Inhaled rentosertib trial in China to test IPF therapy in patients, volunteers
Chinese authorities OK first-in-human study of new drug formulation
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Insilico Medicine will soon launch an early clinical trial in China to test an inhaled version of its therapy candidate rentosertib in healthy volunteers and people with idiopathic pulmonary fibrosis (IPF).
This announcement follows the clearance of the company’s investigational new drug (IND) application by the Chinese Center for Drug Evaluation (CDE), which allows Insilico to begin clinical testing of the therapy in humans.
The inhaled treatment is designed to reduce lung scarring, or fibrosis, which may help ease symptoms in people with IPF.
“We are pleased to receive CDE IND approval for Rentosertib inhalation solution.” Feng Ren, PhD, coCEO and chief scientific officer of Insilico Medicine, said in a company press release announcing the regulatory decision.
The company noted that its “rentosertib inhalation solution is the 13th program from Insilico’s AI-driven pipeline to receive IND clearance.” AI is an acronym for artificial intelligence.
A chronic disorder, pulmonary fibrosis (PF) is marked by lung scarring, which makes it difficult for patients to breathe. In idiopathic PF, the underlying cause of fibrosis is unclear.
Trial of inhaled rentosertib follows testing of oral formulation
Rentosertib, formerly known as ISM001-055, is a small molecule designed to reduce fibrosis by blocking the activity of a protein called TNIK. Insilico developed the therapy using AI tools.
“The CDE IND clearance for the Rentosertib inhalation solution further validates Insilico Medicine’s sustainable, scalable, and reproducible AI-driven drug discovery and development workflow,” said Alex Zhavoronkov, PhD, Insilico’s founder and CEO. “With our proprietary AI models, we empower the whole process from target discovery to clinical development, expanding into formulation types and geographic areas.”
In addition to this inhalation version, Insilico is developing an oral formulation of rentosertib, which has been tested in IPF patients in a Phase 2a clinical trial (NCT05938920). The results from that trial, published last year, indicated that the oral therapy was generally well tolerated and tended to improve lung function measures versus a placebo. In fact, lung function was seen to worsen over time in participants given the placebo.
“In prior clinical studies, oral Rentosertib showed good tolerability, a favorable [pharmacological] profile, and dose-dependent efficacy trend, strengthening our confidence in its mechanism and clinical potential,” Ren said.
Insilico is continuing to develop oral rentosertib, with plans to initiate Phase 3 clinical testing later this year. But the company is also developing the inhaled version of the drug, which will now enter early clinical testing.
Inhaled drugs are generally more complicated to develop than oral medicines, but inhalation means the medication is being administered directly into the lungs, where it’s needed most. That’s expected to maximize efficacy and minimize side effects due to off-target effects elsewhere in the body.
The inhalation solution is designed for targeted lung delivery, with the goal of … faster onset at lower doses while reducing systemic exposure and optimizing the benefit-risk profile.
The upcoming trial will consist of two parts. The first will test single and multiple doses of inhaled rentosertib in healthy volunteers, with the main goal of evaluating the safety and pharmacological properties of this formulation. The second part will then test multiple doses of inhaled rentosertib in people with IPF.
The company said the study will enroll about 80 participants, but did not specify how many will be healthy controls and how many will be IPF patients.
“The inhalation solution is designed for targeted lung delivery, with the goal of achieving higher pulmonary exposure and faster onset at lower doses while reducing systemic exposure and optimizing the benefit-risk profile. In parallel, we continue to advance the oral Rentosertib program and remain on track to initiate Phase [3] trials in the second half of this year,” Fen said.
