Molecure seeks FDA OK for Phase 2 trial in pulmonary sarcoidosis
Biotech to test small molecule OATD-01 in proof-of-concept study
Molecure is seeking permission from the U.S. Food and Drug Administration (FDA) to conduct a Phase 2 clinical trial of its oral treatment candidate OATD-01 in people with pulmonary sarcoidosis.
The request came in the form of an investigational new drug application (IND) submitted to the FDA. Should the proof-of-concept trial be cleared, the company anticipates it will launch in the U.S. and the European Union by the end of the year.
“This IND application brings us a step closer to a new treatment option for underserved sarcoidosis patients,” Samson Fung, MD, Molecure’s chief medical officer and member of the management board, said in a company press release.
“We are excited about our plans to advance OATD-01 into a Phase 2 trial as we believe this highly promising new agent could play a key role in the treatment of this rare disease, improving symptoms as well as quality of life and potentially stopping disease progression,” Fung added.
OATD-01 seen to reduce lung granulomas in mice
All forms of sarcoidosis are characterized by the buildup of small clumps of inflammatory cells, called granulomas, in the body’s tissues. When the granulomas are primarily found in the lungs, it’s known as pulmonary sarcoidosis.
Patients typically experience symptoms such as shortness of breath, cough, chest pain, or wheezing. In severe cases, pulmonary sarcoidosis can lead to scar tissue (fibrosis) building up, causing a permanent loss of lung function.
Disease-modifying treatments for the condition are lacking, with none having received FDA approval. Instead, patients typically are given steroids or other immunosuppressive therapies for symptom management. But their effectiveness is often limited, and many pulmonary sarcoidosis patients experience side effects from such treatment.
“There are currently no approved therapies for sarcoidosis, and while steroids are often used, they have serious side effects and deliver only short-term benefits with little evidence of extended therapeutic efficacy,” said Marcin Szumowski, PhD, Molecure’s CEO.
“As a result, there is a significant unmet need for better treatments that can prevent disease progression,” Szumowski said.
OATD-01 is an orally available small molecule originally discovered and developed by Molecure, previously known as OncoArendi Therapeutics. While the therapy’s further development was, at one point, shared between Molecure and another biotech called Galapagos, the Poland-based company regained the exclusive global rights to OATD-01 in mid-2022.
Taken orally once a day, OATD-01 works by suppressing the activity of chitotriosidase, known as CHIT1, an enzyme involved in the defense against certain microbes that also serves other immune functions.
It’s been implicated in a number of chronic lung disorders, including pulmonary sarcoidosis and idiopathic pulmonary fibrosis (IPF), a disease of the respiratory system.
In sarcoidosis patients, the enzyme is found to be elevated in the blood and lungs, where its activity levels have been linked to disease activity and granuloma burden.
The company therefore believes that by blocking the enzyme, OATD-01 has potential for slowing the progression of various lung diseases.
We believe that OATD-01, which has demonstrated efficacy in several pre-clinical models, could alter the fate of sarcoidosis patients by becoming the new standard of care.
Indeed, preclinical studies have demonstrated that OATD-01 treatment eased inflammation in addition to decreasing the number of lung granulomas in mouse models of sarcoidosis-like disease. It also reduced the activity of sarcoidosis-associated genes in the mice. Moreover, the therapy was shown to have anti-fibrotic effects.
“We believe that OATD-01, which has demonstrated efficacy in several pre-clinical models, could alter the fate of sarcoidosis patients by becoming the new standard of care,” Szumowski said.
Treatment deemed safe in early clinical trials
The experimental therapy has earned orphan drug designation from the FDA for the treatment of both sarcoidosis and IPF. That status offers incentives to speed the treatment’s clinical development toward regulatory approval.
After single ascending doses of the treatment were deemed safe in a Phase 1a clinical trial, a Phase 1b study evaluated the safety and pharmacological properties of OATD-01. The therapy was given once daily, for 10 days, in 24 healthy volunteers.
The results showed that the treatment was safe at either of two tested daily doses — 25 and 50 mg — and led to very strong CHIT1 suppression. Mathematical modeling suggested that OATD-01 also may effectively reduce CHIT1 at even lower doses, although this was not directly tested.
Should it be cleared, the future, global Phase 2 trial will evaluate OATD-01’s safety and effectiveness against a placebo in about 90 people with active pulmonary sarcoidosis.
Its main goal will be to evaluate the reduction in granuloma-associated inflammation in the lungs, as assessed by PET or CT imaging, after 12 weeks or about three months of treatment. That goal already has been cleared by the FDA in a pre-IND meeting, according to Fung.
The trial would be expected to finish in the first half of 2025.
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