Nrf2/Bach1 Program


vTv Therapeutics has identified multiple classes of novel non-electrophilic small molecules that can modulate/activate both NRF2 and Bach1 (the ARE transcriptional repressor) leading to potent activation of the NRF2 pathway.

In December 2020, we licensed worldwide rights to develop and commercialize clinical candidate HPP971 to Anteris Biopharma. Anteris intends to develop HPP971 for renal indications. vTv retains rights to all other program molecules outside of renal indications.

Clinical Trials

First generation compound, HPP971, has completed two phase 1 studies where it was well tolerated. 

Mechanism of Action

Activation of the NRF2 pathway not only relieves oxidative stress but also controls inflammatory responses, preventing tissue damage. To date, however, this approach has relied on molecules having reactive, electrophilic groups which may present safety and tolerability issues.

Modulation of the NRF2/Bach1 pathway by our compounds in vitro and in vivo shows suppression of both oxidative stress and inflammation by increasing anti-oxidant proteins, increasing cellular glutathione levels, increasing anti-inflammatory cytokine production, inhibiting NFκB transcriptional activity, and enhancing macrophages towards the anti-inflammatory “M2” phenotype.  

Published data suggest that small molecules that function as modulators of NRF2/Bach1 pathway may have therapeutic benefit in acute indications such as radiation protection in cancer patients, protection against contrast-induced renal injury, and prevention of ischemia/reperfusion injury, as well as a variety of chronic indications including respiratory injuries, neurodegenerative diseases, and mitochondrial myopathies.