Emergence Therapeutics’ science is being harnessed to develop best- or first-in-class antibody drug conjugates (ADCs) for the treatment of solid tumors. Our lead product is ETx-01, an ADC against Nectin-4. Our aim is to target difficult to treat tumors with high efficacy, lower risk of side effects and the ability to avoid resistance.
Nectin-4 has been clinically validated as an ADC target by enfortumab vedotin, recently approved for the treatment of urothelial cancers by the US FDA. It is highly expressed by many different cancers and has a very limited expression in healthy tissues, especially compared to many other ADC targets.
Emergence is developing a best-in-class ADC: an improved monoclonal antibody (mAb) that avoids unwanted interactions leading to off-target toxicity; a stable linker to avoid loss of toxin in the circulation; and a new toxin, amanitin, with a novel mechanism of action against which no resistance is expected to develop and that is not sensitive to multi-drug resistance.
Amanitin is an inhibitor of RNA polymerase 2a. The gene, coding for its major subunit POLR2A, is deleted in 17p deletion tumors, leading to tumor cells with just one copy of the gene and thus producing less RNA polymerase 2a. The 17p deletion also includes TP53 gene which renders tumor cells resistant to many anti-cancer treatments and these tumors are therefore very hard to treat. But as they produce far less RNA polymerase 2a these tumors become much more sensitive to amanitin.
Amanitin has several other advantages. It is hydrophilic, improving drug product properties, it is very potent, enabling the killing of cells with low target expression and it is able to kill quiescent cells, rendering tumor stem cells vulnerable to treatment.
Emergence Therapeutics has a phased development plan to deliver on the potential of ETx-01 and its broader pipeline. Given the high unmet need in [cancers with Nectin-4 expression and 17p deletions] our objective is to seek accelerated approval through Breakthrough Therapy Designation for indications such as urothelial cancer. Additional indications would include certain breast cancers, pancreatic cancer and ovarian cancer. Longer term, we believe ETx-01 has potential as a tumor agnostic treatment for Nectin-4+/17p deletion tumors.
Beyond ETx-01 Emergence is actively exploring opportunities to develop further best- or first-in-class ADCs driven by therapeutic need.
Emergence’s in-house expertise and team is supported by collaborations with world-class partners. These include:
Licensing and collaboration agreement with SATT Sud-Est (the regional tech transfer office for the Aix-Marseille Université, CNRS and Inserm) through which the Company has been granted exclusive rights to a set of anti-Nectin-4 antibodies from Marc Lopez at the Cancer Research Center in Marseille (CRCM), France, who discovered the nectin family of proteins. SATT Sud-Est is also providing financial support to the Emergence program.
A licensing and collaboration agreement with Heidelberg Pharma Research GmbH, a subsidiary of Heidelberg Pharma AG, Ladenburg, Germany. Through this agreement Emergence has access to Heidelberg Pharma’s proprietary ATAC technology embracing innovative antibody design, amanitin-based payloads and corresponding linkers. Heidelberg Pharma Research GmbH is also a founding investor in Emergence.
An R&D collaboration with MI-mAbs, a platform for antibody research and development at the Aix-Marseille Université managed by François Romagné, co-founder and former CSO of Innate Pharma.