Public Funding for Kinomica Limited

Decades of intensive research has produced a wealth of anticancer treatments. A problem for the success of these therapies is that not all patients will respond to treatments in the same way, so some may respond well to a treatment while others respond poorly to that same treatment. It is difficult therefore to know, or predict, which patients will be responders or non-responders to the growing number of available drugs. This project addresses this clinical, societal and economic challenge. We propose the development of a new type of diagnostic test based on predictive protein activity signatures, that will be able to distinguish how well a patient is likely to respond to different anticancer drugs. While several competing technologies in the field of precision medicine diagnostics now exist, Kinomica's solution has a competitive advantage because it is based on measuring the activity, rather than just mutations or abundance levels, of proteins that drive cancer growth and are the targets of drugs designed to block cancer growth. The project builds from previous work, in part funded by Innovate UK, where we demonstrated that our technology predicted responses to a treatment (midostaurin plus chemotherapy) for an aggressive form of leukaemia, with much greater accuracy than when using the currently approved diagnostic tests (based on gene mutation analysis). Successful completion of the project will provide a test that can select the best drug for each leukaemia patient from the growing number of available treatments, thus improving response rates, survival times and quality of life. Furthermore, this work will lead to new and improved methods, inventions and improved diagnostics to help clinicians treat their cancer patients effectively. The outputs will be made public in high-impact publications and presentations in conferences. Importantly, the project will deliver a novel diagnostic technology that could be applied to help more effectively treat other cancers beyond leukaemia. This project will change our R&D activities by unlocking additional private funding, and opens the prospect of creating a centre of excellence in precision medicine diagnostics in the North West of England, with the positive consequent implications for economic development in the area.

Decades of intensive research has produced a wealth of anticancer treatments. A problem for the success of these therapies is that not all patients will respond to treatments in the same way, so some may respond well to a treatment while others respond poorly to that same treatment. It is difficult therefore to know, or predict, which patients will be responders or non-responders to the growing number of available drugs. This project addresses this clinical, societal and economic challenge. We propose the development of a new type of diagnostic test based on predictive protein activity signatures, that will be able to distinguish how well a patient is likely to respond to different anticancer drugs. While several competing technologies in the field of precision medicine diagnostics now exist, Kinomica's solution has a competitive advantage because it is based on measuring the activity, rather than just mutations or abundance levels, of proteins that drive cancer growth and are the targets of drugs designed to block cancer growth. The project builds from previous work, in part funded by Innovate UK, where we demonstrated that our technology predicted responses to a treatment (midostaurin plus chemotherapy) for an aggressive form of leukaemia, with much greater accuracy than when using the currently approved diagnostic tests (based on gene mutation analysis). Successful completion of the project will provide a test that can select the best drug for each leukaemia patient from the growing number of available treatments, thus improving response rates, survival times and quality of life. Furthermore, this work will lead to new and improved methods, inventions and improved diagnostics to help clinicians treat their cancer patients effectively. The outputs will be made public in high-impact publications and presentations in conferences. Importantly, the project will deliver a novel diagnostic technology that could be applied to help more effectively treat other cancers beyond leukaemia. This project will change our R&D activities by unlocking additional private funding, and opens the prospect of creating a centre of excellence in precision medicine diagnostics in the North West of England, with the positive consequent implications for economic development in the area.

Primary liver cancer is the fourth most prevalent cancer globally and the third highest cause of cancer deaths. Rising incidence coupled with an appalling 5-year survival rate of less than 15% is forecast to result in up to 1 million deaths in 2030\. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer cases, with around 5,900 new cases diagnosed annually in the UK. Despite the use of very expensive state-of-the-art technology for diagnosis and treatment, the best-available current treatments provide only marginal benefits for approximately 70% of HCC patients. A major underlying issue is the almost complete absence of biomarkers (a means of measuring biological conditions) to effectively match systemic treatments to HCC patients. Our project combines the clinical expertise of King's College Hospital and King's College London (KCH & KCL) with the innovative diagnostic capabilities of Kinomica Ltd. KCH & KCL are front-line liver cancer oncologists, transplant surgeons and pathologists witnessing first-hand how the clinical pathway underserves their patients. Their need has inspired our collaborative project to address this market failure. Kinomica's flagship innovation is the KScan(R) platform, underpinned by proprietary machine learning algorithms, that enables more accurate biomarker diagnostics. This has been demonstrated as being able to outperform state-of-the-art biomarker diagnostics for targeted therapy treatment for acute myeloid leukemia (AML). The company is scaling rapidly in preparation for rolling out our transformative diagnostic, and now seeks to expand into new indications where there is crucial need. During this project, together with KCH & KCL, Kinomica will apply KScan(R) to build on the novel liver cancer biomarkers we have already identified through preliminary investigations. We intend to emulate our AML successes to fully develop and validate clinically effective biomarker panels to guide systemic HCC therapies, based on patient outcomes, and commence prototyping a KScan(R) diagnostic steered by indicative health economics, and clinical and patient pathway assessments. This project will cover all necessary research and development prior to clinical trials, which will be conducted post-project. After 2025, we intend to commence deploying an effective diagnostic that improves therapy response by 15%, extending and improving quality of life of tens of thousands of HCC patients, and potentially avoiding over £1Bn that is spent on ineffective treatments globally. The innovation and commitment of the partners will thus be a valuable contribution to UK science and healthcare.

"Acute myeloid leukaemia (AML) is an aggressive form of blood cancer, where only about 20% of patients are expected to survive for 5 or more years after diagnosis. A new drug called midostaurin can triple survival times for some patients and is now available on the NHS. However, only a subgroup of AML patients (~30%) are eligible to receive this treatment and approximately 50% of those will experience no benefit; therefore, only about 15% of AML patients overall actually benefit from treatment. Consequently, many patients are exposed to unnecessary side-effects, are denied the opportunity to be recruited on trials for drugs that may be effective, and the NHS are subjected to unnecessary costs (\>£23M/year) treating patients that fail to benefit. The diagnostic test used to determine patient eligibility to receive midostaurin is called LeukoStrat(r), which assesses whether an AML patient's cancer cells have mutations in a gene called FLT3\. Patients who are positive for this ""biomarker"" will receive midostaurin. Early clinical trials and a recent pre-clinical study by Kinomica's Founders showed that 42-65% of patients _without_ the FLT3 mutation biomarker (representing 70% of all AML patients) responded well to midostaurin, so there is likely a significant number of patients currently classified as ineligible who could benefit from treatment. Midostaurin is currently in the very advanced stages of clinical trials for use in patients without the FLT3 mutation biomarker. Thus the importance of identifying those who will benefit from treatment becomes even greater, as the cost to the NHS to treat patients who will not benefit could triple. The variable response rates for midostaurin treatment in AML (with and without mutated FLT3), suggest that the current FLT3 mutation biomarker and medical test to detect this marker (LeukoStrat(r)) are severely limited. Kinomica's Founders have developed a new and much more accurate way to predict whether an AML patient will respond to midostaurin. Kinomica's approach involves measuring the activity of an important group of proteins called kinases, within a patient's cancer cells. This readout can then better predict whether midostaurin will destroy those cells. Funding is sought so that Kinomica can develop the technology into a clinical test. The realisation that kinase activities are better predictors of therapeutic response than genetic alterations will likely have far wider implications for the development of personalised therapies across many cancer types."