In 2017, Domain Therapeutics has incorporated SeaGull with Guido Serini, Enrico Giraudo and Luca Tamagnone, three academic researchers from IRCC (University of Turin). The asset-centric company is aiming at leading to the clinic a mutated version of the Semaphorin 3A (SGL 10060) able to reprogram the tumor microenvironment (TME). The TME is known to promote the tumorigenesis, to ease the dissemination of metastasis and offer an immunosuppressive context. In multiple in vivo models, SGL 10060 was shown to inhibit the release of metastasis, to potentiate the immune response and normalize the tumor vascularization. Backed to a strong IP, the program is now in preclinical development.
The Semaphorin3A/PlexinA4 axis has been shown to possess antitumoral properties. Sema3a is a natural ligand of PlexinA4 and Neuropilin 1, two receptors inducing respectively a tumor suppressor- and a protumorigenic-activity. SGL10060 is a stable, easily purifiable and parenterally deliverable Sema3A mutant. It is capable of selectively binding PlexinA4 with high affinity and effectively triggering its downstream pathway leading to tumor inhibition. This effect is mediated by the normalization of the tumor microenvironment and the enhancement of antitumor immune response.
The program is preclinical stage.