Mestag: Unlocking anti-tumour immune responses in solid tumour patients using a first-in-class bispecific antibody to induce Tertiary Lymphoid Structures

Mestag Therapeutics is a biotechnology company harnessing new insights into fibroblast-immune cell interactions to develop impactful treatments for patients. The company develops sophisticated first-in-class antibodies to improve the lives of people with cancer and inflammatory disease. Cancer continues to be a major public health challenge with around 20m cases/year world-wide. In the UK, 3m people live with cancer and 390,000 new patients are diagnosed every year. Although significant progress has been made in the treatment of cancer with the development of immunotherapies over the past decade, 50-70% of solid tumour patients do not respond to therapy. There is an urgent need to develop effective new therapies for solid tumour patients to increase treatment responses and improve long-term survival. Critical barriers to better outcomes include limitations on immune cells' ability to recognise the tumour ('immune cell education') and lack of access to the tumour for tumour-killing immune cells. Mestag is developing an entirely new approach, breaking away from conventional immunotherapy to address these challenges. M300 is a bispecific antibody that recruits _and_ educates new anti-tumour immune cells by inducing Tertiary Lymphoid Structures (TLS) in the tumour. TLS are known historically as aggregates of immune cells that act as immunological "advance SWAT teams" to rapidly recruit, activate, educate, and direct the immune system to locally fight infection. The importance of TLS in cancer has only recently been recognised by the scientific and clinical communities, and we now know that TLS strongly correlates with improved survival and response to therapy across solid tumour types. These striking clinical observations are replicated in over 9,000 cancer patients, indicating the remarkable therapeutic potential of induction of TLS. Mestag has established robust proof-of-concept data across multiple hard-to-treat mouse cancer models showing that its bispecific antibody approach induces TLS in the tumour, leading to potent anti-tumour efficacy. This 12-month project will enable Mestag to progress its bispecific antibody efficiently into clinical development. The project will deliver data to inform on indication and patient selection for a Phase 1 study in cancer patients, establish assays to assess drug pharmacology and safety, and identify biomarkers of response to identify patients that respond to therapy early in M300 treatment, and those that will benefit most from this therapy.