Cereno Scientific has published the first peer-reviewed paper describing its investigational histone deacetylase inhibitor CS014, reporting antithrombotic efficacy without increased bleeding risk in preclinical models.

The manuscript appears in the Journal of Thrombosis and Haemostasis and provides the first detailed public description of CS014, including its chemical structure, proposed mechanism of action and nonclinical pharmacology. According to the authors, the data show that CS014 produces strong antithrombotic effects across multiple vascular models while maintaining normal haemostasis, a profile that could differentiate the compound from existing antithrombotic approaches.

The study, titled Novel histone deacetylase inhibitor, CS014, attenuates in vivo thrombosis while maintaining hemostasis, characterises CS014 as a new chemical entity designed to build on the known epigenetic effects of histone deacetylase inhibition. The compound was engineered as an alternative to valproic acid, with the aim of reducing hepatotoxicity risk while preserving the therapeutic mechanism associated with HDAC inhibition.

In a series of in vivo experiments, CS014 demonstrated antithrombotic activity in small artery, large artery and large vein models. The authors report that these effects were achieved at doses that did not prolong bleeding time or impair coagulation. In addition, the compound was shown to increase tissue plasminogen activator mRNA expression, supporting a mechanistic link between HDAC inhibition and thrombus regulation.

The paper also reports metabolic data comparing CS014 with valproic acid. CS014 produced substantially lower levels of the hepatotoxic 4-ene metabolite in both in vitro and in vivo systems, which the authors suggest may translate into an improved safety profile.

Rahul Agrawal, cmo and head of r&d at Cereno Scientific, said: “CS014 was designed to retain the epigenetic properties of HDAC inhibition of VPA while aiming to improve its safety and metabolic profile.” He added: “This publication describes how the data supports the rationale behind that design, clearly demonstrating potent antithrombotic activity without increased bleeding risk.”

Agrawal said the findings support further exploration of CS014 in diseases where thrombosis, vascular remodelling and fibrosis intersect, including cardiopulmonary indications.

The publication follows the recent completion of a Phase 1 clinical study of CS014. Cereno Scientific has previously reported that the compound was well tolerated at and above exposure levels predicted from nonclinical data to support effects on pulmonary vascular remodelling and fibrosis. The company says these results support continued clinical development.

Sten Sörensen, ceo at Cereno Scientific, said the paper represents the first formal scientific introduction of CS014. He said: “It is the first formal scientific introduction of our NCE CS014 to the global community and further validates the strength of our HDAC inhibitor platform.” He added: “Published data is a critical component of partner discussions, regulatory interactions, providing credible scientific status.”

Cereno Scientific is preparing for Phase 2 development of CS014, with an initial clinical focus on idiopathic pulmonary fibrosis. The company believes the published data support broader potential for the compound across severe cardiovascular and pulmonary diseases characterised by thrombosis, vascular remodelling and fibrosis.