Inhibrx, Inc. (NASDAQ:INBX) is a clinical-stage biopharmaceutical company that is making significant strides in the development of novel biologic therapeutic candidates. With a focus on oncology and orphan diseases, the company has built an impressive pipeline of therapeutic candidates that leverage its proprietary modular protein engineering platforms.

Business Overview

Inhibrx's core strategy is to leverage its innovative protein engineering technologies and deep understanding of target biology to create therapeutic candidates with attributes and mechanisms superior to current approaches. The company's pipeline includes several promising candidates, including INBRX-101, an optimized, recombinant alpha-1 antitrypsin (AAT) augmentation therapy for the treatment of alpha-1 antitrypsin deficiency (AATD), INBRX-109, a tetravalent death receptor 5 (DR5) agonist for the treatment of difficult-to-treat cancers, and INBRX-106, a precisely engineered hexavalent agonist targeting OX40 for the treatment of locally advanced or metastatic solid tumors.

Financials

Inhibrx's financial performance has been marked by significant investments in research and development to advance its pipeline. In the fiscal year ended December 31, 2023, the company reported annual revenue of $1.8 million, annual net loss of $241.4 million, annual operating cash flow of -$193.3 million, and annual free cash flow of -$197.9 million.

In the first quarter of 2024, the company reported total revenue of $0 million, a net loss of $78.7 million, and used $63.1 million in operating cash flow. The company's research and development expenses increased by 71% to $63.9 million in the first quarter of 2024, compared to $37.4 million in the same period of the prior year, reflecting the company's continued investment in its pipeline.

Liquidity

As of March 31, 2024, Inhibrx had $252.5 million in cash and cash equivalents, which the company believes will be sufficient to fund its operations for at least the next 12 months. The company has also secured $200.0 million in gross principal outstanding in term loans under its Amended 2020 Loan Agreement with Oxford Finance LLC, which matures in January 2027.

Inhibrx's future liquidity and capital funding requirements will depend on numerous factors, including the outcome and costs of its ongoing and future clinical trials, the timing of regulatory approvals, and the commercialization of its therapeutic candidates, if approved.

INBRX-101: Advancing Towards Regulatory Approval for AATD

Inhibrx's lead therapeutic candidate, INBRX-101, is an optimized, recombinant AAT augmentation therapy for the treatment of AATD. In March 2022, the FDA granted orphan drug designation for INBRX-101, and in May 2023, the FDA granted Fast Track designation for the treatment of patients with emphysema due to AATD.

In May 2022, Inhibrx announced positive topline results from the Phase 1 clinical trial of INBRX-101, which demonstrated the potential to achieve normal AAT levels with less frequent dosing than the current standard of care, and showed the treatment was well tolerated with no drug-related severe or serious adverse events at doses up to and including 120 mg/kg in single and multi-dose administered intravenously.

In April 2023, the company initiated the ElevAATe registration-enabling trial for INBRX-101 for the treatment of patients with emphysema due to AATD. The primary endpoint of the trial is the mean change in the average functional AAT (fAAT) concentration as measured by anti-neutrophil elastase capacity from baseline to average serum trough fAAT concentration at steady state. The initial read-out from the ElevAATe trial is expected in mid-2025, and Inhibrx intends to submit for regulatory approval once the trial is completed.

INBRX-109: Promising Results in Difficult-to-Treat Cancers

Inhibrx's most advanced therapeutic candidate, INBRX-109, is a tetravalent DR5 agonist currently being evaluated in patients diagnosed with difficult-to-treat cancers, such as chondrosarcoma, mesothelioma, colorectal cancer, Ewing sarcoma, and pancreatic adenocarcinoma.

In June 2021, based on the initial Phase 1 data results, Inhibrx initiated a registration-enabling Phase 2 trial for the treatment of unresectable or metastatic conventional chondrosarcoma, for which the FDA and the European Medicines Agency (EMA) granted orphan drug designation in November 2021 and August 2022, respectively.

In November 2022, the company announced updated efficacy and safety data from the ongoing Phase 1 INBRX-109 expansion cohorts for the treatment of chondrosarcoma, which showed disease control was observed in patients with and without isocitrate dehydrogenase (IDH) mutations. Of the 210 patients studied to date, the treatment-related serious adverse events observed were primarily related to abnormal laboratory findings, gastrointestinal disorders, blood and lymphatic system disorders, and hepatobiliary disorders.

On November 2, 2023, Inhibrx announced preliminary efficacy and safety data from the Phase 1 trial of INBRX-109 in combination with Irinotecan and Temozolomide for the treatment of advanced or metastatic, unresectable Ewing sarcoma. Among the 13 patients evaluable as of the data cut of September 8, 2023, the observed disease control rate was 76.9%, with 7 patients achieving partial responses (53.8%) and 3 patients achieving stable disease (23.1%). The combination of INBRX-109 with Irinotecan and Temozolomide was well tolerated from a safety perspective.

INBRX-106: Exploring the Potential of OX40 Agonism

INBRX-106 is a precisely engineered hexavalent single-domain antibody (sdAb)-based therapeutic candidate targeting OX40, designed to be an optimized agonist of this co-stimulatory receptor. It is currently being investigated as a single agent and in combination with Keytruda in patients with locally advanced or metastatic solid tumors.

Parts 1 and 3 of the Phase 1/2 clinical trial, which involved dose escalation as a single agent and in combination with Keytruda, have been completed. Inhibrx observed durable responses across multiple tumor types. To date, of the 166 patients studied, the treatment-related serious adverse events observed were primarily related to general disorders, metabolism and nutrition disorders, gastrointestinal disorders, blood and lymphatic system disorders, cardiac disorders, and other miscellaneous events.

The company has expanded the enrollment for Part 2, the single agent dose expansion, to increase the dataset in the single agent cohorts and to enroll additional non-small cell lung cancer (NSCLC) patients. Inhibrx expects to announce additional data from Part 2 in 2025. The company continues to enroll patients with NSCLC and head and neck squamous cell carcinoma (HNSCC) in Part 4, the combination expansion cohorts, and plans to initiate at least one additional cohort by mid 2024. Inhibrx expects to have a more mature dataset during the third quarter of 2025 and plans to provide an update at that time.

Recent Developments

Proposed Acquisition by Sanofi

In January 2024, Inhibrx announced that it had entered into an Agreement and Plan of Merger with Aventis, a wholly owned indirect subsidiary of Sanofi, whereby Sanofi will indirectly acquire, through Aventis, all the assets and liabilities primarily related to INBRX-101. Immediately prior to the closing of the proposed merger, all assets and liabilities not primarily related to INBRX-101 will be spun out into a new publicly traded company, New Inhibrx.

Under the terms of the Merger Agreement, Aventis will acquire all of Inhibrx's outstanding shares through the merger, and in turn, each Inhibrx shareholder will receive: (i) $30.00 per share in cash, (ii) one contingent value right per share, representing the right to receive a contingent payment of $5.00 in cash upon the achievement of a regulatory milestone, and (iii) one SEC-registered, publicly listed, share of New Inhibrx for every four shares of Inhibrx common stock held.

The boards of directors of both Inhibrx and Sanofi have unanimously approved the spin-off and the merger. Sanofi's acquisition of Inhibrx is subject to the completion of the New Inhibrx spin-off transaction and other customary closing conditions, including approval by Inhibrx's shareholders. The companies expect the transaction to close in the second quarter of 2024.

Risks and Challenges

Inhibrx faces several risks and challenges common to the biopharmaceutical industry, including the inherent uncertainty of clinical development, the potential for regulatory delays or denials, and the need to secure additional funding to support its ongoing operations and pipeline development. The company's reliance on third-party contract research organizations and contract manufacturing organizations also exposes it to operational and supply chain risks.

Additionally, the proposed acquisition by Sanofi and the related spin-off of New Inhibrx introduce transaction-specific risks, such as the potential for the merger to not be completed, the successful separation and capitalization of New Inhibrx, and the integration of INBRX-101 into Sanofi's operations.

Conclusion

Inhibrx is a promising biopharmaceutical company with a robust pipeline of novel biologic therapeutic candidates targeting oncology and orphan diseases. The company's lead candidate, INBRX-101, has shown promising results in the treatment of AATD, and its most advanced candidate, INBRX-109, is demonstrating efficacy in difficult-to-treat cancers. The proposed acquisition by Sanofi and the spin-off of New Inhibrx present both opportunities and risks for the company and its shareholders.

As Inhibrx continues to advance its pipeline and navigate the regulatory landscape, investors will be closely watching the progress of its clinical trials, the outcome of the proposed transaction, and the company's ability to secure the necessary funding to support its long-term growth. With its innovative technology platforms, experienced management team, and promising therapeutic candidates, Inhibrx remains a company to watch in the biopharmaceutical industry.