TRE-515

TRE-515 decreases deoxycytidine triphosphate (dCTP) and deoxythymidine triphosphate (dTTP) pools and increases the length of time cells spend in S phase of the cell cycle without inducing a replication stress response in B cells. Our results suggest that dCK activity is required to supply needed dNTPs and to enable rapid cell division following lymphocyte activation against autoantigens in EAE mouse models.

P1, N=85, Recruiting, Trethera | Trial completion date: Jul 2023 --> Jun 2027 | Trial primary completion date: May 2023 --> Dec 2026 | N=36 --> 85

Background: Nucleotide metabolism has been exploited for over a decade in the treatment of MS as exemplified by the success of teriflunomide and cladribine. Targeting dCK with first-in-class inhibitor TRE-515 blocks symptoms across multiple EAE mouse models by specifically limiting activated B and CD4 T cell proliferation. TRE-515 has been well tolerated in dose escalation Phase I clinical trials. TRE-515 could represent a new once a day oral treatment drug class for relapsing forms of MS with strong efficacy and predicable safety.

Taking together these results support the therapeutic potential for TRE-515 to selectively inhibit cancer cells that rely on dCK for DNA synthesis and rapid malignant proliferation. As such, TRE-515 is currently being evaluated in a phase 1 open-label, dose escalation study in solid tumors (NCT #05055609).