Roginolisib

Phase II study in non-small-cell-lung-cancer (NSCLC) to be run in collaboration with the ETOP IBCSG Partners Foundation across sites in Europe Study will investigate dostarlimab + roginolisib +/- docetaxel in patients with NSCLC resistant to first-line checkpoint inhibitor therapy GENEVA and AMSTERDAM, July 9, 2024 /PRNewswire/ -- iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, today announces expansion of the clinical trial program for lead pipeline asset, roginolisib. Via clinical collaboration agreements with the ETOP IBCSG Partners Foundation and GSK, roginolisib will be evaluated in combination with dostarlimab in NSCLC. Roginolisib is an allosteric modulator of PI3Kδ, widely recognized as a 'master switch' of cancer. Inhibition of PI3Kδ unleashes a multi-pronged anti-tumor and immune response to combat the tumor1 . Roginolisib has demonstrated an unprecedented clinical profile in solid and liquid cancers2, with 44 patients treated to date. Emerging clinical and translational biomarker data supports the hypothesis that combining roginolisib with a programmed death receptor-1 (PD-1) targeting agent, with or without docetaxel, may prevent or reverse drug resistance in NSCLC and may show synergistic anti-tumor immune activity without significant addition of toxicity3. Dostarlimab is a PD-1-blocking antibody approved for certain patients with endometrial cancer, which has also demonstrated clinical activity in combination with chemotherapy in NSCLC4. Under the terms of the agreement with iOnctura, GSK will supply dostarlimab for use in a randomized Phase II clinical trial in NSCLC patients resistant to first-line checkpoint inhibitor therapy, with or without docetaxel. iOnctura will retain worldwide rights to roginolisib. The ETOP IBCSG Partners Foundation is a leading organization performing international clinical and translational research in thoracic malignancies and breast cancer. Through the clinical collaboration, iOnctura will be provided access to a network of highly experienced investigators for the Phase II study. Professor Solange Peters, MD, PhD, Chair of Medical Oncology and the Thoracic Malignancies Programme in the Department of Oncology at the University Hospital of Lausanne will be the primary coordinating investigator of the study. Catherine Pickering, Chief Executive Officer of iOnctura, said: "As iOnctura moves into the next phase of clinical development, we are thrilled to be able to assess the effectiveness of roginolisib in combination with dostarlimab for the treatment of NSCLC. The successful uveal melanoma data reported so far, combined with a rich preclinical data package, support the rationale to expand our development program with potentially synergistic combinations in NSCLC." Solange Peters, Professor and Chair of Medical Oncology & Thoracic Malignancies Programme in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland, commented: "On behalf of the ETOP IBCSG Partners Foundation, we are intrigued by the benefit/risk profile of roginolisib. In patients who no longer respond to current therapies, we wish to investigate whether roginolisib in combination with dostarlimab provides a novel treatment option. ETOP IBCSG Partners Foundation is committed to investigate novel treatment options to help our patients." About iOnctura iOnctura is a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers with precision oral small molecules that target cancers in novel ways. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Two therapeutic candidates have progressed into mid-stage clinical development: roginolisib is the first allosteric modulator of PI3Kδ and cambritaxestat is the only autotaxin inhibitor in clinical development to treat cancer. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. iOnctura is backed by specialist institutional investors including Syncona, EIC Fund, M Ventures, Inkef Capital, VI Partners and Schroders Capital. About roginolisib Roginolisib is the first allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. The PI3K signalling pathway is one of the most commonly dysregulated pathways in cancer and the precise targeting of the PI3Kδ isoform delivers substantial anti-tumor effects with a low-toxicity profile. Clinical data have demonstrated roginolisib's excellent safety profile and sustained clinical activity in uveal melanoma (UM), a rare eye cancer with few available treatments. Randomized Phase II trials are planned to start in late 2024 in UM and other cancers, including non-small cell lung cancer and primary myelofibrosis. About the ETOP IBCSG Partners Foundation The ETOP IBCSG Partners Foundation was established through the merger of the European Thoracic Oncology Platform (ETOP) and the International Breast Cancer Study Group (IBCSG) (ETOP IBCSG Partners Foundation). The foundation, with its legal seat in Bern, Switzerland, has become a leading organization in performing international clinical research in thoracic malignancies and breast cancer. The ETOP IBCSG Partners Foundation is sponsoring and managing an increasing number of clinical trials and translational research projects in Europe and beyond. 1 AACR Volume 3, Issue 4, April 2023, Poster presentation, SITC 2022 2 Poster presentation, ESMO-IO 2023 3 Poster presentation, ESMO-IO 2023, Poster presentation EACR 2023 4 Lim, S.M. et al., Nat Commun 14, 7301 (2023) SOURCE iOnctura

The expansion to roginolisib’s clinical programme is via collaborations with ETOP IBCSG Partners Foundation and GSK. Image credit: Shutterstock/tomertu. Fresh from raising nearly $86m in financing last month, iOnctura will now start evaluating lead asset roginolisib in non-small cell lung cancer (NSCLC). The expansion to roginolisib’s clinical programme is via clinical collaboration agreements with the ETOP IBCSG Partners Foundation and GSK , iOnctura said in a 9 July press release. The Swiss biopharma iOnctura outlined plans for a Phase II study that will investigate roginolisib in combination with GSK’s PD-1 inhibitor Jemperli (dostarlimab). The combo therapy will be evaluated in NSCLC patients resistant to first-line checkpoint inhibitor therapy, with or without docetaxel. Roginolisib is an allosteric modulator of phosphoinositide 3-kinase-δ (PI3Kδ), which iOnctura says is “widely recognised as a ‘master switch’ of cancer.” Inhibition of the protein elicits an anti-tumour effect, which induces immune system activity against cancer cells.  In January this year, roginolisib received an orphan drug designation from the US Food and Drug Administration (FDA). iOnctura is basing the combination with GSK’s programmed death receptor (PD-1) on “emerging clinical and translational biomarker data,” adding that it may prevent or reverse drug resistance in NSCLC. This enhanced anti-tumour immune activity would also be without significant addition of toxicity, according to the biopharma. See Also: Dupixent “addresses current gap” in COPD biologics landscape Peltopepimut-s by ISA Pharmaceuticals for Cervical Cancer: Likelihood of Approval Roginolisib is being evaluated in a Phase I clinical trial (NCT04328844) as a monotherapy and in combination with chemotherapy in patients with advanced or metastatic cancers, including metastatic uveal melanoma . The biopharma reported positive efficacy results at the 80mg dose, with grade 1 and 2 adverse events observed in the continuous daily dosing portion of the trial for patients with solid tumors. iOnctura’s CEO Catherine Pickering said: “The successful uveal melanoma data reported so far, combined with a rich preclinical data package, support the rationale to expand our development program with potentially synergistic combinations in NSCLC.” P13K inhibitors faced a setback in recent years after the FDA’s Oncologic Drugs Advisory Committee (ODAC ) lost confidence in the safety profile of the drugs. The agency recommended that future approvals of PI3K inhibitors for haematologic malignancy indications should require randomised trial data, as per a vote in 2022. The decision was based on high levels of fatal adverse events (AEs) and toxicity observed in patients taking the drug class. Roche made a recent advancement in the space, securing FDA priority review in breast cancer for the PI3K inhibitor inavolisib as a combination therapy with fulvestrant and Pfizer ’s Ibrance (palbociclib). iOnctura raised €80m ($85.8m) in Series B financing earlier this year, helping to fund Phase II activity for roginolisib and its other candidate cambritaxestat, autotaxin inhibitor.