A first-in-class treatment for PAH
ZMA001 is a first-in-class therapeutic with novel MOA, which can eliminate the root pathologic cause of pulmonary arterial hypertension (PAH).
ZMA001 is a human monoclonal antibody designed to control or inhibit inflammation responses in pulmonary blood vessels by blocking Lysyl-tRNA synthetase (KARS1)-dependent infiltration of monocytes and macrophages.
ZMA001 specifically targets membrane-exposed KARS1 without affecting its catalytic activity for protein synthesis. It can assure specificity toward response, disease indication, immune system, and target biology without inducing the systemic hypotension frequently observed with other typical treatments using vasodialators.
A departure from currently available therapies
PAH is a disease characterized by high blood pressure and fibrosis of the pulmonary arteries. The resulting heart failure is the main cause, leading to PAH patient deaths with 5-year survival rates of about 57% after diagnosis.
Currently available therapies are palliative and act to temporarily reduce blood pressure by dilating blood vessels. There is therefore a high unmet medical need for therapies that can increase survival rate by targeting the pathophysiological cause of PAH with low side effects.
Since existing therapies have significant side effects, our approach promises to be superior and will improve both the quality of life and survival of affected patients. In addition, ZMA001 does not seem to affect other immune cells except for the monocytes and macrophages that are actively involved in the pathology of fibrosis, with no indication of systemic immune suppression.
While we focus on PAH as the primary indication for strategic reasons, this drug will also be applicable to other fibrotic diseases.
In vivo efficacy and safety
ZMA001 treatment significantly improves PAH measurements, eg, right ventricular end-systolic pressure, monocytes and macrophages infiltration to the lung, and fibrosis in multiple PAH animal models.
Moreover, ZMA001 increases animal survival and shows a synergic effect when combined with sildenafil, the current standard of care vasodilation drug.
The 4-week repeated toxicity study in rats and monkeys revealed no adverse symptoms even at 100 mg/kg injection of ZMA001, demonstrating the strong safety profile of ZMA001.
