Constant Therapeutics has said that its lead drug candidate, TXA127, is set to be part of a US National Institute of Health (NIH)-funded ACTIV-4d clinical trial for Covid-19 in the country.

The drug candidate targets renin-angiotensin-aldosterone system (RAAS), which becomes irregular on Covid-19 infection.

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Human peptide angiotensin-(1-7) drops when SARS-CoV-2 attaches to the angiotensin-converting enzyme 2. This causes fatal complications, such as pulmonary oedema, thromboembolic complications, and severe cardiac injury.

The active ingredient of TXA127 is human peptide angiotensin-(1-7), the company noted.

This large NIH trial is assessing various compounds to identify effective treatments for SARS-Cov-2 and its variants. The TXA127 arm will enrol 300 subjects in around 60 sites in the US.

The objective is to gain insights into the drug’s effect on Covid-19 patients’ recovery along with information on the link between restoring RAAS balance and patient outcomes.

Constant Therapeutics founder and CEO Dr Rick Franklin said: “Supplementing Angiotensin-(1-7) with TXA127 has the potential to reverse the disruption caused by Covid-19.

“Beyond the acute distress that characterises Covid-19, other longer-term pathologies associated with the disease include inflammation, large vessel strokes, microthrombosis and effects on the central nervous system, all of which may be the result of reduced levels of Angiotensin-(1-7) in infected patients and may be treatable with TXA127.”

In preclinical studies, including acute lung injury models, the drug was found to lower fibrosis, balance endothelial and epithelial barrier function and mitigate inflammation, the company noted.

Separately, Inovio has reported that its pan-Covid-19 vaccine candidate, INO-4802, stimulated potent neutralising antibodies and T cell responses against the SARS-CoV-2 strain and variants of concern in preclinical models.

Inovio said that this data signifies the vaccine’s ability to generate cross-reactive immune responses against the original Wuhan strain and B.1.1.7 (UK variant), B.1.351 (South African variant) and P.1. (Brazilian variant) as either a first-line vaccine or boost for already vaccinated people.

Earlier this week, Inovio reported positive data from Phase II part of the Phase II/III INNOVATE trial of its Covid-19 DNA vaccine INO-4800.