On March 18, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported preliminary antigen-specific immune response data from a Phase 2 randomized investigator-sponsored trial (IST) of nelipepimut-S (NPS) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in women with ductal carcinoma in situ (DCIS) of the breast who are HLA-A2+ or A3+ positive, express HER2 at IHC 1+, 2+, or 3+ levels, and are pre- or post-menopausal (Press release, Sellas Life Sciences, MAR 18, 2020, View Source [SID1234555668]).

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"We are pleased to report preliminary results from the National Cancer Institute-sponsored Phase 2 VADIS trial, showing NPS is capable of inducing an antigen-specific antitumor immune response in DCIS patients even after a single vaccination, which is particularly encouraging," said Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Based on the immunobiological mechanism of action of NPS, we believe that NPS could be synergistic with standard therapies or novel immunotherapeutic approaches in women with DCIS. Moreover, these data correlate to previous findings of NPS in patients with invasive (non-DCIS) breast cancer. Given NPS’ low toxicity burden and high antigen-specific immune response, further clinical study of NPS as a therapeutic which could address the medical need of women with DCIS at an early stage of their therapeutic journey is likely warranted and these data further support our business development efforts to seek out-licensing opportunities to fund and conduct the future clinical development of NPS in order to maximize the potential of the program."

The study enrolled 13 patients, with nine patients receiving NPS plus GM-CSF and four patients receiving GM-CSF only. The relative frequency of NPS-specific CD8 cytotoxic T-lymphocytes as a percentage (NPS-CLT%) was twice as large in the NPS-treated patients. The NPS-CLT% was measured in the peripheral blood by a sensitive and specific assay using dextramer staining followed by flow cytometry, both at baseline (before vaccination or GM-CSF) and at 30 (+/-7) days after surgery. The mean difference in NPS-CTL% increase between the active and control groups was +0.10% vs +0.05%. The relative magnitude of change in NPS-CTL% mean values in NPS-treated patients over time was an 11-fold increase, from 0.01% at baseline to 0.11% after surgery, indicating a continued antigen-specific T-cell response post-NPS vaccination. NPS was generally well-tolerated in the study with no drug-related unexpected serious adverse reactions. The overall adverse event profile was consistent with previous safety data.

The final data is being further analyzed by the National Institute of Health, MD Anderson Cancer Center and the study principal investigator, Dr. Elizabeth Mittendorf, MD, PhD of the Dana-Farber/Brigham and Women’s Cancer Center, and will be presented at an upcoming medical conference.

"The preliminary data from the VADIS study showing a doubling of the difference in increase in antigen-specific CD8 cytotoxic T-lymphocytes in NPS-treated patients vs. controls, even with a single NPS inoculation, indicate in vivo immunogenicity of this cancer vaccine in DCIS. These data, as well as the previously reported clinical effects of NPS in the adjuvant setting after frontline therapy for invasive breast cancer, provide support for the possibility that NPS may be able to decrease the rate of recurrences in earlier-stage disease, such as DCIS, which I believe should be studied formally in future clinical studies," said Dr. Mittendorf. "While additional analyses of certain histologic and molecular markers of the patients’ immune responses against the NPS and other HER2 antigenic epitopes are currently ongoing, these initial immunobiological results from the VADIS study are encouraging."

About the Phase 2 VADIS Trial

This Phase 2 randomized trial is sponsored and operationalized by the National Cancer Institute (NCI) to study NPS’ potential clinical effects in earlier-stage disease. Patients are randomized to receive, prior to surgery, either GM-CSF followed by NPS two weeks later or GM-CSF alone. The primary endpoint of the trial is the difference in the frequency of newly induced NPS-cytotoxic T lymphocytes (CTL; CD8+ T-cell) in peripheral blood between the two arms of the study, using a dextramer assay. Secondary endpoints to be compared between the two arms include the nature and incidence of adverse events and in vivo immune response to NPS, in addition to other select histologic and molecular biomarkers.

About DCIS

DCIS is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct and have not spread outside the duct to other tissues in the breast. DCIS is the most common type of breast neoplasm with malignant potential. In some cases, DCIS may become invasive cancer and spread to other tissues and, currently, it is not possible to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. Tamoxifen is given in cases with hormone receptor positivity only. No targeted or immune therapies have shown any definitive clinical activity in DCIS to date. The current standard treatment aims at forestalling the progression of DCIS to invasive cancer. In approximately 15-25% of cases progression does occur. DCIS is diagnosed in more than 60,000 women each year in the United States, comprising 1 in 5 newly diagnosed cases of breast cancer.

On March 18, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a focus on myelodysplastic syndromes (MDS), reported that the Company will release its year-end 2019 financial results on Tuesday, March 24, 2020, after the market closes (Press release, Onconova, MAR 18, 2020, View Source [SID1234555667]). Management will host a conference call and live webcast at 4:30 p.m. ET on the same day to discuss these results and provide an update on its pipeline programs.

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Interested parties who wish to participate in the conference call may do so by dialing (855) 428-5741 for domestic and (210) 229-8823 for international callers and using conference ID 3267259. Those interested in listening to the conference call live via the internet may do so by visiting the investors’ page of the company’s website at www.onconova.com and clicking on the webcast link.

A webcast replay will be available on the Onconova website for 90 days following the call by visiting the investor page of the company’s website at www.onconova.com

On March 17, 2020 LifeArc has joined leading UK venture capital firm UK Innovation & Science Seed Fund (UKI2S) in investing into GyreOx Therapeutics (GyreOx). The funding will support a two-year programme to develop and automate GyreOx’s proprietary drug discovery platform, MACRO (Press release, LifeArc, MAR 17, 2020, View Source [SID1234555736]).

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The MACRO platform generates a range of highly modified macrocyclic peptide molecules, known as gyrocycles, which can penetrate cells and be targeted to tackle the protein-protein interactions (PPI) within. These intracellular processes are potentially implicated in many health conditions including cancer, inflammation and autoimmune diseases and are difficult to reach with currently available medicine classes. Automation of the MACRO platform will enhance the generation process further to allow a greater number of novel macrocycles to be generated more quickly and more cheaply.

Dr Bill Primrose, Founder and CEO of GyreOx said: "It’s a strong endorsement of our technology that we have been able to attract support from such quality investors. We have an ambitious plan to develop the platform and to deploy it on a number of internal programmes, including one targeting an epigenetic cancer target. It is our ambition to make GyreOx into a clinical stage company with a strong drug pipeline and a number of discovery alliances with major players in the pharmaceutical industry."

Common medicines classes include small molecules and biologics. While small molecules can enter cells to modulate intracellular process, they have difficulty in addressing complex targets, including PPIs. Biologics, such as humanised antibodies, are unable to enter the cell and are therefore only suitable for addressing drug targets on the cell surface. GyreOx’s Gyrocycle highly modified macrocyclic peptides combine the targeting ability of biologics with the cell-entry ability of small molecules; these molecules present an attractive, novel therapeutic modality as they can also be engineered to further improve their pharmacokinetic profile and ability to penetrate cells to reach previously "undruggable" targets.

Dr David Holbrook, Head of Seed Fund, LifeArc said: "The LifeArc Seed Fund is delighted to be supporting GyreOx on its work on the macrocycles platform and helping translate the science on the next step towards the patient. GyreOx is a great example of the type of company we are trying to support—great science, great scientists, strong start up management all addressing a significant unmet health need."

On March 17, 2020 Circle Pharma, Inc., a macrocycle drug discovery and development company focused on intractable cancer targets, reported that it has raised $45 million in a Series B financing (Press release, ShangPharma Innovation, MAR 17, 2020, View Source [SID1234555735]).

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The financing was led by The Column Group, with participation by Nextech Invest. All investors from the prior round – ShangPharma, LifeForce Capital, and the Berkeley Catalyst Fund – joined the financing.

In conjunction with the financing, Peter Svennilson, founder and managing partner of The Column Group, and Thilo Schroeder, Ph.D., partner at Nextech Invest were appointed to the board. John Josey, Ph.D., formerly President and CEO of Peloton Therapeutics, was appointed to the board as Chairman.

Proceeds from the investment will be used to advance Circle’s work to develop inhibitors of Cyclin A and Cyclin E, and to expand the company’s pipeline.

"We are delighted to have these premier life science investors supporting our Series B financing," said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "With this strong backing, we will expand our team, drive our cyclin targeted programs towards the clinic, and apply our macrocycle platform to additional intractable targets."

Circle’s new board appointments:

Peter Svennilson is the founder and managing partner of The Column Group. He was the chairman of Aragon Pharmaceuticals (acquired by Johnson & Johnson) and Seragon Pharmaceuticals (acquired by Roche / Genentech) and was a board director of Gritstone Oncology, NGM Biopharmaceuticals, Immune Design and Constellation Pharmaceuticals. He is currently a board director of ORIC Pharmaceuticals, Ribon Therapeutics and Carmot Therapeutics.

Thilo Schroeder, Ph.D., is a partner at Nextech Invest, a Zurich-based oncology-focused investment firm. He previously served on the board of Peloton Therapeutics (acquired by Merck) and Blueprint Medicines. He is currently a board director at IDEAYA Biosciences, Revolution Medicines, PMV Pharma, Silverback Therapeutics and a board observer at Black Diamond Therapeutics.

John Josey, Ph.D., served as the President, Chief Executive Officer, and member of the Board of Directors at Peloton Therapeutics from 2013 until its acquisition by Merck in 2019. From 2011 to 2013, he was President and Chief Scientific Officer at Peloton, and from 1998 to 2011, Vice President of Discovery Chemistry at Array Pharma.

The continuing members of Circle’s board of directors are Walter H. Moos, Ph.D., CEO of ShangPharma Innovation and Managing Director of Pandect Bioventures, Matthew P. Jacobson, Ph.D., Circle Pharma co-founder, chair of the department of pharmaceutical chemistry at U.C. San Francisco and also co-founder of Global Blood Therapeutics, Relay Therapeutics and Cedilla Therapeutics, and David J. Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma.

On march 17, 2020 Oncotarget reported the cover for issue 11 of Oncotarget features Figure 6, "Effects of AZD8186 in combination with anti-PD1 on syngeneic models," by Owusu-Brackett, et al.

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In vitro cell viability assay and immunoblotting demonstrated that PTEN loss was significantly correlated with AZD8186 sensitivity in triple-negative breast cancer cell lines.

AZD8186 in combination with paclitaxel, eribulin had synergistic effects on growth inhibition in PTEN loss cells.

AZD8186 significantly enhanced the antitumor efficacy of anti-PD1 antibodies in the PTEN-deficient BP murine melanoma xenograft model, but not in the PTEN-wild-type CT26 xenograft model.

In vitro, cell proliferation and colony formation assays were performed to determine cell sensitivity to AZD8186.

AZD8186 has single-agent efficacy in PTEN-deficient TNBC cell lines in vitro but has limited single-agent efficacy in vivo.

Dr. Funda Meric-Bernstam from the Department of Surgical Oncology, the Department of Investigational Cancer Therapeutics, the Department of Breast Surgical Oncology, as well as The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at The University of Texas MD Anderson Cancer Center, in Houston, Texas, USA said, "Phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is an important regulator of many physiological cellular processes that promote differentiation, proliferation and survival of a normal cell."

"Phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is an important regulator of many physiological cellular processes that promote differentiation, proliferation and survival of a normal cell."

– DR. FUNDA MERIC-BERNSTAM, DEPARTMENT OF INVESTIGATIONAL CANCER THERAPEUTICS, THE DEPARTMENT OF BREAST SURGICAL ONCOLOGY & THE SHEIKH KHALIFA BIN ZAYED AL NAHYAN INSTITUTE FOR PERSONALIZED CANCER THERAPY

Mutations, loss of copy number, epigenetic silencing and downregulation of PTEN protein by mi RNA can result in PTEN function inactivation, leading to activation of PI3K/AKT/mTOR pathway, which subsequently increases tumor growth, invasion and metastasis across a diverse set of solid tumors including breast, endometrial, prostate, renal cell, hepatocellular, glioblastoma, and colorectal cancers.

Loss of PTEN and increased PI3K signaling are associated with resistance to trastuzumab and endocrine therapy in hormone receptor-positive breast cancer and with poor prognosis in triple-negative breast cancers.

In vitro, they revealed significant growth inhibition of PTEN-deficient tumors by depleting PIK3CB which encodes PI3K, while no such growth inhibition effect was shown in corresponding PTEN-deficient tumors with downregulation of PIK3CA or PIK3CD encoding PI3K and PI3K, respectively.

Thus, PI3K isoform is the driver of abnormal proliferation in PTEN-null cancers, and as such, PI3K is a promising target for therapy in PTEN-deficient TNBC. AZD8186 is a selective and potent small-molecule inhibitor of PI3K, with additional activity against PI3K isoform.

The Meric-Bernstam Research Team concluded in their Oncotarget Research Paper, "these results provide preclinical evidence of antitumor efficacy of AZD8186 in PTEN-deficient solid tumors. AZD8186 has single-agent efficacy in PTEN-deficient TNBC cell lines in vitro, with modest single-agent efficacy in vivo. Furthermore, AZD8186 enhanced the antitumor efficacy of paclitaxel but stable and progressive disease were noted with this combination in immunosuppressed models. In immunocompetent models, AZD8186 in combination with anti-PD1 resulted in tumor regression in PTEN-deficient BP tumor. We realize that while there appears to be an association of AZD8186 sensitivity to PTEN loss, a cause-effect relationship can only be speculated on. In summary, although further insights are needed into the mechanisms of activity of these combinations, the combination of AZD8186 with taxanes and with anti-PD1 agents hold promise for the treatment of PTEN-deficient solid tumors."