On April 18, 2018 Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, www.provectusbio.com), ("Provectus" or the "Company"), a clinical-stage biotechnology company developing PV-10 as the first small molecule oncolytic immunotherapy for solid tumor cancers, reported that the Japan Patent Office (JPO) had granted and the European Patent Office (EPO) had allowed the Company’s patent application for the combination of PV-10 with systemic immunomodulatory therapy (i.e., immune checkpoint inhibition) (Press release, Provectus Biopharmaceuticals, APR 18, 2018, View Source [SID1234525516]).Pfizer, Inc. is a co-assignee on the award and allowance.

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The JPO patent and EPO patent allowance are related to U.S. patent (USP) 9,839,688, "Combination of rose bengal and systemic immunomodulative therapies for enhanced treatment of cancer," which was awarded by the United States Patent and Trademark Office (USPTO) in December 2017. USP 9,839,688 is one of the continuations of the Company’s foundational cancer combination therapy patent, USP 9,107,887, which was awarded by the USPTO in August 2015.

Provectus’ patent portfolio provides global intellectual property protection into the 2030s for the synthesis and use of PV-10 and other halogenated xanthene-based therapeutics as monotherapies and part of combination therapies for cancer.

About PV-10

Provectus’ lead investigational cancer drug product, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. It elicits tumor immunity via activation of dendritic cells mediated by the release of damage-associated molecular pattern molecules. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

On April 18, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that preclinical data from its TTI-622 (SIRPa-IgG4 Fc) immune checkpoint inhibitor program were presented at the 109th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Trillium Therapeutics, APR 18, 2018, View Source [SID1234525500]).

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TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. It consists of the CD47-binding domain of human SIRPa linked to an IgG4 Fc region and is being developed primarily for combination therapy.

The data presented at AACR (Free AACR Whitepaper) demonstrate that TTI-622 induces the phagocytosis of a broad panel of tumor cells derived from patients with both hematological and solid tumors. As a monotherapy, TTI-622 treatment resulted in decreased tumor growth and improved survival in a B cell lymphoma xenograft model, and enhanced the efficacy of cetuximab (anti-EGFR) and daratumumab (anti-CD38) antibodies in solid and hematological xenograft models, respectively. Unlike CD47-blocking antibodies, TTI-622 bound minimally to human erythrocytes and did not induce hemagglutination in vitro.

"The preclinical data presented at AACR (Free AACR Whitepaper) reinforce our confidence in this target and provide a solid foundation for initiating a clinical program with TTI-622," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. This second SIRPaFc decoy receptor complements TTI-621, and allows us to evaluate the effects of CD47 blockade using different levels of Fc receptor engagement. Importantly, we believe the minimal binding of TTI-622 to human red blood cells distinguishes this agent from other IgG4-based CD47 targeted therapies."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation study, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b study, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen.

On April 18, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CB-839 in combination with cabozantinib for the treatment of patients with metastatic renal cell carcinoma who have received one or two prior lines of therapy, including at least one vascular endothelial growth factor tyrosine kinase inhibitor or the combination of nivolumab and ipilimumab (Press release, Calithera Biosciences, APR 18, 2018, View Source [SID1234535241]). CB-839 is a first-in-class, oral, selective, potent inhibitor of glutaminase being evaluated in the CANTATA trial. The trial is a randomized double-blind clinical study of cabozantinib in combination with CB-839 or placebo in 298 patients with clear cell renal cell carcinoma. The primary endpoint is progression free survival and the global study is open for enrollment.

"Despite a number of new therapies for the treatment of renal cell carcinoma, there remains a significant unmet need among advanced patients who have received prior treatment," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are pleased that CB-839 has been granted Fast Track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our glutaminase inhibitor as an important new therapy for patients with advanced or metastatic renal cell carcinoma who have failed prior systemic therapy."

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The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs and biologics, to treat serious or life threatening conditions, and to fill an unmet medical need. Specifically, Fast Track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support approval, and also provides the opportunity to submit sections of an NDA on a rolling basis as data become available. About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents.

On April 18, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, "Astellas" ) and Kite, a Gilead Company (Nasdaq: GILD, President and CEO: John Milligan, "Kite"), reported that an agreement has been completed for the transfer of certain Agensys research facilities in Santa Monica, California, USA, to Kite (Press release, Astellas Pharma US, APR 18, 2018, View Source [SID1234525501]). The asset transfer was completed on April 12, 2018. Additional financial information or further deal terms are not being disclosed.

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Astellas is a pharmaceutical company dedicated to improving the health of people around the world. (PRNewsFoto/Astellas Pharma Inc.)

The facilities transfer is part of the wind-down process of the Agensys research operations, as announced by Astellas on July 27, 2017. Additional wind-down activities were completed in the first quarter of calendar year 2018, following the Company’s decision to further refine its oncology strategy by expanding its investment in the research of new technologies and modalities and reducing its focus on Antibody-Drug Conjugate (ADC) research, which was the core focus of work conducted at Agensys. Astellas will continue certain clinical trials and collaborations on some ADC programs that have been in progress at Agensys, including its collaboration with Seattle Genetics, Inc.

On April 18, 2018 Sosei Group Corporation ("Sosei" or the "Company"; TSE Mothers Index: 4565), the world leader in GPCR medicine design and development, reported that new preclinical data for AZD4635 was presented by AstraZeneca in a poster (abstract 3751) yesterday at the American Association of Cancer Research Annual Meeting, 17 April 2018; Chicago, IL, USA (Press release, Sosei, APR 18, 2018, View Source;sid=1573490 [SID1234525518]).

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AZD4635 is a potent and selective, orally available, small molecule adenosine A2A receptor (A2AR) antagonist. It was discovered by Sosei’s wholly-owned subsidiary Heptares Therapeutics and AstraZeneca licensed exclusive global rights to the molecule in 2015.

The poster is entitled "Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models," and highlighted the following results:

Adenosine signalling through the A2AR results in a range of immunosuppressive effects which can promote tumour growth
AZD4635 is an oral, specific A2AR antagonist that is demonstrated to reverse adenosine mediated T cell suppression.
Treatment with AZD4635 alone and in combination with an anti-PD-L1 antibody led to a significant reduction in tumour growth in syngeneic tumour models exhibiting both high and low levels of adenosine
These effects were absent in immune-deficient animals confirming the immune-mediated mechanism of action. Further exploration of target engagement by AZD4635 is ongoing.
These data suggest that AZD4635 has the potential to restore immune responsiveness resulting in anti-tumour benefits alone and in combination with other cancer immunotherapies irrespective of the background tumour adenosine levels
AZD4635 is currently in a Phase 1 clinical trial as a single agent and in combination with AstraZeneca’s anti-PD-L1 antibody IMFINZI (durvalumab) in patients with solid malignancies (NCT02740985).

Notes to Editors

About AZD4635

AZD4635 is a potent and selective, orally available, small molecule adenosine A2A receptor (A2AR) antagonist discovered by Sosei subsidiary Heptares Therapeutics and licensed to AstraZeneca in 2015. High levels of adenosine are found in tumour microenvironments and benefit the progression of cancer. By activating the adenosine A2A receptor increased adenosine levels impair T-cell function and result in suppression of the host immune response. AZD4635 specifically blocks adenosine signalling via the A2A receptor signalling resulting in increased immune responsiveness and potential to destroy cancer cells and decrease tumour burden, A2A receptor antagonism can therefore promote the anti-cancer response of T-cells within the tumour microenvironment, offering a novel mechanism of action as a mono- or combination therapy.