1st human trial of ZMA001 for PAH starts to dose healthy adults

Still-recruiting Phase 1 trial to test ZMA001's safety, pharmacological properties

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by Andrea Lobo |

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The first healthy volunteer has been dosed in a Phase 1 trial testing ZMA001, Zymedi’s first-in-class investigational therapy for pulmonary arterial hypertension (PAH).

The trial (NCT05967299), still recruiting participants at a clinical center in Bethesda, Maryland, will evaluate the safety, tolerability, and pharmacological properties of ZMA001. It seeks 96 healthy participants, ages 18 to 60 years, and is expected to be concluded in 2026.

“We are scheduled to assess the safety and tolerability of ZMA001 through dose escalation clinical trials, systematically observing adverse reactions as dosage increases,” Sunghoon Kim, PhD, Zymedi’s founder and CEO, said in a company press release.

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Current treatments manage symptoms of PAH

PAH is characterized by the narrowing of pulmonary arteries, the blood vessels that transport blood through the lungs. It is a type of pulmonary hypertension, a chronic and progressive disorder characterized by high blood pressure in pulmonary vessels.

Currently approved treatments for PAH help manage its symptoms, which can include shortness of breath, fatigue, muscle weakness, chest pain, fainting, and heart failure. The medications are designed to reduce blood pressure but do not address the underlying causes of the disease.

ZM001 is a human monoclonal antibody intended to reduce inflammation and tissue scarring in people with PAH, by blocking lysyl-tRNA synthetase (KARS1), a pro-inflammatory enzyme that is specific to immune cells called monocytes and macrophages.

According to Zymedi, this new mechanism of action may assure a specific response in controlling inflammation in pulmonary blood vessels, without leading to low blood pressure, as often occurs with currently used vasodilators, or medications that widen blood vessels. The company further states that, by addressing the root cause of PAH, ZMA001 may improve survival and quality of life in this patient population.

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ZMA001 showed benefits in PAH animal models

Studies in PAH animal models have shown treatment with ZMA001 reduced immune cell infiltration to the lungs and tissue scarring (fibrosis), while improving heart health. Moreover, the treatment extended survival and showed a positive effect when combined with sildenafil (sold as Revatio and Liqrev), a standard vasodilator for PAH.

Also, a four-week toxicity study revealed ZMA001 was safe in rats and monkeys, without any adverse events, according to the company.

The Phase 1 trial will assess different doses of ZMA001, ranging from 1.5 mg/kg to 20 mg/kg, or a placebo, administered by a one-time intravenous (into-the-vein) infusion. Participants will be followed for 113 days (slightly less than four months).

The study is the first time ZMA001 is administered to people, Zymedi noted, and was the result of a collaboration between the company and the National Heart, Lung, and Blood Institute, a part of the National Institutes of Health. Last year, both organizations reached a Cooperative Research and Development Agreement to advance the development of ZMA001.

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