efdoralprin alfa (SAR447537) / Sanofi - LARVOL DELTA

Efdoralprin alfa vs plasma-derived alpha-1 antitrypsin augmentation therapy in adults with alpha-1 antitrypsin deficiency-associated emphysema: phase 2 ElevAATe trial (ERS 2026) - P2 | "Efdoralprin alfa significantly increased and maintained fAAT levels to and within the physiologically normal range of AATD-unaffected individuals, with less frequent dosing vs the weekly administered approved therapy."

Clinical • P2 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

A population pharmacokinetic/pharmacodynamic model for Efdoralprin Alfa and alpha‑1 proteinase inhibitor in adults with alpha-1 antitrypsin deficiency (AATD) emphysema (ERS 2026) - "PopPK/PD model accurately described the concentration-effect (fAAT) relationship for efdoralprin alfa."

Clinical • PK/PD data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

Delineating a reference interval for functional alpha-1 antitrypsin in the serum of healthy Pi*MM donors using an anti-neutrophil elastase capacity assay. (PubMed, Respir Res) - "The fAAT RI and LLN delineated by this study can be applied directly to clinical trials to evaluate the pharmacodynamic effect of AATD therapies, and, in conjunction with clinical trial pharmacokinetic data, can be used to support dosing decisions for patients with AATD."

Biomarker • Journal • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • ELANE

ELEVAATE OLE: Long-term, Open-label Study of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency Emphysema (clinicaltrials.gov) - P2 | N=185 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Efdoralprin Alfa vs. Plasma-derived Alpha-1 Proteinase Inhibitor (pdA1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema: Results From Phase 2 ElevAATe Trial (ATS 2026) - No abstract available

Clinical • P2 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

The European Medicines Agency (EMA) has granted orphan designation to efdoralprin alfa (SAR447537, formerly known as INBRX-101), an investigational recombinant human alpha-1 antitrypsin (AAT)-Fc fusion protein, for the potential treatment of alpha-1 antitrypsin deficiency (AATD) related emphysema, a rare respiratory condition with great unmet medical need. (GlobeNewswire) - "Efdoralprin alfa demonstrated superiority to a standard of care plasma-derived therapy in adults with AATD when dosed every three weeks (Q3W) or every four weeks (Q4W), meeting all primary and key secondary endpoints in the global phase 2 ElevAATe study (clinical study identifier: NCT05856331)."

Orphan drug • Alpha-1 Antitrypsin Deficiency

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

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

ELEVAATE OLE: Long-term, Open-label Study of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency Emphysema (clinicaltrials.gov) - P2 | N=185 | Recruiting | Sponsor: Sanofi | N=130 ➔ 185

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

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