University Hospitals Cleveland Medical Center

OXFORD, UK and CLEVELAND, Ohio, US, 24th September 2024 – The Oxford-Harrington Rare Disease Centre (‘OHC’), a partnership between the University of Oxford, UK and Harrington Discovery Institute at University Hospitals, Cleveland, Ohio, aimed at delivering cutting-edge rare disease breakthroughs, is pleased to announce it is hosting its bi-annual Symposium today through 26th September 2024, at Trinity College, University of Oxford. The event will bring together leaders from academia, biotech, pharma, venture capital, philanthropy and patient groups to connect, engage and update the diverse and growing rare disease community. The Symposium explores how cutting-edge research, innovative treatment strategies, and collaboration is driving the development of effective therapies for rare diseases. Symposium 2024 Highlights: The three-day in-person event begins with Opening Remarks from Professor Matthew Wood, Director and Chief Scientific Officer of the OHC, and Sir John Bell, President, Ellison Institute of Technology, and Chair of the OHC Advisory CouncilAn Opening Session features Baroness Nicola Blackwood, Chair, Genomics England, Member of the House of Lords, and the OHC’s Advisory Council Further notable speakers will include Jonathan S. Stamler, MD, President and co-Founder, Harrington Discovery Institute and Member of the OHC Steering CommitteeJulia Vitarello, Founder & CEO, Mila’s Miracle FoundationProfessor Fyodor Urnov, Professor of Molecular & Cell Biology, University of California Berkeley Other sessions examine critical topics in rare diseases, such as therapeutic genomics, drug development exemplars, lifelong therapies for neuromuscular diseases, and paediatric cancer. These sessions will showcase the latest research and innovations shaping the future of rare disease therapeutics. The Symposium programme, available here, also offers updates on the OHC’s Therapeutics Accelerator, launched on October 3, 2023. This groundbreaking initiative, backed by up to £200 million in funding, operates under a unique non-profit/for-profit model through a partnership with Harrington Discovery Institute, University Hospitals of Cleveland, University of Oxford, and Oxford Science Enterprises. A highlight of the Accelerator at this year’s Symposium is AlveoGene, an innovative company pioneering inhaled gene therapy for rare respiratory diseases. This session will feature David Hipkiss (Executive Chair). Matthew Wood, Director and Chief Scientific Officer of the OHC, commented: “This year’s Oxford-Harrington Rare Disease Symposium is a unique opportunity to bring the international rare disease community together to recognise scientific progress and innovation and foster collaboration among leaders in the field. I am delighted to welcome global leaders from academia, industry, government, and patient advocacy to come together with a shared commitment to translating science into tangible outcomes for rare disease patients and their families.” *** Notes to Editors About Rare DiseasesMore than 400 million people worldwide are living with a rare disease, and approximately 50 percent are children. There are about 7,000 known rare diseases, with new diseases being discovered every day. A rare disease affects one in 10 Americans, or 10 percent of the US population. Similarly, Europe has approximately 30 million people who suffer from a rare disease. The majority of all rare diseases are genetic in origin, which means they are present throughout a person’s life. Only five percent of rare diseases have a treatment approved by the US Food and Drug Administration (FDA) and similar estimates have been made for treatments approved by the European Medicine Agency (EMA). Therefore, someone with a rare disease today faces a lifelong, often life-threatening, condition with little hope for a cure, or even an effective treatment option. About Oxford-Harrington Rare Disease CentreThe Oxford-Harrington Rare Disease Centre (OHC) is a partnership between the University of Oxford, UK and Harrington Discovery Institute at University Hospitals, in Cleveland, Ohio, US. The OHC combines world-leading strengths in research and therapeutics development from across these organizations to set the science and innovation agenda and drive cutting-edge rare disease breakthroughs to address the unmet need in rare diseases across the globe to deliver major clinical impact for patients. For more information, visit: OxfordHarrington.org | LinkedIn | X About the University of OxfordThe University of Oxford is rated the best in the world for medicine and life sciences, and it is home to the UK’s top-ranked medical school. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery. The University of Oxford’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. For more information, visit: www.ox.ac.uk About Harrington Discovery InstituteThe Harrington Discovery Institute at University Hospitals in Cleveland, Ohio – part of The Harrington Project for Discovery & Development – is a translational accelerator that advances promising discoveries from academic labs into the clinic for the benefit of patients and society. The institute was created in 2012 with a $50 million founding gift from the Harrington family and is a prime example of the commitment they share with University Hospitals to a Vision for a ‘Better World’. For more information, visit: HarringtonDiscovery.org| LinkedIn | X Media contacts: UK/ EU – MEDiSTRAVA Sylvie Berrebi / Mark SwallowOHC@medistrava.com US – For University HospitalsAnsley Kelmansley.kelm@UHhospitals.org

BOSTON--( BUSINESS WIRE )--Scorpion Therapeutics, Inc. (“Scorpion”), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision oncology, today presented initial, first-in-human clinical results from its Phase 1/2 study of STX-478 in advanced solid tumor patients in a Proffered Paper late-breaking session at the European Society for Medical Oncology (“ESMO”) Congress 2024 in Barcelona, Spain. Initial Phase 1 monotherapy data for STX-478, an oral, once-daily, mutant-selective, allosteric PI3Kα inhibitor, demonstrated potentially best-in-class PI3Kα inhibition, with anti-tumor activity observed in multiple cancer types, including HR+/HER2- breast cancer (BC), gynecological tumors, and other solid tumors. STX-478 was well-tolerated, including in pre-diabetic, diabetic and heavily pre-treated patients and showed no significant wild-type-mediated toxicities. “We are pleased to report the initial Phase 1/2 trial results of STX-478, which was designed as the first PI3Kα inhibitor to fully maximize the potential of pathway inhibition in patients with solid tumors and is the first program emerging from our next-generation precision oncology discovery engine,” said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion. “STX-478 demonstrates potent and potentially best-in-class PI3Kα pathway inhibition as established by our early, differentiated signals of monotherapy efficacy, which exceed benchmarks of other pathway inhibitors. We also are encouraged by early safety data that demonstrates minimal evidence of wild-type PI3Kα-mediated toxicities, with no patients discontinuing STX-478 due to treatment-related adverse events. Together, these results suggest that our highly-selective mutant PI3Kα inhibitor could overcome the limitations of currently available pathway inhibitors and, consequently, meaningfully improve clinical outcomes for patients with PI3Kα kinase or helical domain-mutated solid tumors. We look forward to continuing to progress our clinical-stage and discovery pipeline as we work to broaden the reach and impact of precision oncology for patients with high unmet medical need.” “Approved and investigational non-selective PI3Kα inhibitors, as well as approved AKT inhibitors, have shown clinical benefit in HR+/HER2- breast cancer in Phase 3 studies. However, their therapeutic benefit is limited by PI3Kα pathway inhibition in normal tissues, resulting in dose-limiting toxicities, including hyperglycemia, rash and diarrhea,” said Alberto J. Montero, M.D., affiliated with University Hospitals Cleveland, and trial investigator. “By selectively targeting mutant PI3Kα, one of the most prevalent oncogenes in cancer, STX-478 has the potential to improve clinical outcomes and quality of life for patients during treatment. In the trial, STX-478 achieves exposures capable of driving several-fold deeper target inhibition than other PI3Kα inhibitors, while avoiding their toxicities, even with the majority of patients having prediabetes or diabetes. I am excited about the early results in patients with breast cancer and other solid tumors and look forward to further clinical development.” Initial Data from the Phase 1/2 Study of STX-478 in Advanced Solid Tumors In the Proffered Paper presented at ESMO, 61 patients with both kinase and helical domain PIK3CA mutations were treated with STX-478 at doses ranging from 20mg to 160mg daily, as of the data cutoff on June 21, 2024. Of the enrolled patients, 29 patients had HR+/HER2- BC and 32 patients had other solid tumors. Additionally, 54% of patients were pre-diabetic or diabetic, and 41% of BC patients had a prior PI3Kα pathway inhibitor. 97% of BC patients had previously received a CDK4/6 inhibitor. Enrolled patients were heavily pre-treated with a median of three prior lines of therapy (ranging from 1-7). Pharmacokinetic and Selectivity Profile Preliminary pharmacokinetic analysis supports once-daily dosing of STX-478, with dose proportional and linear STX-478 plasma exposure and an estimated half-life of approximately 60 hours. At doses ≥ 40mg QD, STX-478 exceeded the average exposures needed for in vivo efficacy in mouse models and achieved target coverage several fold higher than other approved or investigational PI3Kα inhibitors. STX-478 reached a maximum tolerated dose (MTD) of 100mg daily. Preliminary Safety Data STX-478 was well-tolerated in a high-risk population, which included diabetics, pre-diabetics and patients intolerant to other PI3Kα pathway inhibitors, populations excluded from other PI3Kα studies. Most treatment-related adverse events (TRAEs) were mild-to-moderate and transient; TRAEs of ≥ 15% included: fatigue (30%), hyperglycemia (23%), nausea (20%) and diarrhea (15%). No Grade ≥ 3 PI3Kα WT toxicity adverse events (hyperglycemia, diarrhea and rash) were observed, and minimal changes in fasting glucose were observed at any STX-478 dose level. No patients discontinued STX-478 due to a TRAE, and two dose-limiting toxicities observed at 160mg rapidly resolved after a brief dose interruption. Initial Clinical Activity Data As of the data cutoff in 43 evaluable patients, the confirmed/unconfirmed overall response rate (ORR) was 23% (5/22) in HR+/HER2- metastatic breast cancer; 21% (9/43) in all tumor types; and 44% (4/9) in gynecologic cancers, which compares favorably to approved PI3Kα pathway inhibitors (monotherapy ORR 4 – 6%). All responses were confirmed following the data cutoff. The disease control rate across tumors was 67%. Tumor reductions were seen in 72% of all patients as a monotherapy agent across all dose levels. Multiple responses were seen in both PI3K α kinase and helical domain mutant tumors at multiple dose levels, and many responses were sustained and deepened over several months of therapy. Mutant PIK3CA circulating tumor DNA levels markedly decreased on therapy in 86% of patients (19/22 evaluable patients). The presentation will be available here on Scorpion’s website following the conclusion of the session. “Scorpion is dedicated to bringing highly-selective small molecules to cancer patients as quickly as possible, and the presentation of these data is a testament to the team’s exceptional execution and the productivity of our fully-integrated discovery organization,” said Mark Chao, M.D., Ph.D., Chief Medical Officer of Scorpion. “These exciting data bolster our confidence in the profile of STX-478 and in the continued advancement of the trial as we actively enroll patients into ongoing multiple expansion cohorts across a range of solid tumors and in combinations with active standard of care agents including fulvestrant and CDK4/6 inhibitors in HR+/HER2- breast cancer and lay the groundwork for the rapid advancement of this novel treatment. We would like to thank the patients, caregivers and investigators for sharing our commitment to advancing next-generation cancer treatments, and we look forward to providing updates from this study at future medical meetings.” About STX-478 STX-478 was designed to improve outcomes in patients harboring PI3Kα mutations, one of the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. In preclinical models, STX-478 demonstrated robust activity across a range of both kinase and helical domain PI3Kα mutations while sparing wild-type PI3Kα activity in normal tissues; previous generations of non-selective PI3Kα inhibitors have limited patient benefit due to these on-target toxicities. Scorpion’s Phase 1/2 clinical trial is a multi-center, global, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer and other solid tumors driven by PI3Kα mutations. The program has rapidly advanced into multiple expansion cohorts across a range of solid tumors and in breast cancer as monotherapy and in combinations with fulvestrant and CDK4/6 inhibitors. To learn more about the first-in-human trial of STX-478, please visit this page . About Scorpion Therapeutics Scorpion is a pioneering clinical-stage oncology company redefining the frontier of precision medicine to deliver optimized and transformational therapies for larger populations of patients with cancer. Scorpion has built a proprietary and fully-integrated platform of the most advanced technologies across cancer biology, medicinal chemistry, and data sciences, with the goal of consistently and rapidly creating exquisitely selective small molecule compounds against an unprecedented spectrum of targets. Scorpion aims to leverage its platform to advance a broad pipeline of wholly-owned, optimized compounds across three target categories: best-in-class molecules targeting validated oncogene targets; first-in-class molecules for previously undruggable targets; and first-in-class molecules for novel cancer targets. For more information, visit www.scorpiontx.com .

Diabetes and insulin management software company Glytec and pharmaceutical firm Roche are teaming up to allow the use of Glytec's software in connection with Roche's point-of-care smart-device hospital blood glucose system cobas pulse in the U.S. and global markets. According to Roche, cobas pulse's strip architecture provides lab-like results and minimizes the need to repeat tests. The system can be used on all patient populations, including neonates and intensive care patients. Glytec's FDA-cleared insulin-dosing decision support software Glucommander is used for inpatient diabetes treatment and to help healthcare providers maximize glycemic management strategies and enhance outcomes. The collaboration coincides with Glytec's strategy to empower synergistic diabetes and insulin management. By capitalizing on Roche's global presence and Glytec's stable track record, the joint venture aims to elevate patient safety, strengthen the cost-effectiveness of care and improve outcomes. "Diabetes knows no borders, profoundly impacting hospital diabetes management and patient outcomes worldwide," Robby Booth, cofounder and chief strategy officer at Glytec, said in a statement. "We are proud of our expanded collaboration with Roche, which reaffirms our commitment to addressing this critical healthcare challenge for patients, providers and payers and positively impacting lives worldwide." THE LARGER TREND In August, Glytec announced support for CMS's new mandatory reporting requirements aimed at improving hyperglycemia and hypoglycemia measures. The move advances diabetes excellence across the U.S., particularly benefiting rural and underserved communities, and enhances broader value-based care initiatives. In June, the company announced a strategic partnership with Major Health Partners (MHP), a community-based hospital in Shelbyville, Indiana, that integrated Glytec’s FDA-cleared Glucommander software. MHP aims to use the software to standardize insulin titration and reduce risks of severe hypoglycemia. In May, Glytec announced a partnership with the Cleveland Clinic to deliver its insulin management software platform to UH Cleveland Medical Center. The software platform leverages evidence-based algorithms and real-time data analysis to personalize dosing for all patients requiring insulin. In 2021, the insulin management software company received $21 million in funding from Silicon Valley Bank, Savitr Capital and other private investors. It collected $9 million in debt financing from SVB and $12 million in equity investments led by Savitr positions.