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In a major rare disease deal, Sanofi is paying up to $2.2B acquiring Inhibrx Biosciences’ main asset, alpha-1 antitrypsin (AAT) treatment candidate INBRX-101. INBRX-101 is an optimized, recombinant AAT augmentation therapy currently in a registrational trial for AAT deficiency (“AATD”). 

AAT deficiency causes defective production of ATT, which protects the body from the neutrophil elastase enzyme. AATD is currently incurable and affects one in every 1500 to 3500 individuals of European ancestry. Along with Down syndrome and cystic fibrosis, it is one of the three most common, potentially terminal, rare diseases affecting people of European descent.

INBRX-101, Inhibrx says, is a precisely engineered recombinant human AAT-Fc fusion protein with the potential to:

  • Extend the dosing range from weekly to every three or four weeks, while maintaining patients in the normal range of AAT exposure.
  • Overcome challenges of maintaining the function of recombinant AAT, while manufacturing at commercial scale.
  • Maximize the functional activity of AAT, particularly in the lungs.
  • Complement RNAi approaches, while addressing all AATD patients.

There has, of course, been great interest in treating AATD with some type of gene therapy. Although it has been slow, there is noticeable progress here.

Researchers at Boston Medical Center and Boston University, for example, did a study using patient-derived liver cells (iHeps) that mimic the biology of liver hepatocytes, the main producers of alpha-1 antitrypsin protein in the body. The base editing technology corrected the Z mutation responsible for AATD and reduced the effects of the disease in the hepatocytes, demonstrating successful base editing in human cells.

“AATD is most commonly caused by the Z mutation, a single base substitution that leads to AAT protein misfolding and associated liver and lung disease. In this study, we apply adenine base editors to correct the Z mutation in patient-induced pluripotent stem cells (iPSCs) and iPSC-derived hepatocytes (iHeps),” wrote the investigators.

With all its drawbacks, gene therapy is not a sure fire bet, and alternative approaches, such as Inhibirex’s can see plenty of light at the end of the tunnel. 

All non-101 other assets including INBRX-105, INBRX-106, INBRX-109, Inhibrx’s non-101 discovery pipeline and its corporate infrastructure, will be spun into a new publicly traded company called Inhibrx Biosciences. Sanofi will acquire all outstanding shares of Inhibrx through a merger

The upfront cash portion of the consideration, if achieved, and the assumption of Inhibrx’s debt, implies an aggregate transaction value of approximately $2.2 billion. Additionally, Inhibrx shareholders will own 92% of New Inhibrx capitalized with $200 million in cash.

Following the closing, New Inhibrx will continue to operate under the “Inhibrx” name and will be led by Mark Lappe as Chairman and CEO, as well as the other members of the current management team of Inhibrx. New Inhibrx will continue to own Inhibrx’s other clinical therapeutic candidates, INBRX-105, INBRX-106, and INBRX-109, as well as its non-101 discovery pipeline and certain corporate infrastructure owned by Inhibrx.

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