On July 18, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported it has received the approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with a Phase 1/2a clinical trial of TG6002 administered by intrahepatic artery (IHA) infusion in colorectal cancer patients with unresectable liver metastases (CRLM) (Press release, Transgene, JUL 18, 2019, View Source [SID1234537599]).

TG6002 is a next-generation oncolytic virus (OV), which has multiple mechanisms of action. It has been engineered to combine the killing of cancer cells (oncolysis), the production of 5-FU, a widely used chemotherapeutic agent, in the tumor site, and the eliciting of an immune response against tumor cells. TG6002 expresses the proprietary FCU1 gene in the cancer cells it has infected, leading to local conversion of the pro-drug 5-FC (administered orally) into 5-FU. This is particularly important as most gastrointestinal tumors are 5-FU sensitive. TG6002 has been shown to induce both response in the primary tumor and an immune-mediated regression of distant metastases in preclinical experiments1.

"Current systemic therapies prolong survival of CRLM patients at the cost of significant side effects. We believe that TG6002 therapy administered via an IHA infusion potentially offers an additional effective and well tolerated treatment modality for these difficult to treat patients. By administering it via the intrahepatic artery, we believe we can conveniently deliver more concentrated doses of TG6002 to the tumor, to achieve better outcomes for unresectable colorectal cancer, whilst limiting systemic exposure. In parallel, Transgene is conducting a Phase 1/2 trial to investigate TG6002 in colorectal cancer patients when given intravenously," said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

Dr. Adel Samson, MB ChB PhD, Medical Oncologist at St. James’ University Hospital, is the Chief Investigator of the trial.
This trial is a single-arm open-label Phase 1/2a trial evaluating the safety, pharmacokinetics and efficacy of repeated and ascending doses of TG6002 administered by IHA route in combination with oral 5-FC, a non-cytotoxic pro-drug that can be converted in 5-FU. The study is expected to start in Q4 2019 and could enroll up to 75 patients.

— End–

About TG6002
TG6002 is a next generation oncolytic immunotherapy. It has been designed to induce the breakdown of cancer cells (oncolysis) and allow the local production of chemotherapy (5-FU) in the tumor. TG6002 is a modified Vaccinia virus, with double gene deletion (TK-RR-), and expressing the proprietary FCU1 gene in the cancer cells it has infected, leading to the local conversion of the non-cytotoxic pro-drug, flucytosine (5-FC), into 5-FU, a widely used cancer chemotherapy. The oncolytic virus TG6002 has shown efficacy and good safety profile in several preclinical models. Transgene believes that TG6002 may represent a new therapeutic option in recurrent cancer patients.
Another Phase 1/2 trial using TG6002 administered intravenously is ongoing in Europe in patients with advanced gastrointestinal tumors.

About Colorectal cancer
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide. In 2012, there were 447,000 new cases of CRC in Europe with 215,000 deaths and worldwide, there were 1.4 million new cases with 694,000 deaths (Ferlay J. et al., 2013, Ferlay J. et al., 2015). Approximately half of all CRC patients develop liver metastases, only a small proportion of whom being suitable for potentially curative hepatic resection (Leporrier J, 2006). Over the last decade, the clinical outcome for patients with metastatic CRC (mCRC) has improved. Today, the median overall survival (OS) for patients with mCRC is ∼30 months.

On July 18, 2019 Kronos Bio, Inc. (Kronos), a Two River portfolio company, reported it has closed a $105 million Series A Preferred Stock financing (Press release, Kronos Bio, JUL 18, 2019, View Source [SID1234537600]). The financing was led by Vida Ventures, LLC and Omega Funds and included participation from Nextech, GV (formerly Google Ventures), Perceptive Advisors, Invus and Polaris Partners. This Series A round also included significant participation from Kronos’ President and Chief Executive Officer, Norbert Bischofberger, Ph.D. as well as members of the Board of Directors including Arie Belldegrun, M.D., FACS and John Martin, Ph.D. In conjunction with this financing, Jakob Loven, Ph.D., Partner at Nextech, will join the Board of Directors of Kronos Bio.

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Kronos’ Small Molecule Microarray platform (SMM) was built on more than a decade of research by its scientific founder, Angela Koehler, Ph.D., Associate Professor of Biological Engineering at the Massachusetts Institute of Technology. SMM is ideally suited for the rapid discovery of novel modulators or degraders of historically undruggable targets, such as transcription factors. Kronos has demonstrated SMM’s potential to identify compounds that bind to target proteins directly or interfere at nanomolar potency with protein activity. SMM enables discovery of hits that act through a variety of mechanisms, including disruption of protein-protein or protein-DNA interactions, or indirect modulation of target protein activity by binding to co-factors or other protein complex members.

"We are excited to have the continued support of high caliber investors who recognize the potential of Kronos’ technology and its team. This financing will help us advance two preclinical programs built upon hits identified from SMM screens, accelerate our research, and further expand the Kronos team in the Boston and San Francisco areas," said Norbert Bischofberger, Ph.D., President and Chief Executive Officer of Kronos. "We seek to challenge the historic belief that certain targets cannot be pursued. Our goal is to unlock new therapeutic approaches and bring treatments to areas with high unmet need."

Existing therapies target only a minority of the body’s proteins, which are well-structured and accessible to traditional small molecule approaches. The majority of proteins, however, are disordered or lack obvious binding pockets and have historically been considered undruggable. Kronos’ platform enables high-throughput screens of chemical libraries against such target proteins in a more physiologically relevant context to identify biologically active small molecules.

"When we founded Kronos at Two River, we identified early on the need for support by investors who embrace cutting edge innovation," said Joshua Kazam, a Kronos Board Member and a Director at Vida Ventures. "With this Series A round, we have expanded support with investors equally as passionate about funding scientific breakthroughs to impact how we treat some of the most challenging diseases we face today."

"Since our initial investment, we have been very excited about the opportunity to identify novel therapies provided by the Kronos platform: we believe this is a huge opportunity not just for investors but more importantly, for addressing unmet needs in hard-to-treat diseases," said Otello Stampacchia, Ph.D., a Kronos Board Member and Founder and Managing Director of Omega Funds. "We are delighted to co-lead this milestone Series A financing and to be a part of the Kronos Bio team in this journey."

On July 17, 2019 Intensity Therapeutics, Inc., a clinical-stage biotechnology company pioneering a novel, immune-based approach to treat solid tumor cancers through direct injection of the company’s proprietary therapeutic agents, reported the publication in the journal OncoImmunology of results from nonclinical research conducted in partnership with the National Cancer Institute’s (NCI) Vaccine Branch under a Cooperative Research and Development Agreement (CRADA) (Press release, Intensity Therapeutics, JUL 17, 2019, View Source [SID1234537570]). All results and data reported in the paper were generated at the NCI.
"The results of this study are noteworthy because they demonstrate the anti-cancer benefits of INT230-6 extend beyond direct killing of the injected tumor to fighting tumors throughout the body by immune activation," said Anja C. Bloom, Ph.D., first author and former visiting postdoctoral researcher at the NCI Vaccine Branch, who conducted the majority of the work at the NCI. "We believe this is the first time that the well-known agents comprising INT230-6, cisplatin and vinblastine showed induction of a durable immune activation. We believe this result is due to the intratumoral delivery mechanisms of the compound, which appears to cause cell death that also releases antigens to initiate an adaptive immune response."

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The peer-reviewed paper entitled "Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory," describes the immune response induced from direct injection of Intensity’s lead product candidate, INT230-6, into subcutaneously implanted murine colon and orthotopic breast tumors. Treatment resulted in regression from baseline in 100 percent of tumors and complete response in up to ninety percent of mice. Studies that knocked out the mouse immune cells prevented complete responses, indicating a critical role of immune cells in treatment benefit. Mice with complete responses were protected from subcutaneous and intravenous re-challenge of the cancer, revealing that long-term immunological memory was induced by INT230-6.

Complete remission of the primary tumors was accompanied by shrinking and disappearance of a number of untreated contralateral tumors when INT230-6 was combined with checkpoint inhibitors, demonstrating not only a local but also systemic immunological effect.

"Our work with Intensity Therapeutics was to evaluate the benefits of INT230-6 because of its delivery directly into solid tumors," said Jay A. Berzofsky, M.D., Ph.D., Chief of the Vaccine Branch at the National Cancer Institute. "The results show that not only was complete regression achieved in a majority of injected tumors, but T cell immunity and immunological memory to the cancer were induced, associated with regression observed also in non-injected tumors and synergy when INT230-6 was combined with anti-PD-1 and anti-CTLA-4 antibodies. The treatment converts the tumor to an endogenous vaccine. Our results suggest that intratumoral approaches can be designed to provide a new strategy for effective immunotherapy of cancer."

"Intensity Therapeutics entered into the CRADA with the NCI in 2014, and this peer-reviewed publication is the culmination of that research. The positive results described in the paper demonstrate the unique potential of our novel cancer treatment approach," said Lewis H. Bender, Founder, President and Chief Executive Officer of Intensity Therapeutics. "We are currently evaluating INT230-6 in a Phase 1/2 clinical trial and have tested the drug in 15 different types of solid tumor cancers with promising results. The research with the NCI helped us design our clinical trial, and we recently presented clinical data at ASCO (Free ASCO Whitepaper) that indicate local treatment with INT230-6 alone in certain tumor types regresses injected tumors and initiates a systemic immune activation with results similar to the effects reported in our OncoImmunology paper. The nonclinical and clinical data generated to date increase our optimism about the potential of INT230-6 to kill tumors locally, activate the immune system, reduce the side effects associated with current systemic therapies and improve patient outcomes with achievement of a long-term, durable response for a number of cancers."

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors and diffuse into cancer cells. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor kill and recruitment of dendritic cells to the tumor micro-environment that induced anti-cancer T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-inoculations of the initial cancer and resistance to other cancers. In mouse models, INT230-6 has shown strong synergy with checkpoint blockage, including anti-PD-1 and anti-CTLA4 antibodies. INT230-6 was discovered from Intensity’s DfuseRxSM platform.

On July 17, 2019 Xenetic Biosciences, Inc. (NASDAQ: XBIO) ("Xenetic" or the "Company"), a clinical-stage biopharmaceutical company focused on the discovery, research and development of next-generation biologic drugs and novel orphan oncology therapeutics, reported the pricing of an underwritten public offering of 2,300,000 shares of its common stock (or pre-funded warrants to purchase common stock in lieu thereof) and warrants to purchase up to 2,300,000 shares of the Company’s common stock (Press release, Xenetic Biosciences, JUL 17, 2019, View Source [SID1234537586]). Each share of common stock is being sold together with one warrant to purchase one share of common stock at a combined price to the public of $6.50 per share and warrant. Gross proceeds, before underwriting discounts and commissions and estimated offering expenses, are expected to be approximately $15.0 million.

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The warrants will be immediately exercisable at a price of $13.00 per share of common stock and will expire five years from the date of issuance. The warrants are expected to begin trading on the Nasdaq Capital Market on July 19, 2019 or as soon thereafter as practicable, under the symbol "XBIOW." The warrants also provide that if the weighted-average price of common stock on any trading day on or after 30 days after issuance is lower than the then-applicable exercise price per share, each warrant may be exercised, at the option of the holder, on a cashless basis for one share of common stock. The shares of common stock and the accompanying warrants, can only be purchased together in the offering, but will be issued separately and will be immediately separable upon issuance. The offering is expected to close on or about July 19, 2019, subject to customary closing conditions.

Maxim Group LLC is acting as sole book-running manager in connection with the offering.

Xenetic also has granted to the underwriter a 45-day option to purchase up to an additional 345,000 shares of common stock and/or warrants to purchase up to 345,000 shares of common stock, at the public offering price less discounts and commissions.

The offering is being conducted pursuant to the Company’s registration statement on Form S-1 (File No. 333-231508) previously filed with and subsequently declared effective by the Securities and Exchange Commission ("SEC"). A prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at View Source Electronic copies of the prospectus relating to this offering, when available, may be obtained from Maxim Group LLC, 405 Lexington Avenue, 2nd Floor, New York, NY 10174, at (212) 895-3745.

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.

On July 17, 2019 NuCana plc (NASDAQ: NCNA), a clinical-stage biopharmaceutical company focused on significantly improving treatment outcomes for patients with cancer, reported that the first patients have been dosed in the Phase I study of NUC-7738 (Press release, Nucana BioPharmaceuticals, JUL 17, 2019, View Source [SID1234537571]). This is the third ProTide NuCana has advanced to clinical studies and further broadens the therapeutic scope of the ProTide portfolio. NUC-7738 is NuCana’s ProTide transformation of 3’-deoxyadenosine (or cordycepin), a novel nucleoside analog with a unique mode of action, that has shown potent anti-cancer activity in preclinical studies.

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Hugh Griffith, NuCana’s Chief Executive Officer, stated: "The dosing of the first patients in this Phase I study of NUC-7738 is another major step in the expansion of NuCana’s product pipeline. NUC-7738 is our third ProTide to advance to the clinic and the first that is based on a novel nucleoside analog. We are grateful to the patients and clinicians who are making this study possible."

More information about this study may be found here.

NUC-7738 is a ProTide transformation of cordycepin, a nucleoside analog that was isolated from the fungus Cordyceps sinensis in 1950. Cordycepin has demonstrated potent anti-cancer activity in multiple preclinical studies, but has not been successfully developed primarily due to its degradation by the enzyme adenosine deaminase (or ADA). Unlike the parent nucleoside analogue, NUC-7738 is not a substrate for this enzyme and is therefore resistant to degradation by ADA. Similar to NuCana’s other ProTides, NUC-7738 is designed to generate significantly higher levels of the active anti-cancer metabolite of cordycepin, 3’-deoxyadenosine triphosphate (or 3’-dATP), directly inside cells, bypassing the resistance mechanisms of transport, activation and breakdown.

Sarah Blagden, Associate Professor of Experimental Cancer Therapeutics at The University of Oxford and Principal Investigator of the study stated: "Oxford Early Phase Trials unit has enrolled the global first cancer patient to receive NUC-7738, the latest ProTide anti-cancer agent from NuCana’s pipeline. This is an exciting study to participate in and we look forward to seeing the clinical results."