Sanofi Acquires INBRX-101 Pipeline for $2.2 Billion to Advance Treatment for Alpha-1 Antitrypsin Deficiency

Today, Inhibrx and Sanofi announced that the two companies have entered into a definitive agreement, under which Aventis, a subsidiary of Sanofi located in Pennsylvania, will acquire all assets and liabilities related to INBRX-101.

INBRX-101 is a recombinant alpha-1 antitrypsin (“AAT”) augmentation therapy currently in registrational trials for the treatment of alpha-1 antiprotease deficiency (“AATD”). Prior to the completion of the merger, all non-INBRX-101 assets and liabilities, including INBRX-105, INBRX-106, INBRX-109, Inhibrx’s non-INBRX-101 discovery pipeline, and its corporate infrastructure, will be spun off into a new public company, Inhibrix Biosciences (“new Inhibrx”).

Under the terms of the agreement, Sanofi will acquire all outstanding shares of Inhibrx through a merger. Each Inhibrx shareholder will receive: (i) $30.00 in cash per share, (ii) one contingent value right per share, representing the right to receive a $5.00 cash contingent payment upon the achievement of regulatory milestones, and for every four shares of Inhibrx common stock held, a share in New Inhibrx. Additionally, as part of the transaction, Sanofi will assume and repay Inhibrx’s outstanding third-party debt, fund New Inhibrx with $200 million in cash, and retain an 8% equity stake. The boards of both Inhibrx and Sanofi have unanimously approved the transaction.

In aggregate, the upfront cash portion, potential contingent value payments (if realized), and the assumption of Inhibrx debt imply a total transaction value of approximately $2.2 billion (equivalent to RMB 15.8 billion). Additionally, shareholders of Inhibrx will own 92% of the new Inhibrix, capitalized with $200 million in cash.

Alpha-1 Antitrypsin Deficiency, also known as AATD, is a hereditary rare disease with approximately 100,000 patients in the United States. AATD is characterized by insufficient levels of AAT protein, leading to lung tissue damage, loss of lung function, and reduced life expectancy.

Plasma-derived AAT infusion is currently the standard treatment regimen, but it cannot maintain the AAT concentration within the normal range in patients and requires once-weekly intravenous administration, which is frequent and inconvenient. Moreover, this regimen relies on plasma collection, which may lead to unsustainable situations.

INBRX-101 is an engineered recombinant human alpha-1 antitrypsin (AAT)-Fc fusion protein developed by Inhibrx Biosciences, Inc., for the treatment of emphysema in patients with alpha-1 antitrypsin deficiency (AATD).

INBRX-101 is designed to safely achieve and maintain AAT protein levels found in healthy individuals, with a favorable safety profile and the convenience of once-monthly dosing. It is supported by Phase 1 multi-dose escalation study data. The study demonstrated that INBRX-101, administered intravenously every three weeks at doses of 40, 80, and 120 mg/kg, leads to the expected accumulation of functional AAT levels and shows the ability to achieve fully normalized functional AAT levels in patients with severe AATD.

In addition, pharmacokinetic models suggest that accumulation may continue with subsequent doses. Steady state is expected to be reached after approximately 5 to 6 consecutive doses administered once every 3 or 4 weeks.

INBRX-101 was well-tolerated, with no serious or severe adverse events reported. Most drug-related adverse events were mild. Moreover, moderate drug-related adverse events were transient and reversible.

In a randomized, controlled, double-blind, head-to-head superiority study named ElevAATe (NCT05856331), INBRX-101 is being compared to plasma-derived AAT. The primary endpoint is the mean change in average functional AAT concentration from baseline to steady-state mean serum trough fAAT concentration, as measured by anti-neutrophil elastase capacity.

In March 2022, INBRX-101 was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA). Compared with the weekly infusion interval of available plasma-derived AAT therapies, its advantage lies in potentially requiring fewer infusion intervals.

Inhibrx CEO Mark Lappe once stated, "The orphan drug designation reflects the FDA's acknowledgment of the significant unmet need for novel therapies in this patient population, especially given the lack of improvements in standard treatments over recent decades. We believe INBRX-101 has the potential to greatly enhance the quality of life for patients with AATD and look forward to collaborating closely with regulators, experts, patients, and their families to achieve this goal."

In June 2023, INBRX-101 received FDA Fast Track designation again. Inhibrx has previously stated that initial data from the ElevAATe trial is expected to be disclosed by the end of 2024.

Inhibrx is a biotechnology company with a rich pipeline of products. The company combines a deep understanding of target biology with innovative protein engineering, proprietary discovery technologies, and an integrated approach to research and development to design highly differentiated therapeutic candidates, at the core of which is the company's proprietary single-domain antibody (sdAb) platform.

Inhibrx Biosciences, Inc. has established an innovative single-domain antibody (sdAb) platform based on the continuous improvement of traditional monoclonal antibodies (mAb) and fusion proteins. This platform has developed best-in-class drugs that break the limitations of traditional therapies and effectively address complex biological challenges.

Based on the sdAb platform, the company has developed a rich product pipeline, with four projects currently in clinical trials, focusing on fields such as oncology, infectious diseases, and rare diseases.

In addition to INBRX-101 involved in this transaction, Inhibrx Biosciences, Inc. has three oncology projects in the clinical stage.

Among them, INBRX-109 is a novel tetravalent DR5 agonist. A single molecule can bind to four receptors, significantly enhancing the DR5 agonistic effect and leading to tumor cell death. INBRX-109 is currently in Phase II clinical trials in the United States.

INBRX-105 is a first-class, tetravalent bispecific antibody. It contains four binding domains, two of which target PD-L1 and the other two target 4-1BB. However, its molecular weight is only two-thirds that of a conventional antibody. Based on the biological characteristic of high PD-L1 expression in the tumor microenvironment, combined with unique design through antibody engineering, INBRX-105 can effectively and continuously block PD-L1 while conditionally activating 4-1BB in the tumor microenvironment. This combination of "removing the brakes" and "stepping on the accelerator" not only greatly enhances the drug's efficacy but also avoids the toxicity associated with 4-1BB monotherapy, addressing the challenges faced by similar monoclonal antibody drugs during clinical development.

INBRX-106 is a hexavalent antibody targeting OX40 activation, demonstrating enhanced immune activation capabilities and effectively activating the OX40 pathway even without exogenous crosslinking. In preclinical animal tumor models, INBRX-106 exhibited robust monotherapy antitumor efficacy and favorable synergy with PD-1.

It is reported that Sanofi is expected to fund this transaction using existing cash resources. Sanofi's acquisition of Inhibrx is contingent upon the completion of the new Inhibrix spin-off transaction and other customary closing conditions, including regulatory approvals and approval from Inhibrx shareholders. Provided that customary closing conditions are satisfied or waived, Sanofi and Inhibrx anticipate the transaction will close in the second quarter of 2024.

After the handover, New Inhibrx will continue to operate under the name "Inhibrx" and be led by Chairman and Chief Executive Officer Mark Lappe, along with other members of Inhibrx's current management team. New Inhibrx will continue to own Inhibrx’s other clinical candidate therapeutic drugs INBRX-105, INBRX-106, and INBRX-109, as well as its non-101 discovery pipeline and certain corporate infrastructure owned by Inhibrx.