Cereno widens clinical program as competition heats up in lung disease

CS014 was initially being investigated for people with idiopathic pulmonary fibrosis (IPF), and in an upcoming phase 2 study, it will also admit patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). This therapeutic broadening is “intended to support a more clinically relevant Phase II program, strengthen the development potential of CS014, and address a patient population with very high unmet medical need,” stated the press release.

Positioning CS014 in ILD

CS014 is an investigational small molecule that inhibits the enzyme histone deacetylase, or HDAC, involved in the modulation of gene expression. HDAC inhibitors have been studied as therapeutics for cancer, inflammation, and, as in the case of CS014, for cardiovascular and fibrotic diseases. By modulating gene expression, CS014 has the potential to reduce fibrosis, inflammation, and tissue remodeling in the lungs, addressing the root causes of disease rather than just alleviating symptoms. This mechanism positions CS014 as a differentiated therapy in areas of high unmet medical need.

In a Phase I trial completed last year, Cereno showed that single and multiple oral doses of CS014 were safe and well-tolerated in healthy volunteers. CS014 also achieved exposure levels expected to impact pulmonary vascular remodeling and fibrosis, key drivers of rare cardiopulmonary diseases.

Idiopathic pulmonary fibrosis (IPF), the initial target disease, is part of the umbrella group of interstitial lung diseases (ILDs). ILDs are rare lung disorders characterized by inflammation and scarring of lung tissue. Idiopathic pulmonary fibrosis (IPF) is a severe and progressive form of ILD with unknown cause, marked by irreversible lung fibrosis and poor prognosis. But another serious complication in ILD patients is pulmonary hypertension associated with ILD (PH-ILD), the disease involved in Cereno’s clinical expansion. PH-ILD manifests with increased pressure in the lung blood vessels, which strains the heart and further worsens outcomes. Together, IPF and PH-ILD represent high unmet medical needs, highlighting opportunities for therapies that can slow fibrosis and address associated vascular complications.

This therapeutic expansion comes after recent FDA approval of Boehringer Ingelheim’s Jascayd (nerandomilast) for progressive pulmonary fibrosis (or PPF), a subset of ILDs. Only months earlier, Jascayd had been FDA-approved to treat adults with idiopathic pulmonary fibrosis (IFP).

Unlike CS014, which targets gene expression, Jascayd is a selective PDE4B inhibitor, one of the phosphodiesterase 4 family enzymes that break down cyclic AMP (cAMP). By elevating intracellular cAMP levels, Jascayd reduces the expression of pro-fibrotic growth factors and inflammatory cytokines, which are overexpressed in IPF, exerting both anti-fibrotic and immunomodulatory effects.

Jascayd became the first new therapy for IPF to be approved in over a decade. It has also received approval in China, and regulatory applications for IPF and PPF are currently under review in the European Union, the UK, Japan, and other regions, with further approvals expected in 2026.

A crowded PAH market

Despite all the activity around CS014, Cereno’s lead candidate is CS1, an oral therapy being investigated in a phase 2 clinical trial for the rare disease pulmonary arterial hypertension or PAH. PAH is a specific type of pulmonary hypertension, a condition characterized by elevated blood pressure in the arteries of the lungs.

PAH is a crowded market space, with some approved therapies, such as United Therapeutic’s Tyvaso (treprostinil), Liquidia’s Yetrepia (treprostinil), and Merck’s Winrevair (sotatercept). Of note, Yutrepia and Tyvaso are also approved for PH-ILD.

In a completed Phase IIa study, CS1 showed a favorable safety and tolerability profile, with data suggesting potential disease-modifying effects. Findings from both preclinical and clinical studies support the ability of CS1 to reverse abnormal vascular remodeling, a central driver of disease progression in PAH.

The company plans to start a phase 2b trial for CS1 in PAH in Q2 2026, and expects to initiate the phase 2 trial for CS014 in IPF and PH-ILD sometime in Q1 2027.

CS014 and CS1 place Cereno in two increasingly competitive cardiopulmonary arenas, where recent approvals have raised the bar for differentiation. Cereno is positioning itself to differentiate through disease-modifying mechanisms rather than symptomatic relief, an angle that could prove decisive as both markets continue to evolve.