Sanofi Announces First Acquisition Deal of 2024 to Strengthen Rare Disease Portfolio at $2.2 Billion

On January 23, Sanofi announced its first major acquisition deal of 2024, revealing a definitive agreement to acquire Inhibrx, Inc., a California-based clinical-stage biopharmaceutical company. This acquisition is poised to strengthen Sanofi’s position in the rare disease market, particularly with a focus on alpha-1 antitrypsin deficiency (AATD), a challenging inherited rare disease that primarily results in lung and liver damage. The aggregate amount of all payments involved may reach $2.2 billion and the transaction is slated to complete in Q2 2024.

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Understanding Alpha-1 Antitrypsin Deficiency

AATD is due to a mutation in the SERPINA1 gene that results in low serum levels of alpha-1 antitrypsin (AAT), a glycoprotein that acts as a neutrophil elastase inhibitor. AATD patients may be more susceptible to lung damage due to insufficient inhibition of elastase. Besides, AATD may lead to the accumulation of abnormal AAT proteins in the liver, resulting in liver damage (AATD-LD).

The disorder is relatively uncommon among those of Asian descent and more prevalent among individuals with European ancestry (about 1 in 1,500 to 3,500). In patients with AATD, respiratory symptoms may include shortness of breath (especially after exercise), wheezing, and chronic coughing with phlegm. They are also more likely to develop lung infections, chronic bronchitis, and emphysema. 

Approximately 15% of adult patients develop liver damage (AATD-LD), symptoms include itchy skin, jaundice and ascites. In extreme cases, patients may develop liver fibrosis and cirrhosis, which may necessitate a liver transplant to save their lives.

INBRX-101 – A Ray of Hope for AATD Patients

At the heart of this deal is INBRX-101, a human recombinant AAT developed by Inhibrx. As a drug for the augmentation therapy of AATD, INBRX-101 exhibits promise in allowing patients to normalize serum AAT levels through less frequent dosing, potentially improving the quality of life for affected individuals. The drug has completed a Phase 1 trial, demonstrating positive results in terms of safety and pharmacokinetics and is currently enrolling in a Phase 2 clinical trial to further evaluate the potential of INBRX-101 as a treatment for AATD.

Houman Ashrafian, Head of Research and Development at Sanofi, emphasized, “With our expertise in rare diseases and growing presence in immune-mediated respiratory conditions, INBRX-101 will complement our approach to deploy R&D efforts in key areas of focus and address the needs of the underserved AATD patients and communities.”

Transaction Terms and New Inhibrx’s Future

Under the terms of the agreement, Sanofi will acquire all outstanding shares of Inhibrx for $30.0 per share in cash, representing an equity value of approximately $1.7 billion. All assets other than INBRX-101, including Inhibrx’s immuno-oncology pipeline, will be spun off to form a new publicly traded company (New Inhibrx), with Sanofi retaining an 8% equity stake. Also, Inhibrx shareholders will receive a contingent value right (CVR) equal to $5, conditioned on the achievement of a regulatory milestone, together with 0.25 shares of New Inhibrx. In addition, Sanofi agrees to pay off Inhibrx’s outstanding debt balance and capitalize New Inhibrx with $200 million in cash. 

The aggregate amount of the above-mentioned payments may reach $2.2 billion. The transaction, unanimously approved by both Sanofi and Inhibrx Boards of Directors, is contingent upon the completion of the New Inhibrx spin-off and customary closing conditions, with an expected closing date in Q2 2024. Sanofi plans to finance the acquisition using available cash resources.

Competition Landscape of the Market for AATD Drugs

Sanofi’s buyout of Inhibrx marks not only its first acquisition in 2024, but also a significant step towards exploring the vast AATD treatment market. Upon entering the market, the French pharma giant may face competition from major drugmakers such as Takeda and Novo Nordisk.

These two big pharma companies take a different approach to AATD treatment, working on the development of RNA interference (RNAi) therapeutics that target the liver version of the disease (AATD-LD). Instead of incorporating the deficient protein, RNAi therapeutics are designed to reduce the production of mutant alpha-1 antitrypsin protein (Z-AAT). By reducing the accumulation of this inflammatory protein, it is believed that the therapy can halt the progression of liver disease and potentially allow the liver to regenerate and repair.

Take Takeda as an example, the Japanese company has been partnering with Arrowhead Pharmaceuticals to develop RNAi therapy for AATD-LD since October 2020. Their co-developed siRNA drug, named Fazirsiran, has completed the Phase 2 SEQUOIA trial with positive results and a Phase 3 trial already began in March 2023. 

Through a $3.3 billion acquisition of Dicerna Pharmaceuticals in November 2021, Novo Nordisk added Dicerna’s RNAi platform to its diversified research technology platforms. Their subcutaneously administered RNAi drug, called Belcesiran, is currently in a Phase 2 trial, which evaluates the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug in participants with AATD-LD.

Author

Richard Chau