University of Pennsylvania Scientists Receive ACGT Grant to Accelerate CAR T-Cell Clinical Trial for Prostate Cancer

On January 31, 2020 A scientific team is developing a new CAR T-cell gene therapy treatment for advanced metastatic prostate cancer at the Abramson Cancer Center of the University of Pennsylvania (Philadelphia, Pennsylvania) with a $500,000 grant from Alliance for Cancer Gene Therapy (ACGT) (Press release, University of Pennsylvania, JAN 31, 2020, View Source [SID1234554029]).

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The ACGT grant was awarded to Joseph Fraietta, PhD, assistant professor of microbiology and a T-cell biologist with expertise in tumor immunology and translational medicine, and Naomi Haas, MD, director of the Prostate and Kidney Cancer Program, associate professor of medicine, and nationally renowned expert in the field of prostate and kidney cancer. The goal of the ACGT-funded study is to overcome prostate cancer’s stubborn resistance to CAR T-cell therapy, a therapy that has been successful in treating blood cancers. Drs. Fraietta and Haas are exploring approaches for re-engineering T-cells to enable them to induce safe, long-term remission for advanced, metastatic prostate cancer patients.

"The grant from ACGT will help us advance our clinical work in a very novel way," said Dr. Fraietta. "If we can unlock the epigenetic code that controls the fate and function of T-cells, it could be a game changer."

"The ACGT Scientific Advisory Council is impressed with the potential of this research team and their successful innovations in the use of T-cell therapy," noted Kevin Honeycutt, CEO and president of ACGT. "Because Drs. Fraietta and Haas are building on direct results already achieved with patients, there may be less transition time required to get a promising new treatment into the clinic for prostate cancer patients. Plus, we believe this research could provide a tumor-attack roadmap to help fight other cancers, including lung, pancreatic, ovarian and brain."

In the ACGT-funded study, Drs. Fraietta and Haas are going from the bedside back to the benchtop to employ new insight into how to better enable T-cells to battle cancer cells in solid tumors. Drs. Haas and Fraietta will explore the connection between nutrient availability and epigenetic programming, and how these factors influence the viability of T-cells and their anti-tumor functionality. This research builds on durable results being achieved by Dr. Haas in related prostate cancer clinical trials. In these trials, different doses of CAR T-cell gene therapies are being used to treat metastatic patients for whom traditional hormonal therapies, chemotherapies, radiation and surgery have failed.

"For so many years, chemotherapy, radiation and surgery were the traditional treatments for cancer. For prostate cancer, there’s also hormone therapy," said Honeycutt. "Unfortunately, as the cancer progresses, it often stops responding to these traditional treatments. New cell and gene therapy approaches like the ones Drs. Fraietta and Haas are employing offer new hope to all cancer patients. ACGT has been dedicated to funding innovative science that harnesses the power of cell and gene therapy and transforms how cancer is treated. The work of Drs. Fraietta and Haas is a great example of this promise."

ACGT has been instrumental in funding some of the decade’s most transformative research, including breakthroughs in the use of CAR T-cell gene therapy for leukemia by the University of Pennsylvania’s Carl H. June, MD. "Dr. June received his first ACGT grant in 2004 and a second in 2008, back when gene therapy was considered a risky proposition," says Honeycutt. "Fast forward to today and the field has changed dramatically with major pharmaceutical companies and research institutions vying for the next big discovery using gene therapy or immunotherapy."

To learn more about Alliance for Cancer Gene Therapy (ACGT), visit acgtfoundation.org, call 203-358-5055, or join the ACGT community on Facebook, Twitter, Instagram and YouTube. To learn more about University of Pennsylvania’s Abramson Cancer Center, visit pennmedicine.org/cancer.

Entry into a Material Definitive Agreement

On January 31, 2020, Sierra Oncology, Inc. (the "Company") reported that it has entered into a security purchase agreement (the "SPA") with Gilead Sciences, Inc. ("Gilead"), pursuant to which the Company agreed to (i) issue to Gilead 725,283 shares (the "Shares") of the Company’s common stock (the "Common Stock") and (ii) issue a warrant (the "Warrant") to purchase up to 725,283 shares of Common Stock (the "Warrant Shares"), with an exercise price equal to $13.20 per share, in consideration of the Company’s and Gilead’s agreement to amend that certain Asset Purchase Agreement dated August 20, 2018, as set forth in the Amendment to the Asset Purchase Agreement dated October 28, 2019 (Filing, 8-K, Sierra Oncology, JAN 31, 2020, View Source [SID1234553919]).

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The Warrant contains customary provisions allowing for adjustment to the exercise price and number of Warrant Shares issuable including in the event of any stock split, reverse stock split, stock dividend, other dividend or distribution of assets, recapitalization or similar transaction as described in the Warrant. In addition, subject to limited exceptions, Gilead will not have the right to exercise its Warrant to the extent that, after giving effect to such exercise, it, together with any affiliates, would beneficially own in excess of 9.99% of the number of shares of the Common Stock outstanding immediately after giving effect to such exercise, which percentage may be increased or decreased, from time to time, at Gilead’s election upon 61 days’ notice to the Company. The Warrant is exercisable from any time after the date of issuance, which was January 31, 2020, until its expiration on January 31, 2025.

The Shares, the Warrant, and Warrant Shares have not been registered under the Securities Act of 1933, as amended (the "1933 Act") and were issued in a private placement pursuant to Section 4(a)(2) of the 1933 Act.

Pursuant to the SPA, upon the request of Gilead, the Company will register the resale of the Shares and Warrant Shares.

As previously stated in a Current Report on Form 8-K filed with the Securities and Exchange Commission on November 13, 2019, a copy of the Amendment to the Asset Purchase Agreement will be filed with the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019.

The foregoing summaries of the SPA and the Warrant do not purport to be complete and are subject to and qualified in their entirety by the terms of the SPA and the Warrant, copies of which are attached hereto as Exhibit 10.1 and Exhibit 10.2, respectively, and are incorporated by reference herein.

Kezar Announces Pricing of $49.4 Million Public Offering of Common Stock and Pre-Funded Warrants

On January 31, 2020 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing novel small molecule therapeutics to treat unmet needs in autoimmune disease and cancer, reported the pricing of an underwritten public offering of 16,115,385 shares of its common stock, and to certain investors in lieu thereof, pre-funded warrants to purchase 2,884,615 shares of its common stock at an exercise price of $0.001 per share (Press release, Kezar Life Sciences, JAN 31, 2020, View Source [SID1234553781]). The public offering price of each share of common stock is $2.60 and the public offering price of each pre-funded warrant is $2.599. In addition, Kezar has granted the underwriters a 30-day option to purchase additional shares of common stock of up to 15% of the aggregate number of shares of common stock plus the shares of common stock underlying the pre-funded warrants being offered in the offering. The offering is expected to close on February 4, 2020, subject to customary closing conditions.

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Cowen, Wells Fargo Securities and William Blair are acting as joint book-running managers for the offering.

Kezar expects to receive gross proceeds of $49.4 million from the offering, before deducting underwriting discounts and offering expenses. Kezar intends to use the net proceeds from the offering primarily to fund the research and development of its product candidates, acquire or license products or technologies that are complementary to its own, although Kezar has no current plans, commitments or agreements with respect to any acquisitions or licenses as of the date hereof, and for working capital and general corporate purposes.

The securities described above are being offered by Kezar pursuant to an effective shelf registration statement on Form S-3 filed with the Securities and Exchange Commission ("SEC") dated July 3, 2019. A preliminary prospectus supplement relating to the offering is, and a final prospectus supplement related to the offering will be, filed with the SEC and available on the SEC’s website at View Source Copies of the preliminary and final prospectus supplements relating to the offering may be obtained, when available, by contacting Cowen and Company, LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926; Wells Fargo Securities, LLC Attention: Equity Syndicate Department, 500 West 33rd Street, New York, New York 10001, by telephone at (800) 326-5897 or by email at [email protected]; or William Blair & Company, L.L.C. Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, Illinois 60606, by telephone at (800) 621-0687 or by email at [email protected]

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

NAVROGEN OPENS R&D OPERATIONS AT CHEYNEY UNIVERSITY

On January 31, 2020 Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, reported the opening of its R&D operations at the Cheyney University science center located in Chester County, PA (Press release, Navrogen, JAN 31, 2020, View Source [SID1234553754]). The move enables the company to expand its proprietary Humoral Immuno Oncology (HIO) technology discovery efforts to identify HIO-suppressed cancer types and development of therapeutic agents that can unlock a patient’s immune system to combat their cancer.

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A subset of tumors produce immune checkpoint factors that suppress a patient’s immune response to attack and destroy dysregulated cancer cells. HIO-suppressed cancers produce proteins, called HIO-factors, that suppress antibody-mediated "humoral" immune responses that are generated by a patient’s immune system to attack dysregulated cancer cells. These factors can suppress antibody-mediated tumor cell killing of those generated by a patient’s humoral immune response as well as antibody-based drugs including Rituxan in non-Hodgkin’s Lymphoma and Herceptin in metastatic breast cancer. Navrogen’s mission focuses on therapeutic solutions to reverse HIO suppression through proprietary screening platforms to identify tumor produced HIO-factors as well as develop therapeutic agents that can overcome a HIO-factor’s immuno-suppressive effect.

"The move to Cheyney enables us to transition to the next phase of our strategic growth plan as we continue to advance the development of our technology platforms and experimental therapies to identify and combat HIO-suppressed cancer types," stated Nicholas Nicolaides, Ph.D., Chief Executive Officer at Navrogen. "As part of the relationship with Cheyney, we will teach students the concepts of cancer immunity and provide them first-hand training in biomedical research to support the University’s mission of bringing unique experiential learning to their students as the company leverages the use of Cheyney’s state-of-the-art research facility and operational maintenance."

Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T cell-mediated anti-tumor responses

On January 31, 2020 Oncotarget reported Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade (Press release, Oncotarget, JAN 31, 2020, View Source [SID1234553748]).

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Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.

Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608,USA said, "It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimizes the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer."

The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.

These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors.

Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.

The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.

Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:

increased interferon production,
induction of immunogenic cell death,
increases in effector T cells, and
increases in functional NK cells,
…likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.

The Janatpour research Team concluded that, taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.