On January 8, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported it has received a milestone payment from MedImmune as MEDI0457 (formerly called INO-3112 which MedImmune in-licensed from Inovio) in combination with durvalumab (MEDI4736) satisfactorily completed the phase 1 safety review portion of the study and has advanced to the phase 2 efficacy stage of the trial (Press release, Inovio, JAN 8, 2018, View Source [SID1234523010]). As part of a $700 million 2015 license and collaboration agreement, MedImmune, the global biologics research and development arm of AstraZeneca, is evaluating MEDI0457 in combination with durvalumab, its PD-L1 checkpoint inhibitor, in patients with recurrent/metastatic HPV-associated head and neck squamous cancer (HNSCC) in a clinical trial with an estimated enrollment of 50 patients.

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Under the 2015 agreement, MedImmune acquired exclusive rights to Inovio’s MEDI0457 immunotherapy. MEDI0457 targets cancers caused by human papillomavirus (HPV) types 16 and 18 which are responsible for more than 70 percent of cervical pre-cancers and cancers and are involved in the development of other tumors as well such as HNSCC. Within the broader license and collaboration agreement, MedImmune and Inovio will develop two additional DNA-based cancer therapy products not included in Inovio’s current product pipeline, which MedImmune has exclusive rights to develop and commercialize. Inovio will receive development, regulatory and commercialization milestone payments and will be eligible to receive royalties on worldwide net sales for these additional cancer vaccine products.

Dr. Ildiko Csiki, MD, PhD, Inovio Vice President, Clinical Development said, "We are pleased to see this combination study advance to the efficacy portion of the trial. Published preclinical studies suggest that treatment with HPV targeted immunotherapeutic approach in combination with PD-1/PD-L1 inhibition may be synergistic, and potentially increase efficacy of checkpoint inhibitors."

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "Inovio’s primary goal is to become the global leader in HPV-related disease treatment. Along with MEDI’s development of MEDI0457 for HPV-related cancer, Inovio’s VGX-3100, is currently being tested in global phase 3 pivotal trials for cervical pre-cancer as well as a treatment for vulvar and anal pre-cancers caused by HPV. Overall, these products could be well-positioned to comprehensively treat HPV-related diseases across the continuum of HPV infections from pre-cancerous conditions to cancer in both women and men."

In a phase 1 study of MEDI0457 in 22 HPV-positive patients with HNSCC, Inovio has previously demonstrated that MEDI0457 generated robust antigen-specific CD8+ killer T cell responses in both tumor tissue and peripheral blood. One patient in that trial who initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study and subsequently received a PD-1 checkpoint inhibitor. The patient had a sustained complete response after only four doses of a checkpoint inhibitor, and continues on anti PD-1 therapy with no evidence of disease 18 months after initiation of the checkpoint inhibitor.

About MEDI0457 and VGX-3100

MEDI0457 (formerly called INO-3112 (VGX-3100, plus IL-12) which MedImmune in-licensed from Inovio) is under evaluation by MedImmune to treat HPV-associated cancers. Inovio is investigating VGX-3100, a DNA-based immunotherapy for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (phase 3) and vulva (phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

On January 8, 2018 Exelixis, Inc. (NASDAQ: EXEL) reported that it has entered into an exclusive collaboration and license agreement with StemSynergy Therapeutics, Inc., (StemSynergy) for the discovery and development of novel oncology compounds targeting Casein Kinase 1 alpha (CK1α), a component of the Wnt signaling pathway implicated in key oncogenic processes (Press release, Exelixis, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325370 [SID1234523005]). The agreement is part of Exelixis’ ongoing strategy to build an innovative pipeline beyond its two internally-discovered, commercially available compounds, cabozantinib and cobimetinib.

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Under the terms of the agreement, Exelixis will partner with StemSynergy to conduct preclinical and clinical studies with compounds from StemSynergy’s CK1α Activator Program. Exelixis will pay StemSynergy an upfront payment of $3M and up to $3.5M in initial research and development funding. StemSynergy will be eligible for a variety of milestones for the first product to emerge from the collaboration, including preclinical and clinical development and regulatory milestone payments, commercial milestones, as well as single-digit royalties on worldwide sales. Exelixis will be solely responsible for the commercialization of products that arise from the collaboration.

"Supported by revenues from its commercial products and collaborations, Exelixis is on a growth trajectory and now actively focused on augmenting our pipeline both through targeted business development and internal drug discovery activities," said Peter Lamb, Ph.D., Executive Vice President, Discovery Research and Chief Scientific Officer of Exelixis. "CK1α activation is an underexplored and intriguing mechanism for addressing the Wnt/β-catenin axis, a major pathway deregulated in multiple cancers. We look forward to working with StemSynergy to advance this compelling program as we build the next generation of Exelixis medicines."

The CK1α Activator Program is representative of StemSynergy’s focus on treating cancer by targeting developmental processes that are reactivated in cancer cells. The Wnt signaling pathway is a prominent example of this process: the pathway plays an important role in embryonic development, but can support oncogenic processes when deregulated in adult tissues. Activation of β-catenin, a key downstream component of the pathway, is increased in multiple tumors, including a majority of colorectal cancers, where mutations in the APC gene that result in beta-catenin stabilization are prevalent. CK1α Activator Program compounds have been shown to induce degradation of β-catenin and pygopus, another member of the pathway, in preclinical CRC models, and to inhibit the growth of tumors. Importantly, their GI-sparing qualities may help overcome limitations of other approaches targeting the Wnt pathway.

"StemSynergy is developing compounds that can specifically address developmental pathways reactivated in cancer cells to potentially deliver greater benefit to patients," said Anthony J. Capobianco, Ph.D., President and Co-Founder of StemSynergy. "Our CK1α Activator Program has been supported in part by the National Cancer Institute through the SBIR program. With deep drug discovery and development expertise and a proven track record of successfully bringing medicines to market, Exelixis is a natural partner for our CK1α Activator Program as it advances. We look forward to collaborating with the experienced Exelixis team to move the program forward."

On January 8, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, and Mirati Therapeutics (NASDAQ:MRTX), a clinical-stage targeted oncology company, reported an exclusive license agreement for the development, manufacturing and commercialization of Mirati’s sitravatinib in Asia (excluding Japan), Australia, and New Zealand (Press release, BeiGene, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325285 [SID1234523004]). Mirati will retain exclusive rights for the development, manufacturing and commercialization of sitravatinib for the rest of world.

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Sitravatinib is an investigational tyrosine kinase inhibitor that has demonstrated potent inhibition of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET. It is being evaluated by Mirati as a single agent in a Phase 1b expansion trial in patients whose tumors harbor specific genetic alterations in non-small cell lung cancer (NSCLC) and other tumors types. Sitravatinib has shown encouraging interim results in an ongoing Phase 2 trial in combination with nivolumab in NSCLC patients who have progressed after prior treatment with a checkpoint inhibitor.

"We are delighted to enter into this exclusive clinical development and commercialization agreement for sitravantinib and look forward to working with the experienced team at Mirati. Sitravatinib is an exciting compound that has demonstrated a unique tyrosine kinase inhibition profile and promising clinical activity both as a single agent and in combination with a checkpoint inhibitor in non-small cell lung cancer. This collaboration complements our portfolio and will allow us to investigate sitravatinib in combination with tislelizumab, our investigational anti-PD-1 antibody, in China and the rest of the licensed territory," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"We are excited to begin a partnership with BeiGene, which has built a world-class global development organization with a strong presence in Asia-Pacific, as well as an established commercial organization in China. They have demonstrated an ability to enroll patients quickly in a variety of indications which will augment our development capabilities and expand the evaluation of sitravatinib to additional tumor types for patients who are checkpoint inhibitor naïve or who have been previously treated with a checkpoint inhibitor," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer of Mirati Therapeutics.

Under the agreement Mirati will receive an upfront cash payment of $10 million from BeiGene. Additionally, Mirati is eligible to receive up to $123 million of additional payments based upon the achievement of certain development, regulatory and sales milestones as well as significant royalties on future sales of sitravatinib in the licensed territory.

About Sitravatinib

Sitravatinib (MGCD-0516) is a spectrum-selective kinase inhibitor which potently inhibits receptor tyrosine kinases (RTKs) including RET, TAM family receptors (TYRO3, Axl, MER), and split family receptors (VEGFR2, KIT). Sitravatinib is being evaluated as a single agent in a Phase 1b expansion trial enrolling patients that harbor RET, CHR4Q12, and CBL genetic alterations in NSCLC and other tumors.

As an immuno-oncology agent, sitravatinib is being tested in combination with anti PD-1 checkpoint inhibitor nivolumab in NSCLC patients who have progressed after prior treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family receptors may help overcome resistance to checkpoint inhibitor therapy through enhancement of dendric cell-dependent antigen presentation, targeted depletion of immunosuppressive T regulatory cells and myeloid-derived suppressor cells, and conversion of tumor associated macrophages to an immune-enhancing Type I composition, in the tumor microenvironment.

About Tislelizumab (BGB-A317)

Tislelizumab is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for tislelizumab for solid tumors outside of Asia (except Japan).

On January 8, 2018 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on developing novel, best-in-class treatments to address some of the most important unmet patient needs, reported progress in the Company’s pain management and CINV franchises (Press release, Heron Therapeutics, JAN 8, 2018, View Source [SID1234522991]).

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CINV Franchise

SUSTOL Sales. SUSTOL (granisetron) extended-release injection fourth-quarter 2017 net product sales were approximately $10 million, up 16% from third-quarter 2017 net product sales of $8.6 million. SUSTOL full-year 2017 net product sales were approximately $31 million, versus guidance of $25 million to $30 million.
2018 CINV Sales Guidance. Net product sales guidance for full-year 2018 for the CINV franchise is $60 million to $70 million.
Permanent J-Code Now Effective. On January 1, 2018,a product-specific billing code, or permanent J-code, for SUSTOL became available. The new J-code was assigned by the Centers for Medicare and Medicaid Services (CMS) and will help simplify the billing and reimbursement process for prescribers of SUSTOL.
CINVANTI Now Available. In November 2017, the U.S. Food and Drug Administration (FDA) approved the Company’s New Drug Application (NDA) for CINVANTI (aprepitant) injectable emulsion, the first and only polysorbate 80-free intravenous (IV) formulation of a neurokinin-1 (NK1) receptor antagonist indicated for the prevention of acute and delayed CINV. CINVANTI became commercially available in the United States on January 4, 2018.
Pain Management Franchise

Enrollment Complete in Phase 3 Pivotal Trials for HTX-011 in Postoperative Pain. Heron completed enrollment in its two pivotal Phase 3 efficacy studies in bunionectomy and hernia repair. Heron anticipates reporting top-line results in the first half of 2018 and expects to file an NDA with the FDA in the second half of 2018.

"Heron had a strong year in 2017, led by the advancement of the HTX-011 program toward an NDA filing, the success of our commercial team with SUSTOL and the expansion of our CINV franchise with the approval of CINVANTI," said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron. "We expect to build on our momentum in 2018 by reporting top-line pivotal Phase 3 results for HTX-011, filing an NDA for HTX-011 and growing our CINV franchise, which now includes two innovative products."

About HTX-011 for Postoperative Pain

HTX-011, which utilizes Heron’s proprietary Biochronomer drug delivery technology, is an investigational, long-acting, extended-release formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the prevention of postoperative pain. By delivering sustained levels of both a potent anesthetic and a local anti-inflammatory agent directly to the site of tissue injury, HTX-011 was designed to deliver superior pain relief while reducing the need for systemically administered pain medications such as opioids, which carry the risk of harmful side effects, abuse and addiction. The Phase 2 development program for HTX-011 was designed to target the many patients undergoing a wide range of surgeries who experience significant postoperative pain. Heron completed enrollment in its two pivotal Phase 3 efficacy studies in bunionectomy and hernia repair and anticipates reporting top-line results in the first half of 2018 and expects to file an NDA with the FDA in the second half of 2018.

About CINVANTI (aprepitant) injectable emulsion

CINVANTI is indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). CINVANTI is an intravenous formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist. CINVANTI is the first intravenous (IV) formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce CINV in both the acute phase (0 – 24 hours after chemotherapy) and the delayed phase (24 – 120 hours after chemotherapy). CINVANTI does not contain polysorbate 80 or any other synthetic surfactant. Pharmaceutical formulations containing polysorbate 80 have been linked to hypersensitivity reactions, including anaphylaxis and irritation of blood vessels resulting in infusion-site pain. FDA-approved dosing administration included in the United States prescribing information for CINVANTI is a 30-minute infusion.

Please see Full Prescribing Information at www.CINVANTI.com.

About SUSTOL (granisetron) extended-release injection

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes Heron’s Biochronomer polymer-based drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy).

Please see Full Prescribing Information at www.SUSTOL.com.

About Chemotherapy-Induced Nausea and Vomiting (CINV)

While chemotherapy is one of the most effective and commonly used therapies to help patients fight cancer, it is accompanied by debilitating side effects, including varying degrees of nausea and vomiting, often attributed as a leading cause of premature discontinuation of cancer treatment. The goal of antiemetic therapy is to prevent CINV in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy). The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) have categorized chemotherapy regimens based on the degree to which they cause nausea and vomiting: low emetogenic chemotherapy (LEC); moderately emetogenic chemotherapy (MEC); and highly emetogenic chemotherapy (HEC).

On January 8, 2018 Incyte Corporation (NASDAQ:INCY) and Syros Pharmaceuticals, Inc. (NASDAQ:SYRS) reported that the companies have entered into a target discovery, research collaboration and option agreement. Under the agreement, Syros will use its proprietary gene control platform to identify novel therapeutic targets with a focus in myeloproliferative neoplasms (MPNs), and Incyte will receive options to obtain exclusive worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets (Press release, Incyte, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325356 [SID1234522990]). Incyte will have exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those validated targets.

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"The discovery and development of novel therapeutic approaches to treat MPNs is an important area of focus at Incyte," said Reid Huber, Ph.D., Chief Scientific Officer of Incyte. "Through this collaboration, we believe that Syros’ gene control platform will allow us to advance our understanding of the underlying biology of MPNs and potentially uncover new molecular targets for drug discovery."

"Our gene control platform has broad applicability across diseases," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "By working with Incyte, a leader in the discovery, development and commercialization of therapies for MPNs, we aim to leverage the promise of our platform to benefit patients with diseases beyond our current areas of focus. Meanwhile, we can continue advancing our own pipeline to achieve our long-term goal of building a fully integrated company with therapies that make a profound difference for patients."

Terms of the Agreement

Under the terms of the agreement, Incyte will pay Syros $10 million upfront – including $2.5 million in cash and $7.5 million in prepaid research and development (R&D) – and purchase a total of $10 million in Syros common stock at $12.61 per share.

Should Incyte exercise all of its options under the agreement, Syros could receive up to $54 million from Incyte in target selection and option exercise fees. For products resulting from the collaboration against each of the up to seven selected and validated targets, Syros could receive up to $50 million in development and regulatory milestones, as well as up to $65 million in commercial milestones. Syros would also be eligible to receive low single-digit royalties on sales of products resulting from the collaboration.

The transaction is effective immediately.