On November 21, 2019 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next-generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported that it expanded its research collaboration with the Karolinska Institutet in Stockholm, Sweden (Press release, Phio Pharmaceuticals, NOV 21, 2019, View Source [SID1234551577]). The collaboration thus far has focused on the use of the Company’s self-delivering RNAi compounds against targets involved in T cell and NK cell differentiation and/or tumor-induced stress response, with the aim of producing anti-tumor adoptive cell therapy grafts with improved functionality and persistence. Based on compelling results, Phio Pharmaceuticals and Karolinska have agreed to extend and expand the collaboration to research aimed at decreasing immune-inhibitory factors in the tumor micro-environment and/or arming T cell, NK cell, dendritic cells and macrophages to overcome tumor immunosuppression utilizing Phio Pharmaceuticals’ INTASYL platform.

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This work will further align with ongoing translational research at the Karolinska Institutet, which combines adoptive T cell therapy and dendritic cell vaccination. The focus of the expanded collaboration will include developing a pathway to the clinic and establishing the utility of Phio Pharmaceuticals’ self-delivering RNAi in these therapeutic applications.

Dr. Gerrit Dispersyn, President and CEO of Phio Pharmaceuticals, stated, "Over the last year, our collaboration with Dr. Kiessling’s group at the Karolinska Institutet has led to exciting results with several compounds in both T cells and NK cells, including the results presented earlier this month at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting showing that INTASYL technology can be used to expand T cells with superior anti-tumor potential for adoptive cell therapies. Our continued collaboration will build upon these findings and expand to additional targets and cell types. We are very pleased to be working with Dr. Kiessling and his team on the advancement of our self-delivering RNAi immuno-oncology therapeutics towards clinical application in areas of Karolinska’s ongoing clinical research."

Rolf Kiessling, MD, PhD, Senior Professor in Experimental Oncology at the Karolinska Institutet, Senior Chief Physician at the Oncology clinic at the Karolinska University Hospital and member of Phio Pharmaceuticals’ Scientific Advisory Board stated, "Our results to date show that we can use self-delivering RNAi to modulate targets outside of checkpoints to improve efficacy of immune effector cells such as T cells and NK cells. The flexibility and ease of use of the platform means that we can also integrate this technology with other types of cells used in immuno-oncology therapy, including those that are currently being used in ongoing Karolinska clinical practice and clinical research."

On November 21, 2019 Azeria Therapeutics (Azeria), a newly formed pioneer factor drug discovery company, reported a £32 million Series B financing in which Syncona has committed £29.5 million alongside existing investor the CRT Pioneer Fund (Press release, Azeria Therapeutics, NOV 21, 2019, View Source [SID1234551575]).

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Azeria was originally founded in 2017 by Sixth Element Capital, manager of the CRT Pioneer Fund and Cancer Research UK’s Commercial Partnerships team with the aim of building a world class pioneer factor1 oncology company, developing breakthrough treatments for hormone resistant breast cancer patients. It was based on the work of leading expert in the field, Professor Jason Carroll at the Cancer Research UK Cambridge Institute, University of Cambridge, UK, whose scientific insights have led to a new approach to target FOXA1 driven cancer.

FOXA1 is an essential pioneer factor which has been shown to be pivotal in the tumour growth, progression and maintenance of oestrogen receptor positive luminal breast cancer. This is an area of significant unmet patient need where approximately 30 per cent of patients progress to late stage endocrine resistant disease2 and where there is potential for new treatments to have significant impacts for patients not addressed by existing therapeutics. Extensive target validation and drug discovery work to date supports the lead programme, with a plan to take the programme into the clinic over the course of the Series B funding. Azeria is seeking to develop the programme to commercialisation and to explore a pipeline of further programmes in oncology.

Azeria received initial investment of £5.5 million in Series A financing from the CRT Pioneer Fund, which focuses on early stage investments in highly innovative oncology programmes. Syncona is the largest investor in the CRT Pioneer Fund and will now participate directly in the next stage of growth and development. Magda Jonikas and Martin Murphy of Syncona will now join the Board of Azeria.

Stephen Myatt, Chief Executive Officer of Azeria Therapeutics said:

"Azeria is the product of more than ten years of research by Professor Jason Carroll at Cancer Research UK’s Cambridge Institute, University of Cambridge and was created to accelerate research and development into pioneer factors, a completely new target class in oncology including FOXA1. We would like to thank Sixth Element Capital for their continued support and look forward to working closely with Syncona to accelerate the development of breakthrough treatments for hormone resistant breast cancer patients."

Martin Murphy, Chief Executive of Syncona Investment Management Limited, said:

"Azeria is an exciting company and a perfect fit for Syncona’s long term strategy building globally leading healthcare companies. Based on unique, proprietary scientific insight, with a world class academic founder and high-quality team, the company has an opportunity to develop and commercialise treatments which could make a significant difference for patients. The Sixth Element team did an excellent job in identifying and investing in this science to take it to the point where it became an exciting and appropriate opportunity for Syncona."

1 A pioneer factor is a specialised type of transcription factor, able to ‘open’ compacted DNA to which is a protein that can initiate the expression of genes to make sure they are expressed in the right cell at the right time. Changes in these specific expression patterns can drives certain cancers.

On November 21, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a Phase 3-stage biopharmaceutical company discovering and developing novel products to treat cancer, with a focus on myelodysplastic syndromes (MDS), reported that it has priced a public offering of an aggregate of 55,000,000 shares of Onconova’s common stock (or common stock equivalents), together with accompanying common stock warrants, at a public offering price of $0.20 per share and associated warrant (Press release, Onconova, NOV 21, 2019, View Source [SID1234551574]). Each share of common stock (or common stock equivalent) was sold in the offering together with a common warrant to purchase one share of common stock at an exercise price of $0.20 per share. The common stock warrants are exercisable immediately and will expire five years from the date of issuance. The offering was led by healthcare dedicated funds and included officers and directors of Onconova.

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H.C. Wainwright & Co. is acting as exclusive placement agent for the offering.

The gross proceeds to Onconova from this offering are expected to be $11.0 million, before deducting the placement agent’s fees and other estimated offering expenses payable by Onconova, assuming none of the warrants to be issued in this offering are exercised. The offering is expected to close on or about November 25, 2019, subject to the satisfaction of customary closing conditions.

Onconova anticipates using the net proceeds from the offering to fund the development of its clinical and preclinical programs, for other research and development activities and for general corporate purposes, which may include capital expenditures and funding working capital needs.

The securities described above are being offered by Onconova pursuant to a registration statement (File No. 333-234360) previously filed with and declared effective by the Securities and Exchange Commission (the "SEC") on November 21, 2019. A preliminary prospectus relating to the securities being offered was filed with the SEC on November 21, 2019 and is available on the SEC’s website at View Source Electronic copies of the final prospectus relating to the offering may be obtained, when available, by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by calling (646) 975-6996 or by emailing [email protected] or at the SEC’s website at View Source

This announcement is neither an offer to sell, nor a solicitation of an offer to buy, any of these securities and shall not constitute an offer, solicitation or sale in any state or jurisdiction in which such offer, solicitation or sale is unlawful. Any offer, if at all, will be made only by means of the prospectus forming a part of the effective registration statement.

On November 21, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a Phase 3-stage biopharmaceutical company discovering and developing novel products to treat cancer, with a focus on myelodysplastic syndromes (MDS), reported they have entered into a Distribution, License and Supply Agreement with Knight Therapeutics Inc. ("Knight"), a Canadian-based specialty pharmaceutical company focused on acquiring, in-licensing, selling and marketing innovative prescription and over-the-counter pharmaceutical products, whereby Knight shall have the exclusive rights to commercialize rigosertib in Canada (Press release, Onconova, NOV 21, 2019, View Source [SID1234551573]). In addition, Onconova may be entitled to receive clinical, regulatory and sales-based milestone payments up to CAD 33.95 million and tiered double-digit royalties on net sales.

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"We are pleased to add Knight to our roster of global partners for rigosertib," said Dr. Steven Fruchtman, President and Chief Executive Officer of Onconova. "We are eager to work with Knight’s team, which has successfully partnered with a number of biotechnology companies to commercialize innovative medicines in Canada."

"Patients with high-risk MDS have limited treatment options after first-line hypomethylating agents such as azacitidine fail," said Jonathan Ross Goodman, Chief Executive Officer of Knight. "If approved, rigosertib would address this unmet need and we look forward to the results of the ongoing phase III INSPIRE trial of IV rigosertib."

About Myelodysplastic Syndromes

MDS is a group of blood disorders that affect bone marrow function, whereby the bone marrow cells appear dysplastic and their capacity to produce cells is defective. As a result, patients with MDS have low blood cell counts and require frequent blood transfusions. In approximately one-third of patients, higher-risk MDS can progress to acute myelogenous leukemia (AML).

The Leukemia and Lymphoma Society of Canada estimates that there are between 1,800 and 5,900 new cases of MDS diagnosed in Canada each year. MDS is typically diagnosed in older individuals, and most patients diagnosed with the disease are over the age of 60. Approximately 23% of cases can be classified as having high risk or very high risk MDS as per the revised International Prognostic Scoring System (IPSS-R)1.

About Rigosertib

Rigosertib, Onconova’s lead candidate, is a proprietary Phase 3 small molecule. A key publication in a preclinical model demonstrated rigosertib’s ability to block cellular signaling by targeting RAS effector pathways (Divakar, S.K., et al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling." Cell 165, 643). Onconova is currently in the clinical development stage with oral and IV rigosertib, including clinical trials studying single agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in first-line and refractory higher-risk MDS patients (Phase 2). Patents covering oral and injectable rigosertib have been issued in the US and are expected to provide coverage until at least 2037.

About the INSPIRE Phase 3 Clinical Trial

The clinical trial INternational Study of Phase 3 IV RigosErtib, or INSPIRE, was finalized following guidance received from the U.S. Food and Drug Administration and European Medicines Agency. INSPIRE is a global, multi-center, randomized, controlled study to assess the efficacy and safety of IV rigosertib in higher-risk MDS (HR-MDS) patients who had progressed on, failed to respond to, or relapsed after previous treatment with a hypomethylating agent (HMA) within nine cycles over the course of one year after initiation of HMA treatment. This time frame optimizes the opportunity to respond to treatment with an HMA prior to declaring treatment failure, as per NCCN Guidelines. Patients are randomized at a 2:1 ratio into two study arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival. The trial continued beyond the pre-specified interim analysis and is nearing its conclusion. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).

On November 21, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematologic diseases and cancers, reported positive Phase 1b/2 results from an ongoing study in patients with IDH1-mutated gliomas (Press release, Forma Therapeutics, NOV 21, 2019, View Source [SID1234551571]). The data, presented at the 2019 Society for NeuroOncology Annual Meeting (SNO), demonstrate blood-brain barrier penetrance, as exhibited by cerebrospinal fluid exposure, and disease response to olutasidenib, a next-generation IDH1m inhibitor.

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"The safety profile and clinical activity observed to date with olutasidenib in patients with recurrent and often life-threatening gliomas are exciting," said Patrick Kelly, M.D., chief medical officer at FORMA Therapeutics. "In patients with a predominantly enhancing relapsed/refractory glioma, we achieved a clinical response with half of the patients still on study treatment at four months. Particularly for patients with late-stage gliomas where the disease progresses quickly, maintaining disease control holds promise."

FORMA is conducting a Phase 1b/2 study evaluating the safety, efficacy and pharmacokinetics/pharmacodynamics of olutasidenib for patients with advanced solid tumors and gliomas. The trial, 2102-ONC-102, is an open-label, single-agent dose-confirmation study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma and other IDH1 mutant solid tumors). Results announced today are based on continuous oral treatment for 24 patients with advanced IDH1 mutant glioma.

"These data create a compelling profile for olutasidenib as a next generation IDH1m inhibitor," said Frank Lee, chief executive officer of FORMA Therapeutics. "Our goal at FORMA is to offer patients first-in-class and best-in-class medicines, and the early results announced today bring us closer to this goal."

Phase 2 of FORMA’s study is ongoing, evaluating both olutasidenib monotherapy and olutasidenib in combination with azacitidine in patients with confirmed IDH1 gene-mutated advanced glioma. Full study results will be reported in 2020.

Presentation Overviews

Phase 1b/2 study of FT-2102, an inhibitor of mutant IDH1, in patients with relapsed/refractory IDH1 mutant gliomas: preliminary safety and clinical activity

E-talk Presentation by Macarena de la Fuente, M.D., Sylvester Cancer Center, University of Miami

Findings presented regarding olutasidenib monotherapy in the Phase 1 cohort of 24 patients with confirmed IDH1 gene-mutated advanced glioma, the majority of which were enhanced and high-grade glioma. Dr. de la Fuente discusses data that:

Demonstrate blood-brain barrier penetration as measured by cerebrospinal fluid exposure and disease control;
Confirm partial response in one patient and stable disease in 10 patients with enhancing glioma with a median duration of treatment of 3.7 months;
Indicate steady-state olutasidenib plasma concentrations in glioma patients within two weeks of initiation of dosing, which remained consistent over time;
Demonstrate acceptable safety profile in patients with relapsed/refractory IDH1-mutated glioma at 150 mg BID; and
Report no trial discontinuations due to treatment-emergent adverse events (TAEs). Grade 3-4 TAEs in greater than 10 percent of patients included increased ALT, increased AST, decreased platelet count, vomiting and hemiparesis. Transaminase elevations resolved without consequential impact in all patients.
FT-2102 – A Potent and Selective Brain Penetrant Inhibitor of Mutant Isocitrate Dehydrogenase

Oral presentation by Maria Ribadeneira, Ph.D., executive director of DMPK and clinical pharmacology at FORMA Therapeutics

Data demonstrate broad in vitro activity against the major IDH1-R132 mutations observed in glioma. Olutasidenib was observed to be more than 1000-fold selective in R132H, the more common mutation observed in glioma, as compared to IDH1 wild type, and showed potent in vivo suppression of tumor 2-HG in a mouse xenograft (cellular accumulation of 2-HG impairs cell differentiation and promotes tumorigenesis). Data also show olutasidenib to be highly brain penetrant in a rat model.

About Olutasidenib (FT-2102)

FORMA Therapeutics’ most advanced clinical asset, olutasidenib, is designed to be a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) to treat patients with relapsed/refractory acute myeloid leukemia (R/R AML) or myelodysplastic syndrome (MDS), as well as patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells; when mutated, its activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML and more than 70% of patients with gliomas. In gliomas, IDH1 mutations occur early in the tumor pathogenesis and persist throughout progression from a neural stem or progenitor cell. Gliomas are the most common, aggressive and difficult-to-treat primary brain tumors, and high-grade gliomas are associated with poor long-term prognosis, with a median survival ranging from five to seven years. Treatment options for relapsed glioma are limited.