On February 11, 2019 Hemispherx Biopharma, Inc. (NYSE American: HEB), an immuno-pharma company focused on unmet medical needs in immunology and oncology, reported the start at the UPMC Hillman Cancer Center in Pittsburgh, PA of a new clinical study supported by Merck that will combine the company’s Ampligen with Merck’s Keytruda for the treatment of recurrent, platinum-sensitive, ovarian cancer (Press release, Hemispherx Biopharma, FEB 11, 2019, View Source [SID1234533230]). The study will enroll up to 45 participants and be conducted at UPMC, which is sponsoring the study, by Robert Edwards, MD, director of the Ovarian Cancer Program at UPMC Magee Womens Hospital. The overall funding and support for the clinical trial and the supply of Keytruda is based upon a collaboration between Merck and UPMC. Hemispherx is not funding the clinical trial and its collaboration obligation relates to supplying the Ampligen needed for the clinical trial. Over the past year, Hemispherx has produced 16,000 vials of Ampligen, including all of the supply of Ampligen needed for this clinical trial. Hemispherx shipped Ampligen for the clinical trial to UPMC on January 29, 2019 and the first subject was enrolled. The company believes the study will be an important and more extensive test of Ampligen as an immune system primer that can convert "cold" tumors into "hot" tumors, thereby making the formerly "cold" tumors more responsive to Keytruda. View Source;cond=Ovarian+Cancer&cntry=US&state=US%3APA&city=Pittsburgh&rank=1

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This clinical trial will study how well Ampligen-based combination therapy works when given with Cisplatin and Keytruda in treating participants with recurrent ovarian cancer compared to historical controls. Drugs used in this combination therapy work by either direct antitumor activity, or by unleashing or enhancing the cancer immune responses that already exist. So called "checkpoint inhibitors" such as Merck’s Keytruda interfere with the ability of tumor cells to grow and spread when present in a "hot" tumor microenvironment. The clinical trial tests whether the combination therapy will work better than Keytruda alone in treating participants with ovarian cancer. Studies from UPMC and the Roswell Park Comprehensive Cancer Center, in human tumor explants, have demonstrated that Ampligen is a TLR3 restricted and targeted immune modulator that can facilitate the transformation of some "cold" tumor microenvironments into "hot" tumor microenvironments (Cancer Res. 2018 Aug 1;78(15):4292-4302).

"At Hemispherx we are determined to pursue a comprehensive R&D program focused on improved immune therapies for lethal malignancies such as recurrent ovarian cancer. We at Hemispherx are deeply grateful for the attention and support we are getting from Merck and the world-class ovarian cancer team at UPMC in this important major clinical trial," said Hemispherx CEO Thomas K. Equels. "We believe this clinical study at UPMC is an important step in Hemispherx’ overall clinical plan in immuno-oncology and just one of the major milestones we have recently announced. We believe that the clinical trials that are now underway are very important to our company. We have seen a clear synergistic effect in our animal laboratory studies in several different solid tumors. Data from human tumor explants indicate this phenomenon may extend to humans. In addition to the already existing large IV safety profile, we have established that Ampligen is generally well tolerated intraperitoneally. To the extent this follows through in vivo with humans in these clinical trials, we believe the expected synergy with the checkpoint inhibitors in humans has the potential to position Ampligen as a medical translational breakthrough in immuno-oncology. We believe the Ampligen clinical data are important first and foremost to those in need of such enhanced immuno-therapeutic response in recurrent cancers as well as a long-term driver for stockholder value. "

Cautionary Statement

Some of the statements included in this press release may be forward-looking statements that involve a number of risks and uncertainties. Among other things, for those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements set forth in this press release speak only as of the date of this press release. Among other things, no assurance can be given as to whether the trial at UPMC or other ongoing or planned trials will be successful or yield favorable data and the trials are subject to many factors including lack of regulatory approval(s), lack of study drug, or a change in priorities at the sponsoring Universities or Cancer Centers. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.hemispherx.net. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.

On February 11, 2019 Greywolf Therapeutics, a drug discovery biotechnology company focused on immuno-oncology, reported it has completed a £10 million ($14 million) series A financing round with leading international healthcare investors Andera Partners and Canaan (Press release, Grey Wolf Therapeutics, FEB 11, 2019, https://www.greywolftherapeutics.com/news/gwt-completes-ps10m-14m-series-a-financing [SID1234650152]).

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Greywolf’s novel approach is aimed at directly altering tumour cells, illuminating them for attack and destruction by the immune system. The goal is to exploit this increased tumour visibility in monotherapy and to extend the therapeutic benefit of already approved immunotherapies to many more cancers.

Greywolf is developing small molecule modulators of endoplasmic reticulum aminopeptidases (ERAPs), key proteins in the antigen presentation pathway, to change the neoantigen repertoire in tumours and thereby increase the number and range of neoantigens presented on tumour cells available to engage an immune response.

This unique small molecule immuno-oncology approach builds on the exciting recent advances in cancer immunotherapies that address a key limiting factor for approved treatments, while avoiding the complex and costly personalisation required for other approaches such as neoantigen vaccines.

Greywolf has programs targeting the two homologues of ERAP, ERAP1 and ERAP2, aimed at developing potent and selective modulators, with the lead program being against ERAP1.

Greywolf was co-founded by Peter Joyce, former Project Leader at Vertex Pharmaceuticals, and Tom McCarthy, former President and CEO of Spinifex Pharmaceuticals, and comprises a team of world-leading experts in immuno-oncology, antigen presentation and drug discovery. It is working with the University of Oxford, University of Southampton and has a strategic partnership with Sygnature Discovery, a leading independent provider of drug discovery resources and expertise. Sygnature is also an investor in the Company.

Peter Joyce, Chief Executive Officer of Greyw‍olf Therapeutics, said: "The recent breakthroughs in immunotherapy have fundamentally changed the treatment landscape in oncology, but the fact remains that current approaches only target the minority of tumours that are visible to the immune system, whilst the vast majority of cancers do not respond. There is strong validation for targeting ERAPs to increase tumour visibility and with these funds we are now positioned to build on our existing work and collaborations to deliver a clinical candidate in the coming two to three years."

Tom McCarthy, Executive Chairman of Greywolf Therapeutics, said: "Attracting investors of the calibre of Andera and Canaan is a strong validation of the potential of our approach to broaden the effectiveness of immunotherapy. We believe we have a truly novel approach in targeting tumours themselves, rather than direct regulation of the immune system, and I am excited by the opportunity to work with our investors and talented team on the next steps of Greywolf’s development."

Thierry Hercend, Venture Partner at Andera Partners, said: "Greywolf has identified a highly innovative approach to immuno-oncology and, in Peter and Tom, has founders with very strong scientific and entrepreneurial credentials. With the support of Sygnature, they achieved a significant amount with their seed funding and demonstrated a scientifically rigorous and nimble approach to drug development which we value. I’m confident that with this series A financing, Greywolf will deliver on the full potential of ERAP modulation."

Brent Ahrens, General Partner at Canaan, said: "Greywolf marks Canaan’s first investment in the UK biotechnology sector, and we are excited by the Company’s science and its potential to help the huge numbers of patients yet to receive any benefit from current oncology treatment options."

Raphaël Wisniewski, Partner at Andera, Thierry Hercend, Venture Partner at Andera and Brent Ahrens, General Partner at Canaan have joined Greywolf’s Board of Directors.

On February 11, 2019 CTI BioPharma Corp. (NASDAQ:CTIC) reported that it has received a $10 million milestone payment from Teva Pharmaceutical Industries Ltd. related to the achievement of sales milestones for TRISENOX (arsenic trioxide) (Press release, CTI BioPharma, FEB 11, 2019, View Source;p=RssLanding&cat=news&id=2386868 [SID1234533209]). TRISENOX was acquired from CTI BioPharma by Cephalon, Inc. (Cephalon). Cephalon was subsequently acquired by Teva. The milestone was paid pursuant to an acquisition agreement for TRISENOX entered into with Cephalon under which CTI BioPharma is eligible to receive up to an additional $40 million in payments upon achievement by Teva of specified sales and development milestones related to TRISENOX.

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On February 11, 2019 Aduro Biotech, Inc. (NASDAQ: ADRO) reported that the first patient has been dosed in a Phase 1 trial of ADU-S100 (MIW815), a novel stimulator of interferon genes (STING) pathway activator, in combination with YERVOY (ipilimumab), an approved anti-CTLA-4 antibody for the treatment of relapsed and refractory melanoma (Press release, Aduro Biotech, FEB 11, 2019, View Source;p=RssLanding&cat=news&id=2386898 [SID1234533231]). The multicenter trial (see www.clinicaltrials.gov, identifier: NCT02675439), which is part of an ongoing research and development collaboration with Novartis, will enroll advanced melanoma patients who have relapsed after or are refractory to treatment with anti-PD-1 antibodies, nivolumab or pembrolizumab.

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"We are pleased to initiate this study evaluating ADU-S100 with ipilimumab in a homogeneous patient population. Despite recent advancements in treating earlier stages of melanoma, the relapsed and refractory patient segment remains underserved due to a lack of therapeutic options. Based on their potential synergistic activity, ADU-S100 in combination with an anti-CTLA-4 antibody could generate a systemic adaptive immune response in patients with late-stage melanoma," commented Stephen Isaacs, chairman, president and chief executive officer of Aduro Biotech. "As demonstrated leaders in the STING pathway, we are committed to build upon the growing body of data we’ve generated thus far, including encouraging clinical signals demonstrated by ADU-S100 as a single agent and in combination with spartalizumab, an investigational anti-PD-1 antibody."

The protocol for investigation of ADU-S100 as a single agent was amended to include evaluation of ADU-S100 in combination with ipilimumab. During the ongoing dose escalation phase of the trial, ipilimumab will be administered at its approved dose and schedule, while the dose of ADU-S100 will be escalated. The dose expansion phase of the trial will evaluate the optimized dose of ADU-S100 in combination with ipilimumab in two expansion cohorts that will enroll patients with cutaneously and viscerally accessible melanoma.

As previously presented at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, target engagement of ADU-S100 and activation of the STING pathway was demonstrated in the ongoing Phase 1 dose escalation of ADU-S100 alone through increases in key systemic cytokines, IL-6, MCP-1 and IFN- β after administration. Partial responses were observed in 4.9 percent of patients (n=2/41), including one patient with parotid gland cancer who received prior anti-PD-1 therapy. Stable disease (SD) was achieved in 26.8 percent of patients (n=11/41), including five patients who had received prior checkpoint inhibitor therapy. In the ongoing study of ADU-S100 in combination with spartalizumab, clinical responses were observed in several tumor types, including two patients who had previously demonstrated responses to checkpoint inhibitor therapy alone.

In preclinical models, activation of the STING pathway has been shown to rapidly invoke an innate immune response, which subsequently leads to a systemic and sustained adaptive immune response through tumor-specific-CD8+ T cells. Ipilimumab may further augment such immunity, by blocking the activity of the checkpoint protein, CTLA-4, resulting in enhanced activity of T cells that attack melanoma cells in the body, supported by the demonstration of combined activity of ADU-S100 and anti-CTLA-4 in preclinical models.

About STING Pathway Activator Technology
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Natural activation of STING is not always sufficient to prevent the growth and spread of cancer cells. In preclinical models, ADU-S100 directly activates STING to further amplify the natural anti-tumor response. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

Aduro’s lead molecule, ADU-S100, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial as a single agent and in combination with ipilimumab, and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. These studies are enrolling patients with cutaneously accessible, advanced/metastatic solid tumors or lymphomas. The trials are evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills distant metastases.

On February 11, 2019 3SBio Inc. ("3SBio") (HKEX:1530) and Verseau Therapeutics, Inc. ("Verseau") reported a partnership agreement focused on the development and commercialization of novel monoclonal antibodies in the field of immuno-oncology for a broad range of cancers (Press release, Verseau Therapeutics, FEB 11, 2019, View Source [SID1234542367]). Verseau’s proprietary drug discovery platform generates first-in-class macrophage checkpoint modulators (MCMs) to benefit patients with cancer, immune and inflammatory diseases.

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Under the terms of the agreement, 3SBio will receive an exclusive license to develop and commercialize a select number of MCM antibodies for all human oncology indications in Greater China, including mainland China, Taiwan, Hong Kong and Macau ("Territory"). Verseau will be responsible for discovery and optimization of MCM antibodies for each program. 3SBio will fund and conduct antibody development, GMP manufacturing, and commercialization in the Territory. Verseau and 3SBio will be eligible to receive certain milestone payments and royalties on product sales both in the Territory and globally. 3SBio will also purchase $15 million of Verseau Series B preferred stock. Additional financial terms were not disclosed.

"Recent advances in immuno-oncology have produced unprecedented benefit to patients; however, many people with cancer still require more effective treatment options," said Dr. Jing Lou, Chief Executive Officer of 3SBio. "Our collaboration with Verseau provides 3SBio with access to novel and differentiated immune-modulating antibodies that will complement our growing innovative oncology portfolio. We look forward to partnering with the Verseau team."

"3SBio is an ideal partner for Verseau to rapidly advance our novel, first-in-class macrophage checkpoint modulators in immuno-oncology," said Dr. Christine Bunt, Chief Executive Officer and Chairman of the Board of Verseau. "3SBio is a pioneer in China’s biotechnology industry with a fully-integrated R&D, manufacturing and commercial platform."

About Macrophage Checkpoint Modulators

Verseau is broadening the therapeutic potential of immunotherapy by developing macrophage checkpoint modulators (MCMs) that regulate the functional shift to make macrophages more inflammatory or more tolerogenic depending on the disease context. While PD-1 inhibitors have provided great clinical successes, they are only effective in 10-15% of cancer patients. Macrophages demonstrate one of the highest infiltration rates in human tumors (~75%). MCMs cause tumors to turn highly inflammatory and stimulate multiple immune cell types, including T cells. Verseau’s therapies have the potential to significantly expand the number of patients benefitting from immunotherapy, including those unresponsive to PD-1 inhibitor therapies. Through its proprietary all-human translational system Verseau has validated more than two dozen targets amenable to different therapeutic modalities, including monoclonal antibodies (mAbs).