On January 12, 2017 Kitov Pharmaceuticals Holdings Ltd. (NASDAQ: KTOV; TASE: KTOV), an innovative biopharmaceutical company, reported the expansion of its pipeline through the acquisition of a majority stake in TyrNovo Ltd., a privately held developer of novel small molecules in the immuno-oncology therapeutic field (Press release, Kitov Pharmaceuticals , JAN 12, 2017, View Source [SID1234517379]).

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The expansion into developing immuno-oncology drugs comes as Kitov plans to file its New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for its flagship combination drug, KIT-302, which is intended to treat osteoarthritis pain and hypertension simultaneously, in Q1 2017, with commercial launch anticipated for the first half of 2018. Kitov plans to harness its development and regulatory capabilities in proceeding towards submitting an investigational new drug (IND) application with the U.S. FDA and initiate clinical trials for its newly acquired drug, NT219.

The market for immuno-oncology treatments is believed to become worth $14 billion by 2019 and to grow to $34 billion by 2024, driven by long-term and durable tumor responses to immuno-oncology drugs, according to Global Data.

Kitov will initially acquire an approximately 56% equity stake in TyrNovo from its majority shareholder, for consideration of $2 million in cash and $1.8 million equivalent ordinary shares of Kitov based on the closing price of Kitov’s shares on the TASE on January 11, 2017. Following the closing of this initial acquisition, which is expected to take place on January 13, 2017, Kitov anticipates that it may acquire additional equity stakes in TyrNovo from all or part of TyrNovo’s additional minority shareholders for consideration consisting of ordinary shares of Kitov in such amounts as to be agreed with the shareholders.

"The TyrNovo acquisition represents a major milestone in Kitov’s strategic vision of establishing a diverse pipeline that we believe will secure long term value creation for its shareholders. We are excited about NT219 and its prospects in the oncology field. NT219 can be developed as a platform combination drug for overcoming multi-drug resistance often observed in various tumors. It has the potential to be developed as a combination therapy with several approved oncology drugs for multiple types of tumors," stated Dr. Paul Waymack, Kitov’s Chairman and Chief Medical Officer.

"The Kitov regulatory team has a proven track record in the development and approval of drugs for oncology as well as other indications required to develop NT219 towards submission of an IND and initiation of clinical trials," Waymack added.

TyrNovo is led by its CEO, Dr. Hadas Reuveni, a co-inventor of the TyrNovo technology, who received her Ph.D., Summa Cum Laude, for anti-cancer drug discovery from the Hebrew University of Jerusalem and has nearly two decades of R&D experience in Biotechnology. Dr. Reuveni commented, "I am excited to join Kitov and its team to expedite the development of NT219, which addresses a true unmet medical need for numerous oncology indications. Cancer drug resistance is the major reason for failure in anti-cancer drug treatment. Preventing resistance to the drugs is critical for improving effective cancer treatment."

About NT219

NT219 is a small molecule that presents a new concept in cancer therapy by promoting the degradation of two oncology-related checkpoints, Insulin Receptor Substrates (IRS) 1 and 2 as well as the inhibition of signal transducer and activator of transcription 3 (STAT3). While targeted anti-cancer drugs inhibit the "ON" signal, NT219 activates the "OFF" switch, extensively blocking major oncogenic pathways. In pre-clinical trials, NT219, in combination with several approved cancer drugs, displayed potent anti-tumor effects and increased survival in various cancers by preventing the tumors from developing multi-drug resistance and ameliorating multi-drug resistance after resistance is acquired. NT219, in combination with various approved oncology drugs, demonstrated potent anti-tumor effects and increased survival in various cancer models including sarcoma, melanoma, pancreatic, lung, ovarian, head & neck, prostate and colon cancers, through the prevention of acquired resistance and regression of resistant tumors.

On January 12, 2017 Heron Therapeutics, Inc. (NASDAQ:HRTX), a commercial-stage biotechnology company focused on developing novel best-in-class treatment solutions to address some of the biggest unmet patient needs, reported submission of the New Drug Application (NDA) for CINVANTI (HTX-019), the first polysorbate 80-free, intravenous formulation of aprepitant for the prevention of CINV, to the U.S. Food and Drug Administration (FDA) (Press release, Heron Therapeutics, JAN 12, 2017, View Source;p=RssLanding&cat=news&id=2237084 [SID1234517367]). Aprepitant belongs to a class of agents known as NK1 receptor antagonists, which are often used in combination with 5-HT3 receptor antagonists for the prevention of CINV.

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The NDA filing includes data demonstrating the bioequivalence of CINVANTI to EMEND IV (fosaprepitant), supporting its efficacy for the prevention of both acute and delayed CINV with both moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC). Results also showed CINVANTI was better tolerated than EMEND IV, with significantly fewer adverse events reported with CINVANTI.

"The filing of the NDA for CINVANTI is an important milestone, bringing us one step closer to a new NK1 receptor antagonist treatment option for cancer patients suffering from the debilitating side effects of chemotherapy," said Kimberly J. Manhard, Executive Vice President, Drug Development at Heron Therapeutics. "We look forward to working closely with the FDA during the review of the NDA for CINVANTI in anticipation of FDA approval in late 2017."

"CINVANTI is based on the most widely used NK1 receptor antagonist, with almost 9 years of safety and efficacy experience," said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron Therapeutics. "Since NK1 receptor antagonists are used in combination with 5-HT3 receptor antagonists, CINVANTI offers a strong strategic and operational fit with Heron’s existing commercial product, SUSTOL, our extended-release, injectable product that incorporates the 5-HT3 receptor antagonist granisetron and is also indicated for the prevention of CINV."

About CINVANTI (HTX-019) for CINV
CINVANTI is a proprietary intravenous formulation of aprepitant, a NK1 receptor antagonist for the prevention of CINV. NK1 receptor antagonists are typically used in combination with 5-HT3 receptor antagonists. Currently, the only injectable NK1 receptor antagonist approved in the U.S. contains polysorbate 80, a surfactant, which may cause hypersensitivity reactions, infusion site reactions or other adverse reactions in some patients. Heron’s formulation for CINVANTI does not contain polysorbate 80 and may have a lower incidence of certain types of adverse reactions than reported with the other commercially available injectable NK1 receptor antagonist.

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 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 trials that evaluated efficacy and safety in more than 2,000 patients with cancer. The efficacy of SUSTOL in preventing nausea and vomiting was evaluated in both the acute phase (day 1 following chemotherapy) and the delayed phase (days 2-5 following chemotherapy). Please see full prescribing information, including additional important safety information, available at www.SUSTOL.com.

On January 12, 2017 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology Company focused on the treatment of primary and metastatic liver cancers, reported that patient treatment and data collection for the intrahepatic cholangiocarcinoma (ICC) cohort of its European Phase 2 HCC/ICC study is ongoing, and that the Company will announce interim results for the cohort once the data are fully mature (Press release, Delcath Systems, JAN 12, 2017, View Source;p=RssLanding&cat=news&id=2237085 [SID1234517366]). Additionally, the Company believes that the original goal to obtain an efficacy signal for the Phase 2 ICC cohort has been satisfied by the result of multicenter patient outcomes identified in the retrospective data collection of our commercial ICC cases conducted by our European investigators. These promising outcomes and observations were discussed with Key Opinion Leaders (KOL) at a Delcath-organized medical advisory panel meeting and led to the agreement that PHP therapy does, indeed, "demonstrate an efficacy signal in ICC and is worthy of full clinical investigation."

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The Company also announces that it has accepted an invitation from The Cholangiocarcinoma Foundation (CCF) to present its initial research plans for use of PHP therapy in the treatment ICC. The CCF is the largest patient advocacy organization devoted to finding a cure and improving the quality of life for patients with cholangiocarcinoma, or bile duct cancers. Company representatives will present a summary of European investigator findings and its clinical development plans for ICC to the Foundation’s medical advisory board at the CCF’s 2017 Annual Meeting, to be held in Salt Lake City, UT from February 1-3, 2017. Delcath will also provide a sponsorship grant to support the work of the CCF as part of its participation in the CCF Annual Meeting.

"Though the interim data we expected for ICC cohort in our Phase 2 trial in HCC/ICC are not yet available, the objectives for this study have largely been satisfied by the independent retrospective analysis conducted by our European investigators" said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "The promising outcomes and observations identified at our global KOL forum last year provide us with considerable confidence in the potential of our therapy in the ICC tumor type and helped form our initial research plan. The future research in ICC is designed to be cost effective and pursued in a financially prudent manner."

Dr. Simpson continued, "the CCF is one of the most important organizations for patients diagnosed with bile duct cancers, and the organization has attracted the participation of some of the leading researchers working on this difficult to treat disease. We are delighted with the opportunity to present to KOLs in this space the potential that the European investigators have identified for our therapy in the treatment of ICC."

About ICC
ICC is the second most common primary liver tumor and represents approximately 15% of new hepatocellular carcinoma (primary liver cancer or HCC) cases diagnosed annually. Surgical resection, the standard of care, is not possible for an estimated 80% to 90% of patients diagnosed with ICC.

On January 11, 2017 CureVac, a clinical-stage biopharmaceutical company pioneering the field of mRNA-based technology, reported an update of its clinical progress at the 35th Annual J.P. Morgan Healthcare Conference in San Francisco(Press release, CureVac, JAN 11, 2017, View Source [SID1234518820]).

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Interim Results of Phase I First-in-Human Clinical Trial with CV7201, an RNActive Rabies Vaccine
CureVac’s first-in-human phase I clinical trial with an mRNA-based rabies vaccine was designed to evaluate CV7201 in healthy volunteers without pre-existing immunity against the rabies virus. CV7201 encodes for the G protein of the rabies virus. To date, the vaccine appears well tolerated and no safety concerns were identified. In one cohort of 21 subjects vaccinated at the lowest dose of 80 µg with a needle-free device, virus neutralizing antibodies (VNTs) were detected in all subjects and in 17 (81%) exceeded the threshold considered protective by the WHO (0,5 IU/ml). The complete data set will be published after completion of a long-term safety valuation.
Regarding CV7201, CureVac is developing an optimized vaccine, which shows good efficacy when injected intramuscularly with a conventional needle. The company is planning to bring this vaccine into clinical testing in 2017.

Topline Result of Phase IIb Clinical Trial with CV9104, an RNActive Prostate Cancer Vaccine
CureVac’s double-blinded and placebo controlled phase IIb clinical trial with CV9104 was designed to evaluate the investigational mRNA-based cancer vaccine in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. CV9104 is composed of six protamine-formulated mRNAs, encoding individually for self-antigens that are overexpressed in prostate cancer patients.
CV9104 failed to meet the primary endpoint of improving overall survival. Progression-free survival was similar in both arms of the clinical trial. No safety concerns were identified confirming the favorable safety results of previous trials with RNActive cancer vaccines. CureVac is continuing to evaluate the data and plans to present the full set of data at an upcoming medical conference.

Clinical Results to Point Way Forward to Medical Innovation
Ingmar Hoerr, Ph.D., co-founder and CEO of CureVac, stated: "We received encouraging data from the first ever clinical trial of a prophylactic RNActive mRNA vaccine in immune-naïve healthy volunteers indicating our vaccine is able to effectively prime immune responses against a viral antigen. These results affirm the prior preclinical proof of concept data for our vaccine format and pave the way for us to advance more potent prophylactic vaccine formulations into the clinic. Regarding our CV9104 program, we now recognize that this therapeutic vaccine fails to induce a survival benefit as a monotherapy in patients with metastatic prostate cancer receiving standard of care therapies. However, we see the path forward for our RNActive cancer immunotherapy in combination with checkpoint inhibitors."
Dr. Hoerr continued, "Having administered our RNA technologies to more than 450 human subjects and having conducted eight different clinical studies, we are confident that it can be administered safely, and based on data generated in our clinical program in rabies, we now have clear evidence that our RNActive technology induces effective immune responses in humans. As the pioneer in the mRNA field, we look forward to advancing our mRNA development and applying uniquely designed mRNA-based drugs in oncology, prophylactic vaccines and molecular therapies as CureVac strives to have the first mRNA-based product on the market for people suffering from high and unmet medical needs."

About CV7201 Phase I Clinical Trial in Rabies
The study is designed to evaluate the safety and immunogenicity of CV7201 according to (1) dose level (2) route of injection and (3) injection schedule. Rabies-specific binding and neutralizing titers will be evaluated across different injection routes using an injection schedule of 0-7-28 and 0-28-56. The trial started in 2013 and is still ongoing. To date, more than 100 subjects have been enrolled in Germany and safety follow-up is ongoing.

More details can be found here.

About CV9104 Phase IIb Clinical Trial in Prostate Cancer
The phase IIb with CV9104 was a double-blind, placebo controlled trial with 197 chemo-naïve, asymptomatic or minimally symptomatic patients with metastatic, castrate-resistant prostate cancer randomized to CV9104 or placebo. The trial which was conducted in eight European countries started in 2012 and recruitment was completed in December 2013. The primary endpoint of the study was overall survival and key secondary endpoints were progression-free survival and change of quality of life.