SAR447537 / Sanofi - LARVOL DELTA

ELEVAATE: Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

ELEVAATE OLE: Open Label Extension Study of INBRX-101 in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Sep 2028 | Trial primary completion date: Sep 2027 ➔ Jun 2028

Enrollment open • Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Sanofi | Trial completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

Press Release: Sanofi completes acquisition of Inhibrx, Inc. (GlobeNewswire) - "Sanofi announced today the completion of its acquisition of Inhibrx, Inc...The acquisition adds SAR447537 (formerly INBRX-101) to Sanofi’s rare disease pipeline, underscoring the company’s commitment to pursuing differentiated and potential best-in-class medicines that build upon our existing strengths and capabilities...The former holders of shares of Inhibrx common stock voted to approve the acquisition at a special meeting of stockholders on May 24, 2024. Upon the closing of the acquisition, former shareholders of Inhibrx became entitled to receive $30.00 per share in cash, which represents a total equity value of approximately $1.7 billion (on a fully diluted basis), as well as one contingent value right per share to receive $5.00 upon the achievement of a regulatory milestone....'Inhibrx Biosciences, which was a wholly owned subsidiary of Inhibrx prior to the distribution, acquired all of the assets of Inhibrx not related to SAR447537, which include INBRX-109 and INBRX-106...'"

M&A • Alpha-1 Antitrypsin Deficiency • Oncology • Rare Diseases • Solid Tumor

Inhibrx Inc. Stockholders Approve Sale of INBRX-101 to Sanofi (PRNewswire) - " Inhibrx...announced that, at a special meeting (the 'Special Meeting'), the Company's stockholders approved the sale to Sanofi of all the assets and liabilities primarily related to INBRX-101, an optimized, recombinant alpha-1 antitrypsin ('AAT') augmentation therapy currently in a registrational trial for the treatment of patients with alpha-1 antitrypsin deficiency ('AATD'). Immediately prior to the closing of the merger, all non-101 assets and liabilities, including INBRX-105, INBRX-106, INBRX-109, Inhibrx's non-101 discovery pipeline and its corporate infrastructure, will be spun out from the Company into a new publicly traded company, Inhibrx Biosciences, Inc. ('New Inhibrx')."

Commercial • Alpha-1 Antitrypsin Deficiency • Solid Tumor

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency: A Phase 1 Study. (PubMed, Chronic Obstr Pulm Dis) - "PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM). The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101."

Journal • P1 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Protease Inhibitory Specificity Profile of the Recombinant Human Alpha-1 Antitrypsin (AAT)-Fc Fusion Protein INBRX-101 (ATS 2024) - P1, P2 | "INBRX-101 is a recombinant, next-generation human AAT-Fc fusion protein containing 2 AAT molecules that has been optimized to have a longer half-life and achieve higher serum AAT levels than pdAAT... Consistent with the physiological activity of wild-type AAT, INBRX-101 specifically inhibited the proteases NE and PR3, both of which have a recognized role in the pathology of AATD. Modifications to extend the half-life of INBRX-101 did not lead to off-target activity against thrombin or trypsin. INBRX-101 is currently being evaluated in ElevAATe (NCT05856331), a registration-enabling phase 2 randomized trial in patients with AATD that will compare INBRX-101 vs pdAAT and their impact on functional AAT levels."

Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hematological Disorders • ELANE

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Inhibrx, Inc. | Trial completion date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Nov 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

ELEVAATE OLE: Open Label Extension Study of INBRX-101 in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Inhibrx, Inc. | Initiation date: Jan 2024 ➔ Jun 2024

Trial initiation date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Inhibrx Announces Sale of INBRX-101 to Sanofi for an aggregate value of up to $2.2B (PRNewswire) - "Inhibrx, Inc...and Sanofi...today announced that the companies have entered into a definitive agreement under which Aventis Inc., a Pennsylvania corporation (a subsidiary of Sanofi) will acquire all the assets and liabilities associated with INBRX-101, an optimized, recombinant alpha-1 antitrypsin ('AAT') augmentation therapy currently in a registrational trial for the treatment of patients with alpha-1 antitrypsin deficiency ('AATD'). Immediately prior to the closing of the merger, all non-101 assets and liabilities, including INBRX-105, INBRX-106, INBRX-109, Inhibrx's non-101 discovery pipeline and its corporate infrastructure, will be spun out from the Company into a new publicly traded company, Inhibrx Biosciences, Inc. ('New Inhibrx')....New Inhibrx will continue to own Inhibrx's other clinical therapeutic candidates, INBRX-105, INBRX-106, and INBRX-109..."

Commercial • Licensing / partnership • Alpha-1 Antitrypsin Deficiency • Immunology • Oncology • Solid Tumor

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Inhibrx, Inc.

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

Inhibrx Reports Third Quarter 2023 Financial Results and Recent Corporate Highlights (PRNewswire) - "...the Company's payments to its contract research organizations, or CRO, partners continue to increase as the registration-enabling Phase 2 trials progress for both INBRX-101 for the treatment of emphysema due to AATD and INBRX-109 for the treatment of unresectable or metastatic conventional chondrosarcoma, and additional cash outlay to its CRO partners for the INBRX-105 and INBRX-106 Phase 1/2 trials...Research and development expenses were $38.1 million during the third quarter of 2023, compared to $24.9 million during the third quarter of 2022...an increase in clinical trial expenses, primarily related to the registration-enabling Phase 2 trial for INBRX-101 for the treatment of emphysema due to AATD, which was initiated during the current year, as well as the progression of its INBRX-109 registration-enabling Phase 2 trial for the treatment of unresectable or metastatic conventional chondrosarcoma."

Commercial • Alpha-1 Antitrypsin Deficiency • Head and Neck Cancer • Immunology • Oncology • Sarcoma • Solid Tumor

Late Breaking Abstract - Validation of assays measuring functional alpha-1 antitrypsin (AAT) in patients with AAT deficiency (AATD) (ERS 2023) - "This validated ANEC assay addresses the unique challenges associated with measuring fAAT in BALF and sera, making it well suited for evaluating biochemical efficacy of novel AATD therapies (eg, INBRX-101) in registrational clinical trials.; Pulmonary function testing; Physiology; Imaging; Endoscopy and interventional pulmonology; Surgery; Cell and molecular biology; General respiratory patient care; Epidemiology"

Clinical • Late-breaking abstract • Alpha-1 Antitrypsin Deficiency • Pulmonary Disease • Respiratory Diseases • ELANE

ELEVAATE OLE: Open Label Extension Study of INBRX-101 in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Inhibrx, Inc.

New P2 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

INBRX-101: “INBRX-101 was well tolerated in this completed phase 1 study, with a safety profile consistent with those of approved pdAAT augmentation therapies”; Alpha-1 antitrypsin deficiency (Inhibrx) - ATS 2023: “The 80- and 120-mg/kg Q3W doses of INBRX-101 maintained serum functional AAT levels above the lower limit of normal throughout the dosing period”

P1 data • Alpha-1 Antitrypsin Deficiency

Inhibrx Granted Fast Track Designation for INBRX-101 for the Treatment of Alpha-1 Antitrypsin Deficiency (PRNewswire) - "Inhibrx...announced today that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to INBRX-101, an optimized recombinant human AAT-Fc fusion protein, for the treatment of patients with emphysema due to alpha-1 antitrypsin deficiency (AATD)....The ElevAATe study (NCT05856331) is a registration-enabling trial for INBRX-101 initiated in April 2023 and is designed as a randomized, controlled, double-blind, head-to-head superiority study examining INBRX-101 against plasma-derived AAT....The initial read-out from the ElevAATe trial is expected to occur in late 2024."

Fast track designation • P2 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Graft versus Host Disease • Immunology

Recombinant Human Alpha-1 Antitrypsin (AAT) Protein INBRX-101 Demonstrates Potential to Achieve Lung Penetration and Normal Functional Serum AAT Levels in Patients With AAT Deficiency (ATS 2023) - P1 | "At day 56 post dose, INBRX-101 was present in all assessed lung lobes from all 11 patients sampled.Conclusions INBRX-101 80 and 120 mg/kg q3w maintain serum functional AAT levels above the lower limit of normal throughout the dosing period; at both doses, INBRX-101 was detected in BALF. Inhibrx plans to initiate a pivotal study exploring extended-interval dosing of INBRX-101 in 2023."

Clinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Inhibrx, Inc.

New P2 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

Inhibrx Reports Fourth Quarter and Fiscal Year 2022 Financial Results (PRNewswire) - "INBRX-101....We expect to initiate clinical trial(s) in Graft versus host disease, or GvHD, during the second half of 2023."

New trial • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease

"$INBX Inhibrx To Host Webcast to Announce Regulatory Pathway for INBRX-101, its Optimized Recombinant Human AAT-Fc Protein for the Treatment of Alpha-1 Antitrypsin Deficiency https://t.co/pmA71KrEJn" (@stock_titan)

Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Inhibrx, Inc. | Recruiting ➔ Completed

Trial completion • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Recombinant AAT-Fc fusion protein INBRX-101 achieves normal serum AAT levels in patients with alpha-1 antitrypsin deficiency (AATD) (ERS 2022) - P1 | "Trough levels of functional AAT exceeded those achieved by current pdAAT therapies. INBRX-101 maintains normal AAT serum levels (>20 µM) with every 3-wk dosing, with potential for longer intervals."

Clinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

INBRX-101: A Novel Recombinant AAT-Fc Fusion Protein That Achieves Normal Serum AAT Levels with Extended Interval Dosing for Patients with Alpha-1 Antitrypsin Deficiency (ATS 2022) - P1 | "Observed trough levels of functional AAT exceeded those reported historically for pdAAT.Additional patients, updated safety, PK, PD biomarker, and immunogenicity data from the multiple dose cohort will be presented.CONCLUSIONS INBRX-101 is the first augmentation therapy to achieve and maintain normal AAT serum levels above 20 µM and with every three-week or potentially longer dosing intervals. Further studies of INBRX-101 in AATD patients are planned."

Clinical • Late-breaking abstract • Alpha-1 Antitrypsin Deficiency • Dermatology • Fatigue • Genetic Disorders • Hepatology • Pruritus • Pulmonary Disease • Respiratory Diseases • Urticaria

Evaluation of Safety and Pharmacokinetics of the Recombinant Human AAT-Fc Fusion Protein INBRX-101 in Patients with Alpha-1 Antitrypsin Deficiency (ATS 2022) - P1 | "Observed trough levels of functional AAT exceeded those reported historically for plasma-derived AAT. The study is ongoing and updated safety, PK, PD biomarker and immunogenicity data from all parts and cohorts will be presented.ConclusionINBRX-101 is generally safe and well-tolerated and has shown the potential to maintain normal AAT serum levels, >20 µM, over the entire dosing interval on a dosing schedule of every three weeks with potential for once-monthly dosing."

Clinical • PK/PD data • Alpha-1 Antitrypsin Deficiency • Dermatology • Fatigue • Genetic Disorders • Hepatology • Hypertension • Pruritus • Pulmonary Disease • Respiratory Diseases • Urticaria

Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Inhibrx, Inc. | Trial completion date: Jul 2022 ➔ Nov 2022 | Trial primary completion date: Apr 2022 ➔ Aug 2022

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases