Anteris Invests in Nrf2 Activator to Combat Renal Disease

North Carolina-based vTv Therapeutics has provided worldwide rights for its novel clinical-stage Nrf2 activator compound, HPP971, to newly formed Anteris Bio, a biotech investment firm that will further develop HPP971 as a new treatment for renal disease.

Chronic kidney disease (CKD) represents an area of interest for Anteris Bio, particularly in regard to HPP971. Across the globe, CKD is a leading cause of morbidity and mortality. Up to 700 million people worldwide are diagnosed with CKD, which is directly responsible for more than 1 million deaths per year. There exists a significant unmet need for renal disease, as many standard treatments focus on the management of symptoms, rather than the underlying mechanisms involved in disease pathogenesis.

HPP971 is an advanced oral, small molecule activator of the Nrf2 pathway (nuclear factor erythroid 2-related factor 2) developed by vTv Therapeutics and included in the company’s portfolio of Nrf2 compounds. The Nrf2 activator, which will be renamed to ANT-401 following the finalization of the licensing agreement, features a mechanism that has the ability to modify disease across several etiologies of renal disease. 

Nrf2, a transcription factor, is required for expression of numerous antioxidant genes regulated by the ARE promoter sequence. ANT-401 is an activator of Nrf2 via inhibition of Bach1, a transcription repressor capable of preventing Nrf2 activity in the nucleus. Bach1 inhibition through NRF2 pathway activation may combat oxidative stress and control inflammation, thereby preventing damage to tissues.

“The Nrf2 pathway is a promising, novel target for combating many diseases related to oxidative stress, including renal disease,” according to a statement made by Steve Holcombe, President and Chief Executive Officer of vTv Therapeutics. “We’re thrilled to partner with Anteris Bio to further the development of HPP971. With a focus in renal disease and a strategic partnership with TrialSpark, they will have the ability to efficiently develop HPP971 to ultimately bring a potential new treatment option to patients suffering from kidney disease.”

To date, HPP971 has undergone and completed two Phase I studies which support the tolerability of the compound.

According to the terms of the licensing deal, Anteris Bio will give an upfront payment of $2 million to vTv Therapeutics in exchange for the rights to develop and commercialize HPP971. vTv Therapeutics will also be eligible to receive up to $151 million in milestone payments, in addition to low double-digit royalties on annual net sales. vTv Therapeutics says it will also receive a minority equity interest in Anteris Bio according to terms in the agreement.

Following the announcement of the licensing agreement with Anteris Bio, vTv Therapeutics (NASDAQ:VTVT) gained 11% premarket in shares. 

vTv Therapeutics’ other promising oral, small molecule, liver selective glucokinase activator TTP399 recently showed promise in a Phase II trial for type I diabetes. Treatment with the investigational compound in this study was not associated with an increased risk of diabetic ketoacidosis (DKA) and lead to significant improvements in HbA1c. In addition, the compound was associated with reductions in bolus insulin dose but no corresponding increase in the risk of hypoglycemia or DKA.