Swiss Group for Clinical Cancer Research

Preclinical data on roginolisib, an oral first-in-class non-ATP competitive allosteric modulator of PI3Kδ, for the potential treatment of solid and hematological tumors GENEVA and AMSTERDAM, March 16, 2023 /PRNewswire/ -- iOnctura, a clinical stage biotechnology company developing breakthrough therapies for patients suffering with cancer, today announces the publication of non-clinical research on roginolisib in the AACR journal Cancer Research Communications. Roginolisib is a first-in-class, non-ATP-competitive, allosteric modulator of PI3Kd which prevents tumor proliferation and breaks immune tolerance in patients with solid and hematological tumors. PI3Kδ inhibition in solid tumors has recently emerged as a novel approach to treating cancer because of its potential in targeting multiple tumor survival pathways. First-generation PI3Kδ inhibitors are used to treat hematological tumors, but safety concerns and limited target selectivity have curbed their clinical usefulness. Safety concerns are even more aggravated in patients with solid malignancies where rapid onset of toxicities have been observed. Conversely, roginolisib has a favorable toxicity profile with less than 5% Grade 3/4 toxicities at the biologically effective dose. Importantly, these toxicities were transient in nature without the need for dose reductions. The research published in Cancer Research Communications reinforces the conclusion that roginolisib inhibits regulatory T cell proliferation while having limited anti-proliferative effects on conventional CD4+ T cells and no effect on CD8+ T cells. This process unveils the tumor to the immune system whilst retaining normal immune function. Importantly, treatment of CD8+ T cells with roginolisib during activation favors the differentiation of memory-like, long-lived CD8+ T cells, known to have increased antitumor capacity. Consistent with first-generation PI3Kd inhibitors, roginolisib inhibits the in vitro growth of lymphoma cells. In contrast to these other PI3Kd inhibitors, roginolisib activity is correlated with the expression levels of PIK3CD, suggesting cancer cell-intrinsic effects of the drug. Professor Francesco Bertoni, Head of the Lymphoma Genomics group at Institute of Oncology Research in Bellinzona, Switzerland, said: "This research differentiates roginolisib from other PI3Kd inhibitors and adds to the growing body of nonclinical and clinical evidence that modulation of PI3Kd through an allosteric non-ATP competitive mechanism can be achieved safely and effectively." The research also highlights roginolisib has immune-modulatory properties that can be exploited in solid tumors. In CT26 colorectal and LLC lung cancer models, roginolisib sensitized the tumors to anti-PD-1 (Programmed cell death protein 1) treatment, with similar activity in the Pan-02 pancreatic and A20 lymphoma syngeneic mouse models. Roginolisib reshaped the balance of tumor infiltrating cells, favoring infiltration of CD8+ and NK cells, while decreasing suppressive immune cells. Roginolisib presented no safety concerns in animal studies, or in Phase I human studies, and is currently in clinical Phase Ib/II investigation in solid and hematological tumors. Catherine Pickering, Chief Executive Officer of iOnctura, said: "We are excited that our ground-breaking research has been published by Cancer Research Communications highlighting the potential of our lead clinical program, roginolisib in both solid and hematological cancers. We anticipate returning this key anti-tumor mechanism to physician's tool-boxes for hematological cancers as well as offering new value for patients with solid tumors." The research was published in the open access peer-reviewed journal Cancer Research Communications, part of the prestigious AACR stable of journals, which aims to accelerate the pace of discovery and stimulate innovation in cancer science, by giving rapid open publication of hypotheses, methods, results, data resources and cutting-edge knowledge. About iOnctura iOnctura is a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways such as cellular proliferation; escape from immune detection; and drug resistance. iOnctura's pioneering approach to drug development is expected to offer significant clinical benefits over the traditional approach of targeting a single pathway alone. iOnctura has progressed two therapeutic candidates into mid-stage clinical development: IOA-244 (proposed name roginolisib), a first-in-class allosteric modulator of PI3Kδ; and IOA-289, a highly selective, non-competitive autotaxin (ATX) inhibitor. iOnctura is backed by specialist institutional investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. About roginolisib Roginolisib is a first-in-class non-ATP competitive, small molecule, allosteric PI3Kδ modulator. Its unique structural and selectivity features drive a unique way of inhibiting PI3Kδ which translates into a highly beneficial tolerability and clinical benefit profile. PI3Kδ over-expression stimulates multiple cancer mechanisms and has an oncogenic role in many tumor types. Roginolisib has a multi-modal effect on cancer; directly preventing cancer cell proliferation, harnessing an anti-tumor immune response via an effect on regulatory T-cells and cytotoxic T cells and potentiating the effect of immunotherapy. Roginolisib is currently in the cohort expansion phase of the DIONE-01 trial, a two-part, first-in-human dose study evaluating roginolisib in advanced cancers and as a combination partner for conventional and immune- therapies (NCT04328844). About Professor Francesco Bertoni Prof. Francesco Bertoni is the head of the Lymphoma Genomics group at Institute of Oncology Research in Bellinzona, Switzerland, the Institute deputy director, and Adjunct Professor at the Università della Svizzera italiana (USI). Prof. Bertoni's research topics are the development of new anti-lymphoma compounds and lymphoma genomics. He actively participates in the Swiss Cancer Research Group (SAKK), where he is the President of the Project Group Lymphoma and member of the Project Group Developmental Therapeutics. Prof. Bertoni is the author or co-author of over 200 original papers, over 50 editorials or invited reviews, 20 book sections, one edited book and several abstracts at national and international meetings. SOURCE iOnctura

Findings shared in an oral presentation at ASTRO Annual Meeting 2022 suggest predictive biomarker could help guide treatment in men experiencing disease progression after surgery SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Veracyte, Inc. (Nasdaq: VCYT) announced new data demonstrating that a genomic signature derived from the company’s Decipher GRID database could help determine which men experiencing prostate cancer progression following radical prostatectomy (RP) would benefit from dose-intensified salvage radiotherapy (SRT). The data, from a randomized, phase 3 trial, were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2022 (abstract #160) taking place October 23-26, 2022, in San Antonio, Texas. Post-Operative Radiation Therapy Outcomes Score (PORTOS) is a gene-expression signature of 24 DNA damage, repair and immune pathway genes previously shown to predict benefit from postoperative radiotherapy. In the current study, researchers evaluated the biomarker’s predictive ability for SRT dose among 226 men in the prospective open-label, multicenter, randomized phase 3 Swiss Group for Clinical Cancer Research (SAKK) 09/10 trial. This trial, which randomized men with biochemically recurrent disease after RP to conventional or dose-intensified salvage radiotherapy without the addition of androgen deprivation therapy (ADT), did not report a clinical benefit for dose-intensification. The new data shared at ASTRO show that the subset of men with higher PORTOS scores had substantial improvement in clinical-progression-free survival (CPFS) with the higher dose of SRT (70Gy). Specifically, those men with higher PORTOS scores had an absolute benefit of 45% CPFS at 5 years with dose-intensified SRT compared with the standard dose, while the men with lower PORTOS scores had an absolute benefit of -10% (p-interaction=0.003). “Our findings suggest that the Decipher PORTOS signature may be a valuable tool to help physicians better identify those prostate cancer patients who should receive dose-intensified salvage radiotherapy when their disease recurs following radical prostatectomy,” said Alan Dal Pra, M.D., member of Sylvester Comprehensive Cancer Center, director of Clinical Research and associate professor of radiation oncology at the University of Miami Miller School of Medicine, and lead author on the ASTRO abstract. “Dependent on further studies, this could be the first predictive biomarker to help physicians personalize radiotherapy dose in the postoperative prostate cancer setting.” It is estimated that up to 40 percent of men with intermediate- or high-risk prostate cancer may experience a biochemical disease recurrence after RP, which is characterized by rising levels of serum prostate-specific antigen (PSA).1 For those men who experience a rising PSA, treatment with 64-72 Gy SRT is now standard of care, though treatment with higher doses can lead to greater urinary and bowel side effects. “This study demonstrates how gene-expression signatures can help identify the men who are most likely to benefit from more radiation, and help inform physician and patient decisions regarding their radiation treatment after surgery,” said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. “We very much value our multi-year research efforts with the Swiss SAKK study group, and look forward to our continued collaborations with leading academic and industry partners to further validate GRID-derived predictive biomarkers that may help physicians better individualize the care of men with prostate cancer.” About Decipher GRID The Decipher Genomics Resource for Intelligent Discovery (GRID) database includes more than 100,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its research partners to help advance understanding of prostate and other urologic cancers. PORTOS is among more than 400 biomarkers that have been discovered or developed using Decipher GRID and are available on a Research Use Only basis to physicians who have ordered the Decipher Prostate Genomic Classifier. About Veracyte Veracyte (Nasdaq: VCYT) is a global diagnostics company that improves patient care by answering important clinical questions to inform diagnosis and treatment decisions. Our growing menu of advanced diagnostic tests help patients avoid risky, costly procedures and interventions, and reduce time to appropriate treatment. In addition to making our tests available in the United States through our central laboratories, our exclusive license to our best-in-class diagnostics instrument (nCounter Analysis System) positions us to deliver our tests to patients worldwide through laboratories that can perform them locally. Veracyte is based in South San Francisco, California. For more information, please visit and follow the company on Twitter (@veracyte). Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to our statements related to our plans, objectives, expectations (financial and otherwise) or intentions with respect to our clinical tests in and outside of the United States. Forward-looking statements can be identified by words such as: “appears,” "anticipate," "intend," "plan," "expect," "believe," "should," "may," "will," “positioned,” “designed” and similar references to future periods. Examples of forward-looking statements include, among others, that the Decipher PORTOS signature may be a valuable tool to help physicians better identify those prostate cancer patients who should receive dose-intensified salvage radiotherapy when their disease recurs following radical prostatectomy, and that GRID-derived predictive biomarkers may help physicians better individualize the care of men with prostate cancer. Additional factors that may impact these forward-looking statements can be found under the caption “Risk Factors” in our Annual Report on Form 10-K filed on February 28, 2022, and our Quarterly Report on Form 10-Q to be filed for the three months ended June 30, 2022. Copies of these documents, when available, may be found in the Investors section of our website at . These forward-looking statements speak only as of the date hereof and, except as required by law, we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise. Veracyte, the Veracyte logo and Decipher are registered trademarks of Veracyte, Inc. and its subsidiaries in the U.S. and selected countries. Veracyte delivers the Decipher Prostate Genomic Classifier from its CLIA laboratories. Those tests are not CE-IVD marked and have not been cleared or approved by the FDA; their performance characteristics were determined by Veracyte and they might be considered for Research Use Only in some markets. Please contact Veracyte for confirmation. This piece is distributed purely for educational purposes and is not intended to promote or encourage any off-label use of Veracyte products. 1 Tourinho-Barbosa R, et al. Biochemical recurrence after radical prostatectomy: what does it mean? Int Braz J Urol. 2018 Jan-Feb;44(1):14-21. doi: 10.1590/S1677-5538.IBJU.2016.0656.