Month: April 2017

Bristol-Myers Squibb Announces Results from CheckMate -143, a Phase 3 Study of Opdivo (nivolumab) in Patients with Glioblastoma Multiforme

On April 3, 2016-Bristol-Myers Squibb Company (NYSE:BMY) reported that CheckMate -143, a randomized Phase 3 clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme (GBM), did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy (Press release, Bristol-Myers Squibb, APR 3, 2017, View Source [SID1234518425]). These data will be presented on May 7, 2017 at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland.

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"GBM is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses," said Fouad Namouni, M.D., head of Oncology Development and head of Medical, Bristol-Myers Squibb. "We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our Immuno-Oncology agents can potentially improve outcomes for these patients."

CheckMate -143 was the first randomized clinical trial in GBM with a PD-1 checkpoint inhibitor. BMS has two first-line GBM clinical trials, CheckMate -498 and CheckMate -548, evaluating the combination of Opdivo with radiation therapy with or without temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated and methylated patients. These trials are moving forward as planned.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

8-K – Current reIntelGenx and Tetra Bio-Pharma Announce the Signing of a Definitive Agreement for the Development and Commercialization of a Dronabinol XL Tabletport

On April 3, 2017 IntelGenx Corp. ("IntelGenx") (TSXV: IGX) (OTCQX: IGXT) and Tetra Bio-Pharma Inc. ("Tetra") (CSE: TBP) (OTCPINK: GRPOF), reported the signing of a definitive agreement for the development and commercialization of a drug product containing the cannabinoid Dronabinol (the "Product") for the management of anorexia and cancer chemotherapy-related pain (Press release, IntelGenx, APR 3, 2017, View Source [SID1234518424]). This definitive agreement follows the binding term sheet between the two companies that was announced on February 9, 2017.

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Pursuant to the definitive agreement, Tetra has exclusive rights to sell the Product in North America, with a right of first negotiation for territories outside of the United States and Canada. Tetra will make an upfront payment to IntelGenx, in addition to set future milestone and royalty payments, based on the completion of an efficacy study, approvals from the U.S. Food and Drug Association ("FDA") and Health Canada, and the commercial launch of the Product. IntelGenx will be responsible for the research and development of the Product, including clinical studies, and will develop the product as an oral mucoadhesive tablet based on its proprietary AdVersa controlled-release technology. Tetra will be responsible for funding the product development, and will own and control all regulatory approvals, including the related applications, and any other marketing authorizations. Tetra will also be responsible for all aspects of commercializing the Product.

"The U.S. cancer pain market is expected to reach $5 billion in 2018, and the quick growing medical cannabis industry is poised to capture a signature portion of that opportunity," said Dr. Horst G. Zerbe, President and CEO of IntelGenx. "We are pleased to be working with Tetra to bring this much-needed cannabinoid product to North American patients suffering from anorexia and cancer chemotherapy-related pain."

"We are pleased to announce the signing of the definitive agreement with IntelGenx and look forward to working very hard with them to bring this much-needed product to patients suffering from cancer pain," said Andre Rancourt, CEO of Tetra. "The execution of this agreement is just the beginning for Tetra as we look forward to aggressively concluding future agreements as we build a leading bio-pharmaceutical organization focused on developing medicinal cannabis as pharmaceutical drugs."

Background Information

There are many clinical problems associated with the use of currently available form of Dronabinol in patients with anorexia and cancer chemotherapy-related pain. It has been demonstrated that psychoactive drugs exert their euphoria, and other psychoactive effects, when the blood levels of the drug rapidly increase. The pharmacokinetic profile of tetrahydrocannabinol ("THC") and its metabolite increases the abuse potential of cannabinoids like Dronabinol. The significant advantage of an oral mucoadhesive tablet based on IntelGenx’ proprietary AdVersa controlled-release technology is that it can be adjusted to achieve a predetermined drug release pattern by increasing the residence time, promoting intimate contact with the mucosal tissue and increasing the bioadhesive properties of the dosage form. It is believed that, by deploying this technology in the controlled-release of THC, a longer time release of the drug will be achieved and, thereby, a rapid increase in the blood will be avoided. There will also potentially be improved bioavailability and reduced gastro-intestinal side effects, making a sustained-release THC product a promising alternative in the battle for the reduction of opioids in patients with chronic pain.

Five Prime Presents Preclinical Research Data on CSF-1R and PD-1 Blockade at the 2017 AACR Annual Meeting

On April 3, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that a poster featuring preclinical data related to Five Prime’s CSF-1R antibody, cabiralizumab (FPA008), was presented today at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, D.C (Press release, Five Prime Therapeutics, APR 3, 2017, View Source [SID1234518423]). The poster titled "Antibody-Based Inhibition of CSF-1R as a Component of Combination Immunotherapy in Preclinical Models" is available at View Source

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"These preclinical findings suggest that the surrogate antibody for FPA008 significantly reduces tumor growth in murine syngeneic tumor models when administered alone and when administered in combination with a PD-1 antibody," said Kevin Baker, Ph.D., Senior Vice President of Development Sciences at Five Prime. "These findings support previous preclinical data that served as the basis for our Phase 1a/1b clinical trial that we are running in collaboration with Bristol-Myers Squibb (BMS) to investigate the use of cabiralizumab in combination with nivolumab (anti-PD-1, OPDIVO) in six different tumor types."

The colony stimulating factor 1 receptor (CSF-1R) signaling pathway promotes tumor progression via the recruitment, differentiation, and survival of immuno-suppressive, M2 polarized, tumor-associated macrophages (TAMs). Five Prime has developed cabiralizumab (FPA008), an IgG4 antibody against CSF-1R that blocks the ability of both CSF-1 and IL-34 to bind and activate this receptor, thereby modulating the immune response to tumorigenesis.

Five Prime has identified alterations in the tumor microenvironment that occur upon CSF-1R inhibition, including significant reduction of immunosuppressive M2 TAMs and an increase in tumor PD-L1 expression. Notably, when dosing in combination, the blockade of CSF-1R and PD-1/PD-L1 results in a significant increase in CD8+ T cells within the tumor. The results show that, when added to PD-1/PD-L1 blockade, the surrogate antibody for FPA008 can significantly enhance anti-tumor efficacy.

Five Prime Presents Data on Unique Immuno-Oncology Discovery Research at the 2017 AACR Annual Meeting

On April 3, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that a poster featuring data related to Five Prime’s unique discovery platform was presented today at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, D.C (Press release, Five Prime Therapeutics, APR 3, 2017, View Source [SID1234518422]). The poster titled "Identification of Novel T Cell Co-Inhibitory and Co-Stimulatory Receptors from Screening a Comprehensive Library of Extracellular Proteins" is available at View Source

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"We have generated a comprehensive library of essentially all human extracellular proteins and have used this library to screen for new agents that modulate the function of various immune cell subsets," said Luis Borges, Ph.D., Senior Vice President of Research at Five Prime. "Taken together, we have developed robust in vitro and in vivo platforms that allow us to discover new immuno-oncology targets that we believe will help address the needs of cancer patients who fail to respond to current immunomodulatory therapies."

Five Prime has developed multiple sophisticated in vitro, in vivo, and biophysical assay systems for screening its comprehensive library of human extracellular proteins to identify novel therapeutics that can reprogram immune cells in the tumor microenvironment.

These multiple approaches include:

In vitro screens of primary human effector and regulatory T cells to identify novel proteins that can modulate T cell activation and suppression.
Screening subsets of the discovery library in four distinct syngeneic mouse tumor models (either as single agents, or in combination with checkpoint blockade or a vaccine) to identify targets that can modulate an anti-tumor immune response in vivo.
Performing a combinatorial biophysical screen for extracellular protein-protein interactions within a set of approximately 700 predicted immune-related transmembrane proteins to identify novel receptor-ligand interaction networks.
As a result of these screens that combine data from multiple screening approaches, Five Prime has prioritized a series of new targets for validation and potential generation of novel immuno-oncology therapeutics.

Sierra Oncology Collaborator ICR Reports Preclinical Synthetic Lethality Data for Chk1 Inhibitor SRA737 at AACR

On April 3, 2017 Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response therapeutics for the treatment of patients with cancer, reported that preclinical results for its Chk1 inhibitor, SRA737, were presented on April 2 in a poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held in Washington D.C (Press release, Sierra Oncology, APR 3, 2017, View Source [SID1234518421]). This research was conducted in the laboratory of Professor Paul Workman, Chief Executive and President of The Institute of Cancer Research (ICR), London, UK, and funded by Wellcome.

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"These data demonstrate that inhibition of B-family DNA polymerases, POLA1, POLE and POLE2, combined with inhibition of Chk1, is synthetically lethal in numerous cancer cell lines," noted Professor Workman. "This supports the genetically-driven clinical development strategy Sierra intends to pursue for SRA737. For example, subsets of colon and endometrial cancers with POLE mutations may be sensitive to CHK1 inhibitors as monotherapy. In addition, gemcitabine is known to impair the B-family DNA polymerases, further supporting the rationale for its clinical combination with SRA737."

"The ICR is a world-class cancer research institution and we are fortunate to maintain an ongoing collaborative relationship for the development of SRA737. In particular, the data reported by Professor Workman’s laboratory continues to reinforce the synthetic lethality hypothesis for SRA737, and further validates our approach to developing our lead drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "Appropriate patient selection is critical for clinical success. Fortunately, the biology underlying Chk1’s role in cancer and the DNA Damage Response suggest numerous opportunities where a patient’s specific tumor genetics might be linked to their predicted response to SRA737."

The poster, entitled: "Screening the druggable genome for synthetic lethal interactions with the CHK1 inhibitor PNT737" is available at www.sierraoncology.com. Additional information including full abstracts can be found at www.aacr.org.

About SRA737
SRA737, is a highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), currently being evaluated in two Phase 1 clinical trials in patients with advanced cancer.

The first trial is evaluating SRA737’s potential to induce synthetic lethality as monotherapy. Sierra recently proposed amendments to this trial to prospectively enroll subjects with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition. The study will employ a genetic selection algorithm targeting mutations in TP53, BRCA1, BRCA2, MYC, RAS, or other related genes associated with tumor suppression, oncogenesis, DNA damage repair, and replicative stress. Additionally, Sierra intends to modify the study to assess SRA737’s clinical activity across several cancer indications that harbor these genetic mutations including, for example, cohorts of subjects with 1) previously treated metastatic colorectal cancer; 2) platinum-resistant ovarian cancer; 3) metastatic castration-resistant prostate cancer; 4) advanced non-small cell lung cancer; and 5) advanced head and neck squamous cell carcinoma.

Sierra is currently also evaluating SRA737 in combination with gemcitabine and gemcitabine plus cisplatin. The company intends to modify the design of this clinical trial to expand enrollment in the gemcitabine combination following the completion of dose escalation. Subjects with 1) advanced bladder cancer and 2) advanced pancreatic cancer will be enrolled into genetically-selected dose expansion cohorts, employing a genetic selection algorithm similar to that to be used in the monotherapy protocol.