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OUR MISSION

ATXA Therapeutics Ltd. is a company on a mission... to offer new hope to the PAH patient.

Current therapies for Pulmonary Arterial Hypertension (PAH) typically act to increase vasodilation to lower pulmonary vascular resistance and improve exercise capacity.

 

They do little to treat the other major clinical features of the disease or to reduce disease progression.

 

Patient outcomes remain poor - and these current therapies often have severe side effects.

 

Therefore, there is an urgent unmet medical need for new targets and therapeutic drugs that offer greater tolerability/compliance and overall efficacy.

New Thinking - New Therapies 

An exciting alternative approach to achieving improved vasodilation is to reduce the vasoconstrictive potential by antagonizing/inhibiting the action of the prostanoid thromboxane A2 (TXA2).

 

By binding to the T Prostanoid receptor (the TP), TXA2 signals through elevations in intracellular calcium mobilization and confers multiple actions including serving as a potent vasoconstrictor, as a driver of platelet aggregation and as a pro-mitogenic and pro-inflammatory mediator.

 

Hence, mechanistically, TP antagonists should act as ideal therapeutic drugs for PAH inhibiting the excessive vasoconstriction and endothelial and smooth muscle cell hyper-proliferation, limiting the pulmonary vascular remodeling, inflammation and fibrosis, while also preventing the associated in situ micro-vessel thrombosis.

The potential importance of TXA2 as a driver of disease pathology is indicated by findings in pediatric patients with PAH caused by congenital heart disease defects. These patients typically have elevated urinary and plasma levels of thromboxane B2, the stable end-product metabolite of TXA2.

 

Moreover, results from the recent randomized clinical trial of Aspirin and Simvastatin (ASA-STAT) showed that PAH patients with higher levels of TXA2 were associated with more advanced disease, and with worse clinical outcome/survival. Hence, these latter clinical observations further endorse ATXA Therapeutics Limited's selected drug target, the T Prostanoid receptor/TP, for treatment of PAH.

Antagonists of the TP are predicted to be potent inhibitors of vasoconstriction, platelet aggregation, inflammation and fibrosis, offering benefits to patients through a reduced potential for excessive vasoconstriction, in situ-thrombosis and localized inflammation, as well as reduced endothelial and smooth muscle cell proliferation resulting in reduced vessel remodeling and occlusion in the PAH lung.

 

Hence, TP antagonists may treat many of the clinical hallmarks of PAH, including inhibiting the excessive vasoconstriction and pulmonary artery remodeling, the in-situ thrombosis, fibrosis and inflammation.

 

Moreover, and also critically, the TP not only mediates the actions of TXA2 but also mediates the actions of the isoprostane 8-iso-prostaglandin (PG) F2 alpha (also termed 15-F2t-isoprostane), a non-enzymatic-, free-radical- derived product of arachidonic acid produced in abundance during oxidative injury/hypoxia.

Thus, TP antagonists will have the additional benefits over all existing PAH therapies in that they will inhibit the adverse actions of this free-radical derived 8-iso-PGF2a that is present in high amounts in the hypoxic environ of the PAH lung.

The Future of PAH Therapy

ATXA Therapeutics has developed a novel series of highly selective antagonists of the TP receptor. Amongst ATXA’s TP antagonist series is the lead candidate drug NTP42, as well as back-up candidates.

NTP42 and other candidates in this series have been extensively evaluated and have been confirmed to display potent antagonist activity, excellent specificity and pharmacokinetic/toxicology profiles in a range of in vitro, ex vivo and in vivo preclinical models following oral delivery, including in the proposed orphan indication PAH.

ATXA has confirmed the benefit of NTP42 in 2 gold-standard preclinical models of PAH, namely the Sugen-Hypoxia (SuHx) and Monocrotaline (MCT) models, where it has shown benefit as a mono-therapy and as a dual-therapy with other standard-of-care drugs.

ATXA Therapeutics Limited is now focused on advancing clinical trials and to secure marketing authorization for NTP42 in the treatment of Pulmonary Arterial Hypertension (PAH), serving a previously unmet medical need by offering improved treatment options to the prescribing physician and new hope for the PAH patient.

ATXA Therapeutics Ltd. is a company on a mission... to offer new hope to the PAH patient.