On January 30, 2019 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing antibody-TCR (AbTCR) T-cell therapies, reported that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for ET140202 ARTEMIS T-cell therapy in AFP-positive patients with advanced hepatocellular carcinoma (HCC), the most common type of liver cancer (Press release, Eureka Therapeutics, JAN 30, 2019, View Source [SID1234532966]).

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The Company plans to initiate its Phase 1/2 US multicenter clinical trial in the first half of 2019. The Phase 1 dose escalation portion of the trial will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ET140202. A dose expansion phase is planned to follow the selection of a recommended Phase 2 dose.

As previously reported in September 2018, Eureka presented data from a first-in-human study of ET140202 in China. The findings from the First Affiliated Hospital of Xi’An Jiaotong University demonstrated a favorable safety profile of ET140202 T-cell therapy in six patients with no observed cytokine release syndrome (CRS) or drug-related neurotoxicity. In addition, one patient in the i.v. arm of the study had a complete response. Overall, tumor regression was observed in three out of six patients.

"This is an exciting time for Eureka as we prepare to initiate our US clinical trial in patients with hepatocellular carcinoma," said Cheng Liu, Ph.D., President and Chief Executive Officer of Eureka Therapeutics. "HCC is an area of significant unmet medical need and patient options are currently limited. We intend to advance ET140202 as rapidly as possible in the US and to build upon the experience from our promising proof-of-concept study in China."

ABOUT LIVER CANCER

A highly unmet medical need, liver cancer is the second most common cause of cancer-related deaths, with roughly 600,000 patient deaths every year worldwide. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer that occurs in approximately 31,500 newly diagnosed patients per year in the United States. General 5-year survival rate of liver and intrahepatic bile duct cancer in the United States is only 18%.

ABOUT ET140202

ET140202 utilizes Eureka’s proprietary ARTEMIS T-cell receptor platform engineered with a proprietary human TCR-mimic (TCRm) antibody to target an AFP-peptide/HLA-A2 complex on HCC cancer cells. Using its proprietary E-ALPHA antibody discovery platform, Eureka developed a TCRm antibody to selectively bind an AFP peptide displayed on the cell surface by the HLA-A2 major histocompatibility complex (MHC).

On January 30, 2019 Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported the publication of pre-clinical data that shows the therapeutic potential of mRNA-2752, an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators designed to activate the immune system to recognize and eradicate tumors that are resistant to checkpoint inhibitors (Press release, Moderna Therapeutics, JAN 30, 2019, View Source [SID1234532967]).

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The study, published in the scientific journal Science Translational Medicine, found that the local delivery of mRNA encoding the secreted cytokines IL23 and IL36γ and the membrane-bound T-cell co-stimulator OX40L, induced a broad immune response promoting tumor regression in both injected lesions and distant un-injected tumors in mice. When combined with checkpoint inhibitors, mRNA-2752 boosted complete response rates in immunosuppressive and in immunologically barren tumor models that are otherwise unresponsive to checkpoint inhibitors.

"These pre-clinical data are important because they show how we can utilize multiple mRNAs encoding for immune modulators in a single therapy to activate a robust, systemic immune response against cancer in immunosuppressive and in so-called ‘cold’ tumors that are resistant to checkpoint inhibitors," said Joshua Frederick, Ph.D., Moderna’s head of oncology research. "We were pleased to discover the cooperation of the components encoded by this mRNA mixture in engaging innate immune cells, innate-like lymphocytes and effector T cells, ultimately resulting in complete tumor regressions and protective immunity in our mouse models of cancer."

"Unlike conventional biologics, we believe mRNA therapies can uniquely alter the tumor microenvironment to make cancers more susceptible to checkpoint inhibitors via a paracrine effect by producing high, local therapeutic concentrations of membrane-bound and secreted immunomodulators, both of which are believed to play a critical role in the immune response against cancer," said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. "This important study highlights why we are excited to have started our Phase 1 clinical study for mRNA-2752, as we believe the combination of these immune signals has the potential to help patients for whom checkpoint inhibitors alone have been insufficient."

The study showed that in a MC38-R mouse cancer model that is considered immunosuppressive and found to be unresponsive to checkpoint inhibitor immunotherapy, a single dose of the Triplet administered intratumorally led to complete responses (defined as the absence of all detectable cancer). After multiple injections in the immunosuppressive tumor model, complete response rates increased to a majority of the treated animals. In addition, a single dose of the Triplet led to near-complete control of both injected tumors and distal untreated tumors. The addition of anti-PD-L1, anti-PD-1 or anti-CTLA-4 checkpoint inhibitors to a single dose of the Triplet improved complete response rates over either mRNA or antibody treatment alone.

Moderna has advanced mRNA-2752 into a Phase 1 study (ClinicalTrials.gov Identifier: NCT03739931) and has started dosing patients with advanced or metastatic solid tumor malignancies or lymphoma. The open label, multi-center study is evaluating the safety and tolerability of mRNA-2752 as a monotherapy or in combination with either AstraZeneca’s durvalumab (anti-PD-L1 antibody) or tremelimumab (anti-CTLA-4 antibody) and will assess anti-tumor activity, protein expression in tumors and pharmacokinetics and exploratory endpoints that include assessment of immunological response.

A link to the publication, Durable anti-cancer immunity from intratumoral administration of IL-23, IL-36γ and OX40L mRNAs (S. L. Hewitt, et. al.), can be found here.

On January 29, 2019 Horizon Pharma plc (Nasdaq: HZNP) reported that its fourth-quarter and full-year 2018 financial results will be released on Wednesday, Feb. 27, 2019 (Press release, Horizon Pharma, JAN 29, 2019, View Source [SID1234532932]). Following the announcement, Horizon’s management will host a live webcast at 8 a.m. Eastern Time to review the Company’s financial and operating results.

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The live webcast and replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes before the live webcast to ensure adequate time for any software download that may be needed to access the webcast.

On January 29, 2019 Array BioPharma Inc. (Nasdaq: ARRY) reported that it will report financial results for the second quarter of fiscal 2019 and hold a conference call to discuss those results on Tuesday, February 5, 2019 (Press release, Array BioPharma, JAN 29, 2019, View Source [SID1234532950]). Ron Squarer, Chief Executive Officer, will lead the call.

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Date:

Tuesday, February 5, 2019

Time:

9:00 a.m. Eastern Time

Toll-Free:

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Toll:

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Pass Code:

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Webcast, including Replay and Conference Call Slides:
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On January 29, 2019 Triphase Accelerator, together with its majority shareholder FACIT, reported a new strategic collaboration with Celgene for a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia (Press release, Celgene, JAN 29, 2019, View Source [SID1234536469]). Triphase is a drug development company advancing novel compounds through Phase 2 proof-of-concept, including the WDR5 program.

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Under the terms of the agreement, Celgene has the option to acquire TRPH-395 from Triphase Accelerator. Celgene will pay an upfront of US$40M and upon exercise of the option, Celgene will pay up to US$940M in contingent development, regulatory and sales milestones. Additional payments for sales-based royalties are also possible.

"As with our previously announced spin outs, the Drug Discovery team at Ontario Institute for Cancer Research (OICR), led by Dr. Rima Al Awar, has yet again produced a world-class asset for patients with cancer," remarked Dr. David O’Neill, President of FACIT. FACIT seed financed Propellon Therapeutics to commercialize the preclinical asset and ran a competitive global business development process to identify strategic partners. Multiple formal offers were received from the US, Europe and Japan, reflecting the high quality of science in the program.

Dr. O’Neill continued "The quality of the team and commitment by Triphase Accelerator to engage Ontario researchers and clinical sites in its high content studies, combined with its long-standing relationship with Celgene made this partnership the most compelling path to impact patients and the local economy." While additional payments to the program are largely contingent on clinical success, the significant financial commitment will enable re-investable returns by FACIT in the Ontario innovation economy.

The WDR5 protein is critical for the formation and activities of certain protein complexes that are associated with DNA and indirectly modify genes. These processes represent an exciting new therapeutic field, referred to as epigenetics. Blood cancers like leukemia can result when WDR5-associated protein complexes are not appropriately regulated in the body. Drug compounds that can disrupt these cancer-causing cellular activities represent a novel therapeutic approach, which may also improve clinical outcomes in patients with solid tumours.

"This transaction represents a significant milestone for Triphase Accelerator as it brings together our long-standing collaboration with Celgene and a first-in-class asset from Ontario" said Dr. Ilse Treurnicht, Executive Chairperson at Triphase Accelerator. "We are excited that this transaction is another step forward to realizing the vision of the founding partners – OICR, MaRS Innovation and MaRS – and will allow Triphase to apply its unique science based, rapid, and cost-effective approach to advancing this Ontario based program toward clinical proof of concept."

"Our investment in Propellon’s technology reflects our commitment to developing first-in-class epigenetic therapies for patients with hematological cancers," remarked Dr. Jorge DiMartino, Vice President of Translational Development at Celgene. "The teams at OICR Drug Discovery, FACIT and Triphase Accelerator have together created an optimal pathway for oncology innovation and help make Ontario a strong collaborator and destination for our investment."

"This is a great day for cancer research in Ontario. Congratulations to FACIT, OICR and Triphase Accelerator," said Todd Smith, Minister of Economic Development, Job Creation and Trade. "This discovery and investment will benefit Ontario cancer patients and support industry jobs in the province. Ontario is open for business, and we welcome more innovative cancer research and trials."

"This is an exciting development for cancer research and innovation in Ontario, and I congratulate FACIT, OICR and Triphase Accelerator on their important collaboration," said Christine Elliott, Deputy Premier and Minister of Health and Long-Term Care. "It’s partnerships like these that keep Ontario open for business and are invaluable as we work toward developing a long-term transformational health care strategy guided by innovation, integration and the better use of technology."