Phase 1 trial of potential treatment for IPF moves forward ‘without any safety concerns’

Key takeaways:

• Prior to this trial, CS014 had positive outcomes in an animal model.
• Researchers are moving onto part two of the phase 1 trial in humans, which will study CS014 when given as a multiple ascending dose.

No safety concerns emerged in part one of the phase 1 trial assessing CS014, a histone deacetylase inhibitor that has potential in treating idiopathic pulmonary fibrosis, in healthy individuals, according to a press release.

Prior to this trial, the histone deacetylase inhibitor (HDACi) CS014 (Cereno Scientific) was tested in animals and had positive outcomes, Sten R. Sörensen, BS, CEO of Cereno Scientific, told Healio.

“CS014 demonstrates a strong efficacy for reversal of pulmonary vascular remodeling in a translationally validated disease animal model in pulmonary arterial hypertension — the Sugen/Hypoxia rat — and therefore possesses potential disease-modifying effects,” Sörensen said. “This includes a robust dose-dependent reversal in the occurrence of plexiform lesions and anti-fibrotic effects.”

Sörensen also said blood vessels were impacted by CS014.

“It shows in vivo anti-thrombotic effects across a broad range of blood vessels from low- to high-sheer rate vessels,” Sörensen told Healio. “Very importantly, these effects are seen in the absence of increased bleeding risk.”

This drug candidate comes at an opportune time as Sörensen said in the release that there is a need for a new treatment for IPF. Currently, patients with this disease only have two FDA-approved treatments — nintedanib (Ofev, Boehringer Ingelheim) and pirfenidone (Esbriet, Genentech) — both of which could use improvement, according to Sörensen.

“The two available drug treatments have modest effect on the disease progression, dose-limiting toxicity and poor tolerability,” Sörensen told Healio. “Additionally, the current treatments have frequent side effects that carries an impact on patients’ daily life.”

Key characteristics of CS014 outlined by Sörensen include a favorable safety profile, a favorable tolerability profile, once-daily dosing and oral administration. This drug can also be combined with standard of care.

“There is a need for safe and well-tolerated treatments with both symptomatic relief and profound effect/stabilization of disease progression,” Sörensen told Healio. “We believe that CS014, as a new chemical entity, can meet this high unmet need for safe, well-tolerated disease-modifying treatments for IPF and transform the IPF treatment landscape.”

According to Sörensen, the potential of HDACi as a treatment for IPF lies in its potential ability to reverse the root mechanism of disease progression.

“HDACi increases histone acetylation, which in turn modulates the expression of genes that counteract proliferation of pulmonary arterial smooth muscle and endothelial cells, endothelial dysfunction, inflammation, fibrosis and thrombosis; key drivers of cardiovascular and pulmonary disease progression,” he told Healio.

“CS014 is an enhanced HDACi with a profile highly suited for IPF treatment,” Sörensen continued.

In the first part of the open-label phase 1 trial, researchers assessed 30 healthy individuals to determine three different profiles of CS014 when given as a single ascending dose: safety, tolerability and pharmacokinetic.

Finding that the drug has “an acceptable safety profile,” researchers are moving onto part two of the trial, which will study CS014 when given as a multiple ascending dose (MAD), according to the release.

“Part two of the phase 1 will be the MAD with 1 week dosing and some pharmacodynamic evaluation related to the already shown anti-thrombotic effects,” Sörensen told Healio. “The MAD part will help identify the dose levels that can be safely administered over time.”

According to the release, mid-2025 is the expected time of phase 1 completion. Clinicians can expect to see topline results following the conclusion of the trial.

“HDAC inhibitors, and with that CS014 as an innovative development in this field, could represent a transformative addition to the limited treatment options for IPF, with the potential to slow disease progression, improve lung function and enhance patients’ quality of life,” Sörensen told Healio.