On June 5, 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 the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to momelotinib, a JAK1, JAK2 and ACVR1 inhibitor, for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor (Press release, Sierra Oncology, JUN 5, 2019, View Source [SID1234536903]).

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"Fast Track designation for momelotinib highlights the serious and significant unmet needs of patients with myelofibrosis who have previously received a JAK inhibitor. These patients typically suffer from uncontrolled constitutional symptoms, progressively worsening anemia often resulting in transfusion dependency, and enlarged spleens. Fast Track also recognizes the absence of FDA-approved treatments for these patients and that momelotinib has the potential to address their unmet needs," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "We look forward to continuing to work closely with the FDA as we launch and conduct the MOMENTUM Phase 3 trial of momelotinib, with the goal of bringing this important therapy to patients expeditiously."

"We are very pleased that momelotinib has been granted Fast Track designation by the FDA, which further reflects the collaborative and constructive dialogue we have had with the Agency concerning the advancement of momelotinib towards potential registration," said Dr. Nick Glover, President & CEO of Sierra Oncology.

About FDA Fast Track Designation:
The Fast Track program facilitates the expedited development and review of new drugs or biologics that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Fast Track designation allows for frequent communication and interactions with the review team at the FDA throughout the drug development and review process, with the goal of providing faster drug approval and greater patient access.

A drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent written communication from FDA about such things as the design of proposed clinical trials
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed.
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.
Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the MOMENTUM Phase 3 study.

Momelotinib Analyst & Investor Conference Call
The company will be hosting an Analyst and Investor conference call at 6:00 am 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.

Sierra Jefferies Presentation
Dr. Nick Glover, President and Chief Executive Officer, will present an overview of the company and updates concerning its clinical stage drug candidates, momelotinib and SRA737, at 8:00 am ET on Wednesday, June 5, 2019 at the Jefferies Global Healthcare Conference being held in New York.

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 5, 2019 CStone Pharmaceuticals (CStone; HKEX: 2616) reported that it has received approval to initiate clinical development in China of CS1001 in combination with BLU-554 (CS3008) in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) (Press release, CStone Pharmaceauticals, JUN 5, 2019, View Source [SID1234552603]). The trial is a multi-center, open-label, and multi-dose Phase Ib/II study that aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy of the combination in advanced HCC.

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In 2015, there were approximately 326,000 deaths caused by liver cancer in China, making it the second leading cause of cancer death. HCC accounts for approximately 85-90% of all liver cancer cases and is the sixth most common cancer worldwide, with more than half the new cases and deaths every year occurring in China. Currently, advanced HCC represents a significant unmet need for both patients and physicians, with limited approved therapies.

CS1001 is a proprietary anti-PD-L1 monoclonal antibody developed by CStone, and one of the company’s three backbone immuno-oncology products. Currently, CS1001 is being investigated for the treatment of lung cancer, gastric cancers, and other advanced malignancies. In a Phase Ia study, CS1001 was well-tolerated and demonstrated anti-tumor activity with partial responses observed in a number of tumor types.

BLU-554 is a potent and highly selective inhibitor of fibroblast growth factor receptor 4 (FGFR4) discovered by CStone’s partner Blueprint Medicines. In previously presented data from an ongoing Phase I trial for the treatment of advanced HCC patients with aberrant fibroblast growth factor 19 (FGF19)-FGFR4 pathway activation, BLU-554 monotherapy was generally well-tolerated and demonstrated encouraging anti-tumor activity. The U.S. Food and Drug Administration has granted orphan drug designation to BLU-554 for the treatment of HCC.

In June 2018, CStone entered into an exclusive collaboration and license agreement with Blueprint to develop and commercialize three therapeutic candidates, including BLU-554, in mainland China, Hong Kong, Macau and Taiwan. Blueprint retains development and commercial rights to the three licensed therapeutic candidates in the rest of the world.

Dr. Frank Jiang, Chairman and CEO of CStone, commented: "One of CStone’s missions is to develop novel therapies to address important unmet needs created by highly prevalent and difficult-to-treat cancers in China. Combination therapy and precision medicine are the core strategies of our pipeline. Through our partnership with Blueprint, we have already initiated a China clinical program with BLU-554 as a monotherapy for HCC earlier this year, which is part of an ongoing global study. We expect the combination of BLU-554 with CS1001 can offer an important additional treatment option for this challenging disease."

"Emerging clinical data have shown encouraging results in HCC by combining immunotherapies with targeted therapies that are active as single agents. The combination of CS1001 and BLU-554 represents a great example of such an approach and a potential first-line treatment strategy for advanced HCC with FGF19-FGFR4 activation. We will rapidly advance the clinical development of this program to further explore these two promising drug candidates in combination," noted Dr. Archie Tse, Chief Translation Medical Officer of CStone.

About BLU-554

BLU-554 is an orally available, potent, irreversible inhibitor of FGFR4. BLU-554 was specifically designed by Blueprint Medicines to inhibit FGFR4 with exquisite selectivity, thereby sparing the paralogs FGFR1, FGFR2 and FGFR3. Blueprint Medicines is developing BLU-554, an investigational medicine, for the treatment of patients with FGFR4-activated HCC. Blueprint Medicines estimates that approximately 30 percent of patients with HCC have tumors with aberrantly activated FGFR4 signaling.

About CS1001

CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. Authorized by the U.S.-based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, potentially representing a unique advantage over similar drugs.

CS1001 has completed a dose-escalation Phase Ia study in China. In a Phase Ia study, it demonstrated good tolerability and antitumor activity. CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for several tumor types.

On June 5, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported the publication of two articles highlighting the potential of TG4001 and TG6002, two clinical-stage products, that are expected to generate new clinical data in H2 2019 (Press release, Transgene, JUN 5, 2019, View Source [SID1234536904]).

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TG4001 in Gynecologic Oncology

The data confirm the potential of TG4001 (Tipapkinogen Sovacivec), administered as a monotherapy, to treat precancerous HPV-induced lesions (cervical intraepithelial neoplasia – CIN2/3).

These clinical results, with a 30-month follow up, are highly supportive of the ongoing development of TG4001 in combination with avelumab in HPV-positive cancers, including head and neck carcinomas (NCT

03260023), for which efficacy data are expected in H2 2019.

Of the 129 women randomized to TG4001 and 63 to placebo, complete resolution1 was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 high-risk HPV types assayed (24% vs. 10%, p < 0.05).
Irrespective of baseline HPV infection, viral DNA clearance2 was higher in the vaccine group compared to placebo (p < 0.01).
TG4001 was well tolerated with the most common adverse events being injection site reactions.
Ref: The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up, D.M. Harper, et al., Gynecologic Oncology –

View Source

TG6002 in Molecular Therapy Oncolytics

Transgene provides detailed preclinical data on its oncolytic virus TG6002. Based on an optimized Copenhagen strain of vaccinia virus, TG6002 displays a proprietary double gene deletion (TK-RR-) and a patented FCU1 gene, that allows the production of chemotherapy (5-FU) directly in the tumor.

TG6002 is currently being evaluated in a Phase 1/2 study patients with colorectal cancer (NCT

03724071).

TG6002 has an improved safety and efficacy profile and has shown to selectively replicate in tumor cells.
Several models highlight the promising activity of the oncolytic virus, particularly in colorectal carcinoma models.
Ref: The Enhanced Tumor Specificity of TG6002, an Armed Oncolytic Vaccinia Virus Deleted in Two Genes Involved in Nucleotide Metabolism, J. Foloppe, et al., Molecular Therapy Oncolytics –

View Source

On June 5, 2019 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 that the company will present at the Goldman Sachs 40th Annual Global Healthcare Conference in Rancho Palos Verdes, CA (Press release, BeiGene, JUN 5, 2019, View Source [SID1234536907]). The presentation is scheduled for 3:20 p.m. PDT on Wednesday, June 12, 2019.

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A live webcast can be accessed from the investors section of BeiGene’s website at View Source An archived replay will be available for 90 days following the event.

On June 5, 2019 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that the company has entered into an agreement with Merck KGaA, Darmstadt, Germany, a leading science and technology company, which operates in the US and Canada as EMD Serono, and Pfizer Inc. (NYSE: PFE) (Press release, Oncolytics Biotech, JUN 5, 2019, View Source [SID1234536908]). The agreement is to co-develop pelareorep in combination with paclitaxel and avelumab*, a human anti-PD-L1 antibody, for the treatment of hormone-receptor positive, human epidermal growth factor 2-negative (HR+ / HER2-) metastatic breast cancer. Oncolytics and Pfizer will share costs associated with the phase 2 clinical trial.

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"Our co-development agreement with Merck KGaA, Darmstadt, Germany and Pfizer reflects a growing interest in the potential synergistic effect of oncolytic viruses and immune checkpoint inhibitors and provides yet another point of validation for our technology," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech. "We believe pelareorep has broad applicability to boost the effectiveness of a range of checkpoint inhibitors across multiple cancer indications. We are excited to work with Merck KGaA, Darmstadt, Germany, and Pfizer and look forward to quickly developing the program to evaluate the efficacy and safety in metastatic breast cancer and potentially examining pelareorep in combination with other immunotherapies."

"We look forward to working with Oncolytics to assess the potential synergies of avelumab with their oncolytic virus platform to treat metastatic breast cancer." said Chris Boshoff, M.D., Ph.D., Senior Vice President and Chief Development Officer, Oncology, Pfizer.

"Through our collaboration with Oncolytics, we continue to advance our strategy to develop innovative immunotherapy combinations tackling the most challenging cancers," said Kevin Chin, Vice President, Global Clinical Development, Immuno-Oncology at the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono.

The study known as BRACELET-1 (BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti-PD-L1 and Paclitaxel) is an open label study that will enroll 45 patients into three cohorts with 15 patients per cohort: paclitaxel alone, paclitaxel in combination with pelareorep and paclitaxel in combination with both pelareorep and avelumab. The study will examine the expression of immune-related biomarkers to identify changes in T cell clonality between pre-treatment and on-therapy biopsies to confirm our previously identified biomarker and is designed to assess efficacy in terms of overall response rate at week 16 per RECIST 1.1 and iRECIST. The safety of the combination will also be evaluated. During the period of the study and for 90 days after a pre-determined interim analysis, Oncolytics may exclusively develop pelareorep in HR+ / HER2- metastatic breast cancer with Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of hormone receptor-positive, human epidermal growth factor 2-negative (HR+ / HER2-) metastatic breast cancer and has not been demonstrated to be safe and effective for this use. There is no guarantee that avelumab will be approved for HR+ / HER2- metastatic breast cancer by any health authority worldwide.

About avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.3-5 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.5-7 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab Approved Indications

Avelumab (BAVENCIO) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO©) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions [which can be severe and have included fatal cases]), infusion-related reactions, major adverse cardiovascular events (MACE), and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Additional common adverse reactions reported in patients receiving BAVENCIO in combination with axitinib include hypertension, mucositis, palmar-plantar erythrodysesthesia, dysphonia, hypothyroidism, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Clinical chemistry and hematology laboratory value abnormalities have been reported including but not limited to grade 3-4 lymphopenia, anemia, elevated cholesterol and liver enzymes.

For full Prescribing Information and Medication Guide for BAVENCIO, please see www.BAVENCIO.com.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.