On October, 26 2018 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported that it will host a conference call and live webcast to report its 2018 third quarter financial results on Thursday, November 8, 2018 at 4:30 p.m. ET (Press release, Inovio, OCT 24, 2018, View Source [SID1234530154]).

A live and archived version of the audio presentation will be available online at View Source This is a listen-only event but will include a live Q&A with analysts.

A replay of the conference call will be accessible two hours after the call at 877-481-4010 (domestic) or 919-882-2331 (international) using replay ID 39603.