IgE antibodies exert strong immunostimulatory effects and their anti-tumour effectiveness is currently being assessed in clinical trials. The high affinity of IgE for FcεRI may result in the binding of exogenously delivered antibody to effector cells prior to antigen engagement, potentially leading to IgE being presented multivalently to cancer cells. With the presumed higher avidity of antigen binding it is unclear whether increasing monovalent affinity of IgE improves anti-tumour functionality. To address this, we affinity-matured an anti-HER2 IgE, generating 12 clones with increased affinity for HER2. These clones were more potent than the parental antibody in inducing mast cell degranulation, with the most potent, EPS 232, achieving enhanced antibody-dependent cytotoxicity and phagocytosis of HER2-expressing cancer cells. EPS 232 delivered superior tumour growth inhibition in vivo, including in models expressing ultra-low levels of HER2, and it promoted greater infiltration of T cells and macrophages into tumours. These findings suggest that for therapeutic IgE, increasing antigen-binding affinity can lead to functional enhancements.
Category: In the News
Epsilogen Ltd was pleased to host representatives from the US Advanced Research Projects Agency for Health (ARPA-H) at its facilities. The team welcomed Amy Lin, Director of the Division of International Affairs at ARPA-H, and Taeko Noah, PhD, Technical SETA, for a visit that included discussions on ongoing collaboration and a tour of the company’s operations.
Since 2024, ARPA-H has been working with TigaTx, Inc., a wholly owned subsidiary of Epsilogen, to advance the development of TigaTx’s engineered monomeric IgA neutrophil engagers for cancer, alongside engineered dimeric IgA therapeutics targeting infectious diseases.
NEW YORK – Epsilogen on Monday said that by acquiring TigaTx, it has gained new antibodydesign capabilities that can boost its early-stage precision oncology pipeline.
Boston-based TigaTx has become a wholly owned subsidiary of Epsilogen, which is headquarteredin London. Concurrently with the acquisition, Sonia Gulati, a principal at Global BioAccess Fund,has joined Epsilogen’s board of directors. The companies did not disclose the financial terms of thetransaction.
In December 2024, Epsilogen launched a Phase Ib trial of its investigational therapeutic antibodyMOv18 IgE in patients with FRα-expressing, platinum-resistant ovarian cancer whose disease hasprogressed after no more than four lines of prior therapy. MOv18 IgE targets FRα, an antigen foundon more than 70 percent of ovarian cancers. The treatment comprises a portion of the stem regionof an IgG antibody appended to an intact IgE antibody, combining the functions of both. IgE haspotent immune effector functions, which evolved to defend against parasites. It uses differentmechanisms to recruit immune cells than IgG, and an immunotherapy that exploits its functions,may be more effective against immunologically cold tumors.
In acquiring TigaTx, Epsilogen will add the firm’s IgA expertise and technology to its capabilities,enabling the development of new antibody combinations with enhanced potency. “Combining thecapabilities of Epsilogen with those of TigaTx gives us the ability to choose the most relevantisotype for a given cancer, whether [in] a cold tumor environment [where] we want to drive multipleimmune effector cells into or leverage neutrophils,” Epsilogen CEO Tim Wilson said in a statement.”The transaction also facilitates the combination of different isotype functions into a single antibodymolecule.”
The combined company will continue to advance the MOv18 IgE program and pursueinvestigational new drug application-enabling studies of EPS 401, TigaTx’s anti-EGFR IgA antibody.TigaTx researchers hope to generate clinical proof-of-concept data on the drug, which it believeshas the potential to be a therapeutic option for patients who are resistant to or intolerant of anti-EGFR therapies.
In December 2024, TigaTx received up to $35.5 million in funding from the Advanced ResearchProjects Agency for Health (ARPA-H) and a $2 million small business innovation research (SBIR)grant from the National Cancer Institute.
Cancer Research Horizons (CRH) is harnessing the skills, expertise, and research network of its parent organization to speed-up the discovery and development of transformative oncology drugs, improve patient outcomes, and advance assets for biopharma partners.
Epsilogen and Lonza have successfully completed large-scale GMP manufacturing of MOv18 IgE, to treat platinum-resistant ovarian cancer (PROC) patients.
Lu Rahman selects some of the year’s interesting and noteworthy advances in cancer research drug discovery and development.
As always, a year within cancer drug discovery and development brings with it significant breakthroughs, and 2023 has been no exception.
Parasites, allergy and innovation – the journey to get the first IgE anti-cancer drug into a human was certainly not easy. Here we follow Sophia Karagiannis and James Spicer on an immunological adventure as they work with our Centre for Drug Discovery on this potentially ground-breaking new class of drug.
PwC’s UK Life Sciences Future50 celebrates a selection of companies that illustrate the world-class science and innovation by life sciences businesses in the UK, which are aiming to solve some of the most important challenges in scientific research and human healthcare.
Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptoralpha: a phase I trial
Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanomaassociated antigen chondroitin sulfate proteoglycan 4