Dear Shareholders,
This month I want to turn your attention to the broader value-creation strategy within our portfolio, by taking a closer look at SRA737, our clinical-stage selective checkpoint kinase 1 (Chk1) inhibitor. This is a protein that cells rely on to pause and repair damaged DNA before dividing. Cancer cells, which already accumulate DNA damage at a high rate, lean particularly heavily on Chk1 to survive. Blocking this protein is designed to push damaged cancer cells past the point of repair to trigger cell death while ideally sparing healthy tissue.
Chk1 sits within the DNA Damage Response, or DDR, pathway, a mechanism that has already produced several important approved cancer medicines, such as PARP inhibitors. Despite over two decades of research and several large pharmaceutical companies attempting to develop Chk1 inhibitors, there remains no approved medicine in this target class today. Earlier candidates, including AstraZeneca’s AZD7762, demonstrated early clinical activity but were ultimately constrained by dose-limiting toxicities.[1],[2] However, there has been recent progress in overcoming the earlier constraints of this drug class, including Sumitomo Pharma’s Chk1 inhibitor, SMP-3124LP, demonstrating antitumour activity (partial response and stable disease rates of 9 and 39% respectively) with a manageable safety profile.[3] With this in mind we believe Chk1 is a validated, first-in-class opportunity for any company able to develop a better-tolerated molecule.
In Phase 1/2 clinical studies, Sareum’s SRA737 asset demonstrated good tolerability as a monotherapy and showed promising activity in combination with low-dose gemcitabine (LDG) in anogenital cancers, an area of significant unmet medical need. We believe that Chk1 inhibitors will ultimately be used in combination with chemotherapeutic or targeted anti-cancer agents, and the clinical safety profile of SRA737 as a monotherapy confers a potential advantage over other developmental Chk1 inhibitors in combination therapies. For example, it’s worth noting how SRA737 compares with the Sumitomo programme referenced above. Sumitomo’s Chk1 inhibitor is delivered via an intravenous liposomal formulation, whereas SRA737 is an oral, selective small-molecule Chk1 inhibitor which demonstrated partial response and stable disease rates of 11% and 63% in a LDG combination trial.
Meanwhile, several research groups continue to investigate the potential combination strategies for SRA737 and other Chk1 inhibitors. We noted with particular interest recent research published by the Gabrielli group demonstrating that combining SRA737 with low-dose hydroxyurea (LDHU) showed highly synergistic efficacy in disease models of melanoma and ovarian cancer, with upregulation of a pro-inflammatory microenvironment, transforming tumours from their “cold” immunosuppressive state to a “hot” inflamed state, enhancing the potential of the immune system to clear such tumours.[4]
We hold the licence for SRA737 on significantly improved economic terms, securing 63.5% of all future revenues compared with 27.5% under the previous agreement, at no cost to the Company. With SRA737’s broad potential applicability, we have also maintained an active Investigational New Drug application with the FDA to conduct a Phase 1 trial in patients with acute myeloid leukaemia and myelodysplastic syndromes, and we retain sufficient stock of SRA737 capsules to conduct such a trial without further manufacturing investment. Additionally, we have a robust patent strategy to maintain and extend the IP protection around SRA737 and its use in treating cancer.
SRA737 illustrates how we think about portfolio construction more broadly. While SDC-1801 remains our primary focus as we work towards completion of its Phase 2-enabling regulatory package, SRA737 gives us a second and capital-efficient route to further value creation. We continue to explore the best route to realise this value, whether through re-licensing, partnering or internal development, and will update shareholders as these discussions progress.
As always, we are grateful for your continued support and interest in Sareum, and we look forward to updating you further as our business development activities progress across the portfolio.
Stephen Parker,
Executive Chairman,
Sareum Holdings plc
[1] Functions and inhibitors of CHK1 in cancer therapy. https://www.sciencedirect.com/science/article/pii/S2590098624000101
[2] Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors. https://pmc.ncbi.nlm.nih.gov/articles/PMC4486055/
[3] Sumitomo Pharma America Presents First Clinical Data for SMP-3124LP, an Investigational PEGylated Liposome CHK1 Inhibitor, at ASCO 2026. https://news.us.sumitomo-pharma.com/press-release-details/2026/Sumitomo-Pharma-America-Presents-First-Clinical-Data-for-SMP-3124LP-an-Investigational-PEGylated-Liposome-CHK1-Inhibitor-at-ASCO-2026/default.aspx
[4] Zeng, Z., Gandini, A., Bhatt, R. et al. Using targeted therapy to promote a pro-inflammatory tumour microenvironment and anti-tumour immune response in high grade serous ovarian cancer. Br J Cancer 134, 1830–1840 (2026). https://doi.org/10.1038/s41416-026-03416-y