On June 4, 2019 Oncoceutics, Inc. reported a publication in the Journal for ImmunoTherapy of Cancer demonstrating ONC201 immunostimulatory activity in advanced cancer patients when given the recommended phase II dose (RP2D) of 625 mg orally every one week (Press release, Oncoceutics, JUN 4, 2019, View Source [SID1234558353]). The publication, which describes a Phase I trial conducted by Mark Stein, MD, at the Rutgers Cancer Institute of New Jersey (CINJ) to evaluate weekly oral administration of the company’s lead compound ONC201, also confirmed previous studies, which demonstrated that the drug was well-tolerated. Weekly dosing stimulated intratumoral infiltration and activation of natural killer (NK) cells. The immune stimulatory effects that were observed under weekly dosing were significantly improved over a schedule that used ONC201 every 3 weeks.

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These results confirm findings reported in 2018 in the Journal of Clinical Investigation in a study led by Wafik El-Deiry, MD, PhD, FACP that described intratumoral NK cell accumulation and activation in preclinical models. Dr. El-Deiry is the Director of the Joint Program in Cancer Biology at Brown University and the Lifespan Cancer Institute, Associate Dean for Oncologic Sciences at the Warren Alpert Medical School, Brown University, and the Scientific Founder of Oncoceutics.

In addition, the new study showed that weekly oral administration of ONC201 did not result in dose-limiting toxicities, discontinuations, or dose modifications. No Grade 3/4 side effects occurred that were attributed to study drug. The pharmacokinetic profile of weekly ONC201 exceeded preclinical therapeutic thresholds and resulted in intratumoral integrated stress response activation and apoptosis. This was consistent with previously published studies, which also demonstrated that ONC201 was well-tolerated by cancer patients.

"Immune activation further explains the durable tumor regressions reported with ONC201," said Varun Vijay Prabhu, PhD, Associate Vice President of R&D at Oncoceutics, "The safety profile of ONC201 has allowed dose intensification with weekly administration."

"NK cell activation and other immune stimulatory effects contribute to the overall anti-tumor effect of ONC201 and provide a rationale for combination with immune-checkpoint therapies," said Dr. El-Deiry. "Based on these findings, we have worked towards initiating a Phase Ib/II trial to evaluate ONC201 in combination with nivolumab."

On June 04, 2019 Bayer and Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies to degrade disease-causing proteins, reported an agreement to leverage Arvinas’ novel PROTAC protein degrader technology to develop new human therapeutics for patients with cardiovascular, oncological, and gynecological diseases (Press release, Arvinas, JUN 4, 2019, View Source [SID1234645312]). In addition, Bayer and Arvinas will jointly launch a new company to leverage Arvinas’ PROTAC technology for agricultural applications. The overall series of arrangements includes over $110 million in upfront cash and committed funding for the human disease collaboration, the agricultural joint venture, and a direct equity investment by Bayer in Arvinas.

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The multi-faceted deal will extend the application of targeted protein degradation to new therapeutic areas and outside human biology. It leverages Arvinas’ expertise in targeted protein degradation, a field the company has led since its founding in 2013, and Bayer’s decades of experience in developing both human therapies and innovative, sustainable agricultural technologies.

"As the first company founded around targeted protein degradation, we’ve been excited about the potential to improve the lives of patients since our inception," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "However, we’ve known that the potential of this technology could be broader than drug development. Through these transactions, not only do we plan to expand our reach into new therapeutic areas, but we and Bayer expect to be the first to apply this approach to agriculture, working to safely and efficiently feed the world’s growing population. It’s a natural next step in our commitment to improving human health."

"With our unique position as a leading company in both Crop Science and Pharmaceuticals, we see a great opportunity to partner with the pioneer of the PROTAC technology, to advance this technology as quickly as possible to deliver future solutions for sustainable agriculture and innovative medicines for patients," said Kemal Malik, Bayer Board member for Innovation.

Pharmaceutical Collaboration and Equity Investment
Bayer and Arvinas will collaborate to seek to develop a series of novel product candidates for diseases with serious unmet need. Arvinas will receive an upfront payment and committed R&D funding, as well as a direct equity investment in Arvinas. Combined, these committed funds exceed $60 million. Bayer will own the rights to novel lead structures generated in the collaboration. As programs progress through research, development, and commercialization, Arvinas is also eligible to receive development milestones of over $685 million and commercial royalties ranging from the mid-single digits to the low double-digits.

Agricultural Joint Venture
In launching a joint venture (JV), Bayer and Arvinas are investing in one of the greatest challenges facing the world: feeding the growing global population. PROTAC targeted protein degraders have the potential to address resistance mechanisms in plants to existing agricultural solutions, with solutions to control weeds, insects, and disease by leveraging the selectivity and other features of PROTAC protein degraders. The JV will be committed to leveraging Arvinas’ PROTAC protein degrader technology to create innovative, safe, and sustainable agricultural products. The JV will be supported by intellectual property and over $55 million in committed funding from Bayer, and by technology and intellectual property from Arvinas. Bayer and Arvinas will equally share governance and equity ownership of the JV.

Arvinas Financial Guidance
The closing of this multi-faceted deal with Bayer, including the pharmaceutical collaboration, direct equity investment, and agricultural JV, will lead to updated financial guidance for Arvinas. With the closing of the transaction, which is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions, current cash and investments are expected to be sufficient for planned operations into the second half of 2021.

On June 4, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that it has obtained regulatory clarity with the U.S. Food and Drug Administration (FDA) concerning the design of a Phase 3 clinical trial for momelotinib intended to support potential registration of this differentiated drug candidate for the treatment of previously JAK inhibitor treated myelofibrosis patients (Press release, Sierra Oncology, JUN 4, 2019, View Source [SID1234536864]). Following receipt of this clarity, Sierra also announced the design of the MOMENTUM Phase 3 clinical trial in myelofibrosis, planned for launch in Q4 2019.

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"We have held productive discussions with regulators in the US and EU, presenting a holistic analysis of momelotinib’s compelling array of positive efficacy and safety data observed in the two previously completed SIMPLIFY Phase 3 clinical studies, along with our strategy to conduct an additional Phase 3 trial intended to support momelotinib’s potential registration," said Dr. Nick Glover, President and CEO of Sierra Oncology. "We have been exceedingly pleased with the collaborative nature of these discussions which have culminated in alignment on the path to potential registration for momelotinib. Moreover, we have received constructive input that ensures that the design of the MOMENTUM Phase 3 study has the potential to generate compelling and persuasive clinical data capable of satisfying regulatory requirements."

"Momelotinib has consistently demonstrated clinically relevant benefits on the three hallmarks of myelofibrosis: symptoms, anemia and spleen enlargement," noted Dr. Srdan Verstovsek, MD, PhD, Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas. "I have been involved in the development of momelotinib for many years, and I am very pleased to be named Chief Investigator of the MOMENTUM Phase 3 study. In my opinion, a good proportion of myelofibrosis patients in the second line setting would be candidates for momelotinib treatment due to its potential ability to improve both quality of life and anemia in a significant number of patients. As a myelofibrosis clinician, I can attest that we desperately need more treatment options that offer an array of distinct benefits for our patients. I look forward to momelotinib potentially becoming an important addition to the armamentarium in the treatment of myelofibrosis."

"We have designed MOMENTUM in order to generate highly persuasive clinical data with the potential to convincingly demonstrate momelotinib’s meaningful benefits on symptoms, anemia and spleen in the population of patients previously treated with a JAK inhibitor, as supplemented by both top-line and post hoc analyses of the prior SIMPLIFY Phase 3 datasets," said Dr. Barbara Klencke, Chief Development Officer, of Sierra Oncology. "We have outlined a robust, tractable study that we plan to launch in Q4 2019 and that we anticipate will yield top-line clinical data in Q4 2021."

About MOMENTUM Phase 3 Clinical Trial:
A Randomized, Double-Blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic Subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera (PV) Myelofibrosis, or Post Essential Thrombocythemia (ET) Myelofibrosis who were Previously Treated with JAK Inhibitor Therapy.

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in Q4 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic and have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05). Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: > 90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (> 90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical function.
About Dr. Srdan Verstovsek, Chief Investigator of the MOMENTUM Phase 3 trial:
Dr. Srdan Verstovsek is Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston. Dr. Verstovsek is a world-renowned physician-scientist, and a leading global authority on the treatment of myelofibrosis. His clinical and translational research is focused on understanding the biology of and developing new therapies for myeloproliferative neoplasms (MPNs). He has been Principal investigator for more than 50 clinical trials testing novel therapies for patients with MPNs, and has published more than 400 peer-reviewed manuscripts. He is the recipient of numerous awards including the Celgene 2010 Young Investigator Award, 7th Annual Irwin H. Krakoff Award for Excellence in Clinical and the Distinguished Lecturer Award from the Society of Hematologic Oncology and the Otis W. and Pearl L. Walters Faculty Achievement Award in Clinical Research by MD Anderson Cancer Center. He was made a Member of The American Society for Clinical Investigation in recognition of his contributions as a physician-scientist.

Momelotinib Analyst & Investor Conference Call
The company will be hosting an Analyst and Investor conference call at 6:00am ET on Wednesday, June 5, 2019, to discuss next steps for momelotinib.

Domestic (Toll Free- US): 1-800-239-9838
International (Toll): 1-323-794-2551
Conference ID: 8101895
Webcast Link: www.sierraoncology.com
Direct Link: View Source

Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. An archive of the presentation will be accessible after the event through the Sierra Oncology website.

About Momelotinib
Momelotinib, Sierra’s lead drug candidate, is a potent, selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a differentiated therapeutic profile in myelofibrosis encompassing robust constitutional symptom improvements, a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, and comparable spleen control to ruxolitinib. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including more than 800 subjects treated for myelofibrosis. Momelotinib is covered by patents anticipated to provide potential exclusivity to 2040 in the U.S.

On June 4, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II variation to the European Medicines Agency (EMA) seeking approval of ERLEADA (apalutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of extent of disease or prior docetaxel treatment history (Press release, Johnson & Johnson, JUN 4, 2019, View Source [SID1234536881]). The submission is based on findings from the Phase 3 TITAN study which were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published online in The New England Journal of Medicine.1,2

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The submission to the EMA follows the submission of supplemental registration dossiers to the U.S. Food and Drug Administration (FDA) on 29th April 2019 and to the Japanese Ministry of Health, Labour and Welfare (MHLW) on 31st May 2019 seeking approval of a new indication for apalutamide for the treatment of patients with mHSPC.3,4

"Today’s application seeking to expand the approval of apalutamide for the treatment of patients with mHSPC marks an important step in our continued focus and commitment to bring innovative medicines forward in the treatment of prostate cancer," said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. "We look forward to working with the EMA to expand access to this next-generation androgen receptor inhibitor for those patients who may benefit from this treatment in the future."

Results from the Phase 3 TITAN study showed patients with mHSPC, treated with apalutamide plus androgen deprivation therapy (ADT) significantly extended overall survival (OS) compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; P=0.0053).2 In both study arms, median OS was not reached.2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).1 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.2

Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The incidence of Grade 3/4 AEs for apalutamide plus ADT, versus placebo plus ADT were similar (42 percent vs 41 percent).2 The most common Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).2 Additional reported Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).2 Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.1 Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27 percent vs 9 percent, respectively).2

In Europe, apalutamide is currently approved for use in adults with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

ENDS

About the TITAN Study1,2

TITAN is a Phase 3 randomised, placebo-controlled, double-blind study in men with mHSPC regardless of extent of disease or prior docetaxel treatment history. The study included 1,052 patients in intention-to-treat (ITT) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either apalutamide (240 mg) plus continuous androgen deprivation therapy (ADT) (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017. The study included mHSPC patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mHSPC. Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity. An independent data-monitoring committee was commissioned by the sponsor to monitor safety and efficacy before unblinding and make study conduct recommendations. Dual primary endpoints of the study were OS and rPFS. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to second progression-free survival and time to symptomatic progression. For additional study information, visit ClinicalTrials.gov.

About ERLEADA

ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

About Metastatic Hormone-Sensitive Prostate Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC), also referred to as metastatic castration sensitive prostate cancer (mCSPC) refers to prostate cancer that still responds to androgen deprivation therapy (ADT) and has spread to other parts of the body.7 Patients with mHSPC tend to have a poor prognosis, with a median OS of less than five years, underscoring the need for new treatment options.8,9,10

On June 4, 2019 VBL Therapeutics (Nasdaq: VBLT), reported that Dr. Dror Harats, CEO will deliver a company presentation today at the 2019 BIO International Convention in Philadelphia (Press release, VBL Therapeutics, JUN 4, 2019, View Source [SID1234536865]). The presentation will include a discussion on the recent VB-111 progress, including data presented earlier this week at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting. The presentation will be also available to the investor audience by webcast.

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2019 BIO International Convention – Presentation Details

Date: June 4, 2019
Time: 3:30 pm EDT
Presentation Room: Theater 2
Location: Philadelphia Convention Center
Webcast: 2019 BIO International Convention Webcast

About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in the OVAL potential-registration Phase 3 pivotal trial for ovarian cancer (ClinicalTrials.gov Identifier: NCT03398655). VB-111 has received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. In addition, VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970). VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission.