CS1: A step closer to Phase IIb
CS1, Cereno’s lead asset, is an HDACi designed to leverage the principles of epigenetic
modulation to reverse pathological remodelling. It is a delayed immediate release
formulation of valproic acid, and holds promise as a potential disease-modifier for
PAH. Backed by positive Phase IIa top-line data in September 2024 and subsequent incremental
data presented in Q125 specifically related to the drug’s potential to produce reverse
vascular remodelling and improve right heart function, the focus in recent months
has been on preparing to advance CS1 to Phase IIb. We direct readers to our last update note for more details on the Phase IIa trial and subsequent incremental data.
During the quarter, Cereno focused on continued treatment and monitoring of patients
enrolled in the EAP, which was available to the 21 patients who completed the 12-week
treatment as part of the Phase IIa trial (CS1-003). We understand that as of December
2024, a total of 10 patients had enrolled for the EAP and a four-month follow-up update
for these patients is expected by mid-2025, a key upcoming inflection point for Cereno.
We believe this long-term data from the EAP is key to establishing continued benefits
from the treatment with CS1. We also remind readers that in February 2025, a sub-study to the EAP, using novel
imaging technology developed by Fluidda, was initiated, to visualise the effect of
CS1 on inducing long-term reverse remodelling in PAH. We understand that the sub-study
will enrol five to seven of the 10 patients in the EAP and results are expected in
H126.
In April 2025, Cereno successfully completed its planned Type C meeting with the FDA,
noting the regulator’s alignment with the Phase IIb study design and planned steps
for clinical development. This was confirmed by the meeting minutes released recently, with the FDA reported to have endorsed Cereno’s Phase IIb plans. Note that unlike
Type A and Type B meetings, Type C meetings are not strictly required, although they
offer the opportunity to engage with the regulators to ensure agreement on study objectives,
design and endpoints. This may support the likelihood of a successful outcome.
We expect the next step for Cereno will be the filing of the IND application for the
planned Phase IIb trial and believe that the additional data from the EAP may be used
as part of the regulatory dossier for this next stage of development. While the Phase
IIb study design has not been disclosed as yet, we anticipate it to be a placebo-controlled
trial designed to further evaluate the encouraging efficacy signs seen in the CS1-003
trial (including reverse vascular remodelling and improvement of right heart function).
We also see the possibility of the trial being increased duration (around 24 weeks
as compared to the 12-week CS1-003 study) which may potentially be driven by insights
from the longer-term data from the EAP. Cereno plans to commence the Phase IIb trial
in H126 and we assume this will be self-sponsored. However, should Cereno receive
interest from a prospective partner and have shareholder support, a licensing deal
prior to the Phase IIb initiation is also a distinct possibility.
We note that while other products have been approved for PAH (notably the FDA approved
Merck’s sotatercept, brand name Winrevair, in March 2024), the established safety
profile of VPA and potential for oral administration of CS1 could offer a competitive
edge, especially if further clinical development efforts provide further evidence
of its disease-modifying properties.
CS014: closing in on Phase I readouts
CS014 is the second candidate in Cereno’s HDACi portfolio, and is a proprietary new
chemical entity and deuterated valproic analogue of VPA. IPF was nominated as the
target indication for CS014 at the company’s capital markets day in 2024, whereby
it announced a strategic pivot to specialise in the rare disease space. The Phase I study (designed to evaluate
safety, tolerability, pharmacokinetics/PK and pharmacodynamics/PD of CS014 in 48 healthy
volunteers) commenced in June 2024 and was recently concluded. The SAD part of the
study, which evaluated safety, tolerability and PK of CS014 in 30 participants, was
completed in February 2025 and showed no safety concerns. More recently, the MAD part of the
study, which also assessed PD of CS014 in 18 participants over a seven-day period,
concluded in April 2025. Data management and analysis is currently ongoing, and the
Q125 update confirmed that the top-line results are on-track to be reported in June
2025, another near-term catalyst for Cereno.
Should the Phase I results be favourable, Cereno intends to undertake a Phase II study
in H126, which will include IPF patients as part of its strategic focus on rare diseases.
We believe that toxicology studies required prior to the initiation of the Phase II
study have already commenced. Currently, there are only two drugs approved for IPF,
Esbriet (pirfenidone) and Ofev(nintedanib), with no new approvals in the past decade.
While the approved drugs help slow disease progression, neither halts nor reverses
it. Moreover, these drugs are associated with severe side effects and tolerability
issues. This offers a potentially sizeable opportunity for Cereno, should CS014 demonstrate
disease modification in IPF patients.
CS585: bolstering the preclincial data package
The company’s third asset, CS585, is an oral, selective and potent inhibitor of the
prostacyclin (IP) receptor, in the preclinical stages of development. A precise indication
is yet to be determined for CS585, but early-stage research has showcased its promise
as a potential treatment to prevent thrombosis without increased risk of bleeding,
aiming to address a key limitation of current anti-thrombotic medications. The promise
it has shown in preclinical studies has been recognised with a publication in the
high-impact factor journal Blood. The latest updates demonstrated that CS585 inhibits platelet activation and clot formation for up to
24 hours after being administered, and showed that it is highly selective for the
IP receptor, providing sustained prevention of thrombus formation. We understand the
drug continues to be evaluated in the preclinical setting, and we await further information
from management on the plans to progress to the clinic.
