Novel HDACi CS014
The investigational drug candidate CS014 belongs to Cereno’s HDAC inhibitor program capitalizing on the principle of epigenetic modulation. In March 2019, CS014 was acquired from Emeriti Bio and is being developed in a collaboration between Cereno, Emeriti Bio and University of Michigan. The drug candidate CS014 is being developed as a treatment to effectively prevent arterial and venous thrombosis without increasing the risk of bleeding.
The innovative drug candidate represents a groundbreaking approach to antithrombotic treatment potentially without the associated increased risk of bleeding in humans. CS014 is a new chemical entity with a multi-fold mechanism of action as an epigenetic modulator – regulating platelet activity, fibrinolysis, and clot stability for the prevention of thrombosis without increased risk of bleeding as documented in preclinical studies. Given the potential for the additional disease-modifying properties seen with HDAC inhibition, additional cardiovascular benefits of CS014 may be expected, including amelioration of inflammation, fibrosis, vascular changes and elevated blood pressure. HDAC inhibition as thrombosis prevention has the opportunity to fundamentally change the thrombosis prevention landscape and meet a major unmet medical need.
In 2023, new positive preclinical data were presented with CS014 as an effective HDAC inhibitor that inhibits platelet activity, small and large vessel thrombosis while maintaining hemostasis in a dose-dependent manner. Also, when combined with rivaroxaban, CS014 inhibited the formation of platelet and fibrin-rich thrombosis without adding to the bleeding risk. These cumulated data shows that CS014 has the potential to enrich the toolbox of antithrombotic therapies in both venous and arterial thrombosis. With clinical use of the HDAC inhibitor CS014, through epigenetic modulation, it would be possible to prevent thrombosis without an increased risk of bleeding, a much desired unmet medical need. Additional preclinical and clinical studies will be conducted to determine the first indication where CS014 has the greatest potential as a treatment to prevent thrombosis.
Preparations for entering clinical first-in-human Phase I study are ongoing. The preclinical safety program for CS014 was successfully completed in December 2023. The safety documentation is a key component needed to apply for permission from regulatory authorities to start a first-in-human Phase I study.
Novel IP Receptor Agonist CS585
Drug candidate CS585 has, in initial in vivo animal models, demonstrated the potential to significantly improve disease mechanisms relevant to selected cardiovascular diseases. CS585 is a prostacyclin receptor agonist that has been documented in several preclinical studies to target the IP receptor for prevention of thrombosis without increased risk of bleeding. The drug candidate CS585 has not yet been assigned a specific indication for clinical development as evaluation in the preclinical program is still ongoing.
In preclinical studies, CS585 has shown efficacy by stimulation of the prostacyclin (IP) receptor and thus prevents thrombosis without increased risk of bleeding. Preclinical data were presented at the scientific congress EHA 2022 and the US-based scientific congress ACC.23/WCC in March 2023. These data demonstrate that CS585 may have the potential to become one of the most effective PRA treatments for the indications PAH and thrombosis prevention.
In early April 2023, Cereno signed a license agreement for drug candidate CS585 with the University of Michigan. The agreement provides Cereno exclusive rights to further development and commercialization of CS585. In conjunction, the Company extends the preclinical development collaboration agreements with University of Michigan.
In early November 2023, CS585 was highlighted by top-tier medical journal Blood as a promising novel anti-thrombotic strategy without risk of bleeding.
In December 2023, preclinical data was presented that conclude that CS585 provides a new option of activating the IP receptor to decrease platelet reactivity and could represent the first viable option for targeting the IP receptor on platelets. For the first time, a head-to-head comparison of CS585, a novel IP receptor agonist, was conducted with the FDA-approved IP receptor agonists selexipag and iloprost. The preclinical results with CS585 indicate a favorable profile for inhibiting platelet activation and clot formation and demonstrate a sustained duration of action in mice in the ability to inhibit platelet activation through multiple routes of administration.