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Cullinan Oncology to Develop Novel EBNA1 Inhibitor Discovered by The Wistar Institute

On January 30, 2019 Cullinan Oncology, LLC and The Wistar Institute reported an agreement to accelerate the development of VK-2019, a novel EBNA1 (Epstein-Barr Nuclear Antigen 1) inhibitor discovered by The Wistar Institute (Press release, Cullinan Oncology, JAN 30, 2019, View Source [SID1234532970]).

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VK-2019 will be developed by Cullinan Apollo, a company formed and managed by Cullinan Oncology, LLC. Under the terms of the agreement, The Wistar Institute has granted an exclusive worldwide license for the development and commercialization of the EBNA1 inhibitor to Cullinan Apollo. Wistar has received an up-front license fee and an equity interest in Cullinan Apollo, with the potential to receive additional downstream milestones and royalty payments as the asset progresses.

"We look forward to advancing this highly novel, first-in-class asset into the clinic over the coming weeks," said Leigh Zawel, CSO, Small Molecules at Cullinan Oncology, LLC. "The Wistar scientists have spent nearly a decade developing this molecule, and we appreciate their confidence in our ability to successfully develop this EBNA1 inhibitor."

EBV (Epstein-Barr Virus), a well-established driver of various cancers, is critically reliant on the viral DNA-binding factor EBNA1 for viral genome maintenance. This new compound potently inhibits EBNA1 function. In preclinical models of EBV-associated cancer, it eliminated EBV, resulting in tumor growth inhibition. Development of this compound was largely supported by an investment of over U.S. $10 million from Wellcome, a biomedical research charity based in the United Kingdom.

"We are excited to work with the Cullinan Apollo team to embark on the next phase of clinical development of our lead therapeutic candidate for EBV-associated cancers," said Paul M. Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor, professor and leader of the Gene Expression and Regulation Program, and director of the Center for Chemical Biology and Translational Medicine at The Wistar Institute. "This drug is exemplary of the results of the hard work of my lab – most notably Dr. Troy Messick – together with our committed collaborators at Fox Chase Chemical Diversity Center, Inc. and invaluable input from Wellcome and its advisors. We need exceptional partners to work with us to move our discoveries forward, and this is one example of that."

Gossamer Bio Announces Updates Regarding its Initial Public Offering

On January 30, 2019 Gossamer Bio, Inc., a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, reported that it has filed an amended registration statement on Form S-1 with the U.S. Securities and Exchange Commission (the "SEC") in connection with its proposed initial public offering of its common stock (Press release, Gossamer Bio, JAN 30, 2019, View Source [SID1234532968]). The amended registration statement restores the delaying amendment language contemplated by Rule 473(a) promulgated under the Securities Act of 1933, as amended (the "Securities Act"), such that the registration statement Gossamer Bio filed on January 23, 2019 will no longer become automatically effective pursuant to Section 8(a) of the Securities Act 20 calendar days after its filing date. With today’s filing, Gossamer Bio intends to request from the SEC acceleration of the effective date of the registration statement prior to the date that it would have otherwise become automatically effective.

Gossamer Bio previously announced that it had filed a registration statement on January 23, 2019 offering 14,375,000 shares of its common stock at an initial public offering price of $16.00 per share. The proposed offering terms have not changed. Gossamer Bio’s common stock has been approved for listing on the Nasdaq Global Select Market under the symbol "GOSS." Gossamer Bio expects to grant the underwriters a 30-day option to purchase up to an additional 2,156,250 shares of common stock in connection with the offering. All of the shares are being sold by Gossamer Bio.

BofA Merrill Lynch, SVB Leerink, Barclays and Evercore ISI are acting as joint book-running managers for the proposed offering.

A registration statement relating to these securities has been filed with the SEC, but has not yet become effective. These securities may not be sold, nor may offers to buy be accepted, prior to the time the registration statement becomes effective. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any offer or sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

The proposed offering will be made only by means of a prospectus. Copies of the preliminary prospectus relating to the proposed offering may be obtained, when available, from: BofA Merrill Lynch, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email at [email protected]; or from SVB Leerink, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, or by email at [email protected], or by telephone at (800) 808-7525, ext. 6132; or from Barclays, c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (888) 603-5847, or by email at [email protected]; or from Evercore ISI, Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, or by telephone at (888) 474-0200, or by email at [email protected].

Newly Published Pre-Clinical Data Show Intratumoral Injections of Messenger RNA Encoding Three Immune Modulators Stimulate Durable Anti-Cancer Responses in Treated and Distal Tumors

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]).

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.

Eureka Therapeutics Announces US FDA Clearance of IND Application for Phase 1/2 Trial of ET140202 Artemis T-Cell Therapy, for the Treatment of Liver Cancer

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]).

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).

Can-Fite’s Drugs’ Potential Ability to Treat Cytokine Release Syndrome in Cancer Immunotherapy Published in Scientific Journal

On January 30, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that Drug Design, Development and Therapy has published an article titled, "Targeting the A3 Adenosine Receptor to Treat Cytokine Release Syndrome in Cancer Immunotherapy (Press release, Can-Fite BioPharma, JAN 30, 2019, View Source [SID1234532965])." The article presents data from numerous studies that show adenosine’s role in inhibiting inflammatory cytokine production. Can-Fite’s Piclidenoson, a Phase III drug candidate, and Namodenson, a Phase II drug candidate, both target the A3 adenosine receptor (A3AR), which the Company believes may treat cytokine release syndrome (CRS) while also promoting an anti-cancer effect.

CRS is a potentially life threatening side effect of cancer immunotherapies including CAR-T. The market for CAR-T drugs is estimated to reach approximately $5.4 Billion in 2024 according to Evaluate Pharma.

"While CAR-T and other cancer immunotherapies are saving lives, as their use increases, there is growing concern about the drugs’ life threatening side effects including the high incidence of CRS. With the publication of this article in Drug Design, Development and Therapy, we are advancing the scientific community towards delivering immunotherapies that offer a high degree of efficacy with a greater degree of safety for the patient. Our platform technology, through Namodenoson, has already displayed its anti-cancer effects in humans, and therefore it is a candidate to not only protect patients from CRS, but to also boost the body’s fight against cancer," stated Dr. Pnina Fishman, Can-Fite’s CEO. "We look forward to implementing our development strategy for our drugs in the treatment of CRS."

Can Fite’s platform technology selectively targets A3AR, which plays a central role in mediating the mechanism of inflammation by reducing elevated levels of pro-inflammatory cytokines such as IL-6, IL-1β, NF-Kβ, TNF-α, and more.