Yellowstone Biosciences launches with £16.5 million to pioneer soluble bispecific TCR-based therapies for cancer

New oncology company created to unlock a novel class of therapeutics targeting human leukocyte antigen (HLA) Class II expression in a range of common cancers • Spun out of the University of Oxford from the pioneering work of Professor Paresh Vyas, initially starting in acute myeloid leukaemia (AML) with broader pipeline potential across a range of cancers • £16.5 million in Series A funding from lead investor Syncona to progress operational build, lead programme and potential pipeline expansion. Oxford, UK, 20 June 2024 – Yellowstone Biosciences (“Yellowstone” or “the Company”), a pioneer of soluble bispecific T-cell receptor (TCR)-based therapies for human leukocyte antigen (HLA) Class II (HLA-II) targets in oncology, launches today to unlock a new class of therapeutically targetable, frequently expressed antigens with potential to significantly transform patient lives. Syncona Limited (“Syncona”) committed £16.5 million to fund the Company in progressing its operational build, lead programme in acute myeloid leukaemia (AML), and exploration into expanding its pipeline. Spun out of the University of Oxford with the support of Oxford University Innovation (OUI), Yellowstone is built around the pioneering research of Professor Paresh Vyas, a world-renowned scientific academic, key opinion leader and practising clinician with a specialist focus on AML. Over 20 years, Prof. Vyas’ laboratory has collected a proprietary biobank of over 10,000 samples from over 3,000 AML patients, including a rare cohort of patients cured by allogeneic blood cell transplantation. From this cohort a novel set of frequently expressed peptide antigens presented by HLA Class II were identified, which could unlock a new class of highly selective cancer therapeutics. With privileged access to this biobank, Yellowstone has been formed to develop soluble bispecific TCRbased therapeutics targeting HLA Class II presented peptides on the surface of cancer cells in a number of cancers with high unmet need. By targeting peptides presented by HLA-II molecules, the Company’s bispecific T-cell engagers have the potential to selectively kill target tumour cells, whilst sparing healthy cells. The Company will focus initially on its lead programme in AML, which accounts for 62% of all leukaemia deaths1 and where there is no universally agreed standard of care for the majority of patients. Beyond AML, Yellowstone’s technology also has the potential to extend life and change the treatment landscape in other common solid tumours that express HLA-II, including ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, prostate cancer, breast cancer, renal cancer and melanoma. Yellowstone will be led by a world-class management team, including Prof. Vyas, as Co-founder and Chief Scientific Officer, and Julian Hirst, who joins as Co-founder and Chief Financial Officer, bringing with him 20 years’ experience in biotechnology and investment banking, including senior finance roles at Immunocore and MiroBio. Neil Johnston also joins as Executive Chair, having spent 17 years at Novartis, most recently as Global Head of Business Development and Licensing. The Company will be guided by Syncona, a leading FTSE 250 life sciences investor, who has supported company launch and will continue to shape Yellowstone’s operational build. Chris Hollowood, CEO of Syncona, and Gonzalo Garcia, 1 Shallis R.M. et al (2019) ‘Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges’, Blood Reviews, 36, pages 70-87. Available at https://doi.org/10.1016/j.blre.2019.04.005 Investment Partner at Syncona, will hold Board positions at Yellowstone as part of the lead investor’s ongoing involvement. Professor Paresh Vyas, Co-founder and Chief Scientific Officer of Yellowstone, said: “Frequently expressed antigens that can be targeted therapeutically are notoriously difficult to find but, through two decades of research, we have identified a new class of targets that have potential to treat cancer and extend patient’s lives. We believe that our technology has the potential to selectively kill tumour cells, whilst sparing healthy cells, in a range of cancers. The strategy that we have built, alongside Syncona, will initially focus on developing highly selective TCR-based therapies for AML, where we have formidable experience and data. Beyond that, we are committed to broadening our pipeline to other cancer settings to maximise Yellowstone’s potential.” Gonzalo Garcia, Investment Partner at Syncona and Non-executive Director at Yellowstone, commented: “Yellowstone is the latest company formed from Syncona’s model of creating and building businesses based on exceptional science and world-class founders. The work Prof. Vyas has undertaken in this field is truly remarkable. Although difficult to identify, tumour-selective, frequently expressed antigens are particularly strong cancer targets as they allow development and manufacturing of therapies that can treat large numbers of patients. We believe that Syncona can build a globally leading UK company around this novel discovery that has significant patient and commercial potential.” Yellowstone’s academic founders received support during the spin out from OUI’s Dr. Susan Campbell and Dr. Benedicte Menn. As part of their ongoing involvement, OUI will hold a board observer position at the company. Dr Benedicte Menn, Senior Investment Manager, Oxford University Innovation, said: "With ambition to become a world class UK company, Yellowstone is our latest spinout from the University of Oxford. The company has potential to treat and extend the life of patients with different forms of cancer, starting with acute myeloid leukaemia. We’re delighted that Yellowstone and Syncona are partnering on thislaunch and look forward to tracking the progress of the pipeline.”