FDA clears GRI Bio’s Phase 2 trial of natural killer T-cell targeted therapy

Multi-center Phase 2a biomarker study of GRI-0621 to launch this month

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by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has given GRI Bio the green light to conduct a Phase 2 trial of its investigational natural killer T-cell (NKT)-targeted therapy, GRI-0621, in people with idiopathic pulmonary fibrosis (IPF).

With the clearance of its investigational new drug (IND) application, the company is planning to launch the multi-center Phase 2a biomarker study before the end of the year.

“Clearance of our IND application for GRI-0621 represents a significant milestone for the Company and for our innovative pipeline of NKT cell modulators,” Marc Hertz, PhD, GRI Bio’s CEO, said in a company press release. “We look forward to initiating patient enrollment before year end and potential future data releases in 2024.”

A chronic lung disease, IPF is characterized by the progressive buildup of scar tissue (fibrosis) in the lungs due to an unknown cause. Symptoms include breathing difficulties, shortness of breath, and cough.

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Immune NK T-cells may be therapeutic target for IPF

Currently available treatments come with significant side effects

Currently available treatments are limited. The two approved IPF-targeted therapies, Ofev (nintedanib) and Esbriet (pirfenidone), have significant side effects and don’t positively affect survival, according to GRI Bio.

“The ability to provide this population of patients with options is really, really important,” Albert Agro, PhD, GRI Bio’s chief medical officer, said in a company webcast.

A growing body of evidence has implicated NKT cells in IPF. These immune cells are among the body’s first line of defenders that work to fight off potential threats. A certain subset of them, called type 1 invariant NKT (iNKT) cells, are believed to trigger a cascade of cellular events that drive inflammation and fibrosis in mice and IPF patients.

A study recently conducted by GRI Bio and collaborators showed NKT cells are found at a higher frequency in the lungs of IPF patients compared with people in the general population.

Moreover, NKT cells from IPF patients had higher activity of genes involved in fibrosis and inflammation, and their prevalence correlated with the number of another type of inflammatory immune cells called macrophages.

We look forward to initiating patient enrollment before year end and potential future data releases in 2024.

GRI-0621 designed to lead to suppressed activity of iNKT cells

GRI-0621 is a small molecule designed to mimic the activity of retinoid acid receptors beta and gamma, which work to suppress the activity of iNKT cells.

As such, GRI Bio believes the therapy will help ease fibrosis in people with IPF, with the potential to expand its development to other fibrotic diseases.

After being found to ease fibrosis in preclinical models, the experimental oral therapy was tested in a small placebo-controlled Phase 2a trial (NCT02949375) that enrolled 14 people with a chronic fibrotic liver disease. There, the treatment was found to improve liver function and reduce inflammation, according to GRI Bio.

The upcoming Phase 2a trial will enroll about 36 IPF patients, who will be randomly assigned in a 2:1 ratio to receive oral GRI-0621 (4.5 mg) or a placebo once daily for 12 weeks, or about three months.

Its main goal is to evaluate GRI-0621’s safety and tolerability, as assessed by clinical labs, vital signs, and side effects, after 12 weeks of treatment. An interim analysis will be conducted after about 24 participants, including eight on the placebo, have completed six weeks of treatment.

Secondary measurements will include assessing changes in blood biomarkers, GRI-0621’s pharmacological properties, and the therapy’s inhibition of iNKT cell activation in the blood.

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Sub-study to examine iNKT cells in lung fluid after 12 weeks of treatment

A sub-study involving up to 12 eligible IPF patients will examine the number and activity of iNKT cells in lung fluid after 12 weeks of treatment. An exploratory efficacy endpoint will be to evaluate the effects of GRI-0621 on lung function throughout treatment.

Interim data are expected in the first half of next year, with top-line results anticipated in the second half of 2024.

“Getting clearance from the FDA is a really important step, but equally important is getting the IPF community behind our clinical study …, getting them excited about the approach,” Hertz said. 

To that end, the GRI Bio team is actively working to identify clinical trial sites in the U.S. and other countries, such as the U.K. and Australia.

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