AI Drug Discovery for Pharma and Biotech

Drug discovery

42

drugs

With orphan designations

Overview

Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels/functionality of alpha-1 antitrypsin (AAT). This deficiency results in unopposed neutrophil elastase activity, causing early-onset emphysema (often misdiagnosed as COPD) and liver disease (cirrhosis, hepatocellular carcinoma). Smoking accelerates pulmonary damage. Diagnosis involves serum AAT quantification and genotyping. Management includes smoking cessation, augmentation therapy, and liver/lung transplantation for advanced disease [1][2][16].

Population

  • Prevalence: 1 in 1,500–3,500 individuals of European ancestry; severe deficiency (Pi*ZZ genotype) affects 70,000–100,000 in the US, with >90% undiagnosed [1][12]

  • Highest risk: Northern European and Iberian descent; rare in Asian populations [1][7]

  • Carriers (Pi*MZ/MS) have variable risk of lung/liver disease, especially with smoking [2][12]

Burden

  • Mortality: 4.7x higher vs general population; pediatric liver disease carries 33.8x mortality risk [9][14]

  • Morbidity: 32% develop COPD, 21% emphysema, 12% bronchiectasis; 10–15% develop cirrhosis [12][19]

  • Socioeconomic impact: High healthcare costs, frequent exacerbations requiring hospitalization (~1.5/year), and caregiver stress due to progressive disability [4][5][19]

Therapies

  • Augmentation therapy: Weekly IV AAT infusions (Prolastin-C®, Aralast NP™, Zemaira®) to slow emphysema progression [3][16][18]

  • COPD management: Bronchodilators, inhaled corticosteroids, pulmonary rehabilitation, and oxygen therapy [8][18]

  • Liver transplant: Curative for liver failure; investigational approaches include gene therapy and hepatocyte transplantation [8][16]

Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare renal diseases, rare respiratory diseases, rare transplant-related disorders

Research Papers

1,034 drug discovery papers about Alpha-1-antitrypsin deficiency, with 1 first-in-class and 33 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

1,034 drug discovery papers about Alpha-1-antitrypsin deficiency, with 1 first-in-class and 33 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

2026-08-08 | p62/SQSTM1-KEAP1 complex prevents clearance of ubiquitinated Z alpha-1 antitrypsin and aggravates liver proteotoxicity.

Liver disease in Alpha-1 antitrypsin deficiency (AATD) is caused by the toxic accumulation of mutant Z alpha-1 antitrypsin (Z-AAT) within the endoplasmic reticulum (ER) of hepatocytes. Livers from PiZ transgenic mice expressing the human Z-AAT and AATD patients were both found to have increased p62/SQSTM1, a multifunctional protein involved in protein homeostasis, consistent with previous reports. However, whether p62/SQSTM1 is a marker of Z-AAT globules or plays an active role in Z-AAT proteostasis is unclear. The goal of this study was to elucidate the involvement of p62/SQSTM1 in the formation of Z-AAT globules that are responsible for liver injury in AATD. In the present study, we found that p62/SQSTM1 decorated ubiquitin-positive, Periodic-Acid Shiff-diastase-resistant Z-AAT globules and interacted with Z-AAT at the ER-cytosol interface. Genetic ablation of p62/SQSTM1 in PiZ mice (PiZ;p62-/-) led to marked reduction in hepatic Z-AAT globules and polymers, and decreased serum Z-AAT, highlighting a central role for p62/SQSTM1 in disease pathogenesis. Moreover, hepatocyte-specific somatic deletion of the ubiquitin-association (UBA) domain of p62/SQSTM1 reduced Z-AAT aggregation. Furthermore, KEAP1 was identified as a binding partner of p62/SQSTM1-Z-AAT complex, leading to nuclear translocation and activation of NRF2. Inhibition of KEAP1-p62/SQSTM1 interaction reduced the abundance of p62 and phosphorylated p62, decreased intracellular Z-AAT, and redistributed NRF2 to the cytoplasm. In conclusion, this study identifies p62/SQSTM1 as a regulator of Z-AAT proteostasis and link Z-AAT/p62 accumulation to KEAP1 sequestration and NRF2 pathway activation in liver disease due to Z-AAT.

Open article ↗



2026-07-29 | From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases.

Rare genetic liver diseases collectively affect millions of individuals worldwide and encompass a heterogeneous group of monogenic disorders including Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, urea cycle disorders, progressive familial intrahepatic cholestasis, and acute hepatic porphyrias. While conventional management relies on dietary modification, pharmacotherapy, and ultimately liver transplantation, the advent of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has opened transformative therapeutic avenues. This review provides a comprehensive and critical appraisal of the current landscape of CRISPR-based therapies for genetic liver diseases, from preclinical proof-of-concept studies to landmark clinical trials. We examine the evolution from conventional Cas9 nuclease-mediated editing to precision tools including base editors and prime editors, which enable single-nucleotide corrections without inducing double-strand DNA breaks. The role of lipid nanoparticle delivery systems in achieving efficient hepatocyte-targeted delivery is discussed, alongside emerging challenges in pediatric dosing and immunogenicity. We highlight the paradigm shift toward personalized, patient-specific CRISPR therapies, exemplified by the first-in-human bespoke gene editing treatment delivered in 2025. Competing nucleic acid technologies, including RNA interference and antisense oligonucleotides, are compared in terms of durability, safety, and cost-effectiveness. Finally, we critically evaluate the evolving regulatory landscape and propose a priority framework for selecting genetic liver diseases most amenable to CRISPR-based correction. This review underscores that CRISPR gene editing is transitioning from experimental promise to clinical reality for genetic liver diseases, with personalized approaches poised to redefine the treatment paradigm.

Open article ↗



2026-06-01 | B101-10 RNA Editing for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)

Abstract Rationale Severe AATD is commonly caused by homozygous mutations in the SERPINA1 gene (Pi*ZZ), resulting in misfolded Z-AAT protein in the liver and offering decreased protection for the lung against neutrophil elastase. Current standard of care focuses on augmenting serum AAT levels through weekly infusions of human plasma-purified AAT to maintain serum levels above a putative protective threshold (11 µM). Liver disease is not addressed by this intervention. WVE-006, an investigational N-Acetylgalactosamine-conjugated RNA editing oligonucleotide, is designed to recruit endogenous ADAR enzymes to edit SERPINA1 mRNA in hepatocytes, replacing Z-AAT with M-AAT synthesis. This approach aims to increase serum M-AAT levels while reducing Z-AAT, preserve endogenous regulation of AAT expression, and address both lung and liver manifestations of severe AATD. Methods RestorAATion-2 (NCT06405633) is an ongoing phase 1b/2a clinical trial evaluating the safety, tolerability, pharmacodynamics, and pharmacokinetics of single- and multiple-ascending doses of WVE-006 (200, 400, 600 mg; n = 8 per cohort) in individuals with a ZZ genotype. Participants received a single subcutaneous dose of WVE-006 with a 12-week observation period, followed by biweekly (200 mg) or monthly doses (400, 600 mg) for 12 weeks, with a subsequent 12-week observation period. Serum levels of M-AAT, Z-AAT and total (M + Z) AAT were measured by LC-MS/MS assays, while functional AAT levels were assessed by a neutrophil elastase inhibition assay. Results In the 200 mg multidose cohort, mean maximum serum M-AAT levels reached 7.2 μM in ZZ individuals, corresponding to 64.4% of total serum AAT (11.9 μM). Increases in functional AAT activity were consistent with M-AAT production and were accompanied by 60.3% decrease in Z-AAT protein. In the 200 and 400 mg single dose cohorts, M-AAT levels increased to 4.8 μM and 5.3 μM, respectively. During the 200 mg single dose phase, one participant experienced an acute-phase response due to a kidney stone, during which total serum AAT levels reached 20.6 μM. WVE-006 has been generally safe and well tolerated; all adverse events have been mild to moderate, with no serious adverse events. Conclusions These data, which show production of M-AAT, lowering of Z-AAT protein, and endogenous upregulation of AAT protein in individuals with a ZZ genotype during stress provide proof-of-concept for the first RNA editing therapy to enter clinical testing. This abstract is funded by: Wave Life Sciences

Open article ↗



2026-05-20 | Optimization of Alpha-1 Antitrypsin Expression from Adeno-Associated Virus Vectors.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder caused by mutations in SERPINA1 that result in insufficient circulating alpha-1 antitrypsin (AAT) and progressive lung and liver diseases. Adeno-associated virus (AAV)-mediated gene therapy offers the potential for durable AAT expression; however, achieving therapeutic serum concentrations (≥11 µM) at clinically acceptable vector doses remains a major challenge. Here, we evaluated multiple AAV vector design strategies to enhance AAT expression and increase vector potency, thereby reducing the required dose to levels below those associated with severe adverse events. Using AAV1- and AAV8-based platforms, we compared promoter and enhancer configurations, codon optimization of the SERPINA1 transgene, single-stranded versus self-complementary vector genomes, alternative polyadenylation signals, and an engineered oxidation-resistant AAT variant. Across mouse and ferret models, the chicken β-actin expression cassette consistently produced higher AAT levels than a liver-specific promoter variant despite comparable vector biodistribution, reflecting superior intrinsic transcriptional activity or an important contribution. Codon optimization did not enhance expression and, in some cases, modestly reduced AAT levels. Self-complementary AAV vectors exhibited reduced overall expression due to required promoter truncation, yielding lower transgene output than full-length single-stranded constructs. Modifications to polyadenylation signals or enhancer combinations did not improve expression. An oxidation-resistant AAT variant resulted in lower circulating levels but may retain therapeutic potential through enhanced functional stability. Collectively, these findings demonstrate that promoter strength and cassette architecture are dominant determinants of AAV-AAT potency and that full-length, single-stranded vectors with robust regulatory elements provide the highest expression. This work defines key parameters governing AAT expression in vivo and provides a foundation for next-generation AAV designs aimed at achieving therapeutic efficacy at safer, lower vector doses for the treatment of AATD.

Open article ↗



2026-05-04 | Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by intracellular retention of mutant Z (Pi*Z) alpha-1 antitrypsin (AAT) within hepatocytes, resulting in progressive liver disease. Currently, no approved pharmacological therapies exist for AATD-associated hepatic injury. Emerging preclinical evidence indicates that inhibition of mammalian target of rapamycin (mTOR) ameliorates liver pathology in AATD; however, the status of mTOR activity and its regulatory mechanisms under Pi*Z AAT-induced cellular stress remains incompletely understood. In this study, we investigated alterations in mTOR signaling and its upstream regulatory pathways using a gene-edited human hepatocyte model harboring the Pi*Z mutation (Huh7.5Z cells) and a Pi*Z AAT transgenic mouse model. Attenuation of mTORC1 activity was observed in both cellular and murine Pi*Z models. In vitro analyses demonstrated activation of AMP-activated protein kinase (AMPKα), a key inhibitory regulator of mTORC1, accompanied by paradoxical activation of Akt and the unfolded protein response (UPR) branch ATF6α. Pharmacological inhibition of mTOR significantly reduced intracellular Pi*Z AAT accumulation, alleviated ER stress, and suppressed apoptotic signaling through enhancement of autophagy. These findings reveal that hepatocytes adapt to Pi*Z AAT-induced stress through coordinated regulation of mTOR by AMPK, Akt, and ATF6α pathways. This study provides mechanistic insight into metabolic and stress-response signaling in AATD and identifies mTOR modulation as a promising therapeutic strategy for AATD-associated liver disease.

Open article ↗



2026-08-08 | p62/SQSTM1-KEAP1 complex prevents clearance of ubiquitinated Z alpha-1 antitrypsin and aggravates liver proteotoxicity.

Liver disease in Alpha-1 antitrypsin deficiency (AATD) is caused by the toxic accumulation of mutant Z alpha-1 antitrypsin (Z-AAT) within the endoplasmic reticulum (ER) of hepatocytes. Livers from PiZ transgenic mice expressing the human Z-AAT and AATD patients were both found to have increased p62/SQSTM1, a multifunctional protein involved in protein homeostasis, consistent with previous reports. However, whether p62/SQSTM1 is a marker of Z-AAT globules or plays an active role in Z-AAT proteostasis is unclear. The goal of this study was to elucidate the involvement of p62/SQSTM1 in the formation of Z-AAT globules that are responsible for liver injury in AATD. In the present study, we found that p62/SQSTM1 decorated ubiquitin-positive, Periodic-Acid Shiff-diastase-resistant Z-AAT globules and interacted with Z-AAT at the ER-cytosol interface. Genetic ablation of p62/SQSTM1 in PiZ mice (PiZ;p62-/-) led to marked reduction in hepatic Z-AAT globules and polymers, and decreased serum Z-AAT, highlighting a central role for p62/SQSTM1 in disease pathogenesis. Moreover, hepatocyte-specific somatic deletion of the ubiquitin-association (UBA) domain of p62/SQSTM1 reduced Z-AAT aggregation. Furthermore, KEAP1 was identified as a binding partner of p62/SQSTM1-Z-AAT complex, leading to nuclear translocation and activation of NRF2. Inhibition of KEAP1-p62/SQSTM1 interaction reduced the abundance of p62 and phosphorylated p62, decreased intracellular Z-AAT, and redistributed NRF2 to the cytoplasm. In conclusion, this study identifies p62/SQSTM1 as a regulator of Z-AAT proteostasis and link Z-AAT/p62 accumulation to KEAP1 sequestration and NRF2 pathway activation in liver disease due to Z-AAT.

Open article ↗



2026-07-29 | From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases.

Rare genetic liver diseases collectively affect millions of individuals worldwide and encompass a heterogeneous group of monogenic disorders including Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, urea cycle disorders, progressive familial intrahepatic cholestasis, and acute hepatic porphyrias. While conventional management relies on dietary modification, pharmacotherapy, and ultimately liver transplantation, the advent of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has opened transformative therapeutic avenues. This review provides a comprehensive and critical appraisal of the current landscape of CRISPR-based therapies for genetic liver diseases, from preclinical proof-of-concept studies to landmark clinical trials. We examine the evolution from conventional Cas9 nuclease-mediated editing to precision tools including base editors and prime editors, which enable single-nucleotide corrections without inducing double-strand DNA breaks. The role of lipid nanoparticle delivery systems in achieving efficient hepatocyte-targeted delivery is discussed, alongside emerging challenges in pediatric dosing and immunogenicity. We highlight the paradigm shift toward personalized, patient-specific CRISPR therapies, exemplified by the first-in-human bespoke gene editing treatment delivered in 2025. Competing nucleic acid technologies, including RNA interference and antisense oligonucleotides, are compared in terms of durability, safety, and cost-effectiveness. Finally, we critically evaluate the evolving regulatory landscape and propose a priority framework for selecting genetic liver diseases most amenable to CRISPR-based correction. This review underscores that CRISPR gene editing is transitioning from experimental promise to clinical reality for genetic liver diseases, with personalized approaches poised to redefine the treatment paradigm.

Open article ↗



2026-06-01 | B101-10 RNA Editing for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)

Abstract Rationale Severe AATD is commonly caused by homozygous mutations in the SERPINA1 gene (Pi*ZZ), resulting in misfolded Z-AAT protein in the liver and offering decreased protection for the lung against neutrophil elastase. Current standard of care focuses on augmenting serum AAT levels through weekly infusions of human plasma-purified AAT to maintain serum levels above a putative protective threshold (11 µM). Liver disease is not addressed by this intervention. WVE-006, an investigational N-Acetylgalactosamine-conjugated RNA editing oligonucleotide, is designed to recruit endogenous ADAR enzymes to edit SERPINA1 mRNA in hepatocytes, replacing Z-AAT with M-AAT synthesis. This approach aims to increase serum M-AAT levels while reducing Z-AAT, preserve endogenous regulation of AAT expression, and address both lung and liver manifestations of severe AATD. Methods RestorAATion-2 (NCT06405633) is an ongoing phase 1b/2a clinical trial evaluating the safety, tolerability, pharmacodynamics, and pharmacokinetics of single- and multiple-ascending doses of WVE-006 (200, 400, 600 mg; n = 8 per cohort) in individuals with a ZZ genotype. Participants received a single subcutaneous dose of WVE-006 with a 12-week observation period, followed by biweekly (200 mg) or monthly doses (400, 600 mg) for 12 weeks, with a subsequent 12-week observation period. Serum levels of M-AAT, Z-AAT and total (M + Z) AAT were measured by LC-MS/MS assays, while functional AAT levels were assessed by a neutrophil elastase inhibition assay. Results In the 200 mg multidose cohort, mean maximum serum M-AAT levels reached 7.2 μM in ZZ individuals, corresponding to 64.4% of total serum AAT (11.9 μM). Increases in functional AAT activity were consistent with M-AAT production and were accompanied by 60.3% decrease in Z-AAT protein. In the 200 and 400 mg single dose cohorts, M-AAT levels increased to 4.8 μM and 5.3 μM, respectively. During the 200 mg single dose phase, one participant experienced an acute-phase response due to a kidney stone, during which total serum AAT levels reached 20.6 μM. WVE-006 has been generally safe and well tolerated; all adverse events have been mild to moderate, with no serious adverse events. Conclusions These data, which show production of M-AAT, lowering of Z-AAT protein, and endogenous upregulation of AAT protein in individuals with a ZZ genotype during stress provide proof-of-concept for the first RNA editing therapy to enter clinical testing. This abstract is funded by: Wave Life Sciences

Open article ↗



2026-05-20 | Optimization of Alpha-1 Antitrypsin Expression from Adeno-Associated Virus Vectors.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder caused by mutations in SERPINA1 that result in insufficient circulating alpha-1 antitrypsin (AAT) and progressive lung and liver diseases. Adeno-associated virus (AAV)-mediated gene therapy offers the potential for durable AAT expression; however, achieving therapeutic serum concentrations (≥11 µM) at clinically acceptable vector doses remains a major challenge. Here, we evaluated multiple AAV vector design strategies to enhance AAT expression and increase vector potency, thereby reducing the required dose to levels below those associated with severe adverse events. Using AAV1- and AAV8-based platforms, we compared promoter and enhancer configurations, codon optimization of the SERPINA1 transgene, single-stranded versus self-complementary vector genomes, alternative polyadenylation signals, and an engineered oxidation-resistant AAT variant. Across mouse and ferret models, the chicken β-actin expression cassette consistently produced higher AAT levels than a liver-specific promoter variant despite comparable vector biodistribution, reflecting superior intrinsic transcriptional activity or an important contribution. Codon optimization did not enhance expression and, in some cases, modestly reduced AAT levels. Self-complementary AAV vectors exhibited reduced overall expression due to required promoter truncation, yielding lower transgene output than full-length single-stranded constructs. Modifications to polyadenylation signals or enhancer combinations did not improve expression. An oxidation-resistant AAT variant resulted in lower circulating levels but may retain therapeutic potential through enhanced functional stability. Collectively, these findings demonstrate that promoter strength and cassette architecture are dominant determinants of AAV-AAT potency and that full-length, single-stranded vectors with robust regulatory elements provide the highest expression. This work defines key parameters governing AAT expression in vivo and provides a foundation for next-generation AAV designs aimed at achieving therapeutic efficacy at safer, lower vector doses for the treatment of AATD.

Open article ↗



2026-05-04 | Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by intracellular retention of mutant Z (Pi*Z) alpha-1 antitrypsin (AAT) within hepatocytes, resulting in progressive liver disease. Currently, no approved pharmacological therapies exist for AATD-associated hepatic injury. Emerging preclinical evidence indicates that inhibition of mammalian target of rapamycin (mTOR) ameliorates liver pathology in AATD; however, the status of mTOR activity and its regulatory mechanisms under Pi*Z AAT-induced cellular stress remains incompletely understood. In this study, we investigated alterations in mTOR signaling and its upstream regulatory pathways using a gene-edited human hepatocyte model harboring the Pi*Z mutation (Huh7.5Z cells) and a Pi*Z AAT transgenic mouse model. Attenuation of mTORC1 activity was observed in both cellular and murine Pi*Z models. In vitro analyses demonstrated activation of AMP-activated protein kinase (AMPKα), a key inhibitory regulator of mTORC1, accompanied by paradoxical activation of Akt and the unfolded protein response (UPR) branch ATF6α. Pharmacological inhibition of mTOR significantly reduced intracellular Pi*Z AAT accumulation, alleviated ER stress, and suppressed apoptotic signaling through enhancement of autophagy. These findings reveal that hepatocytes adapt to Pi*Z AAT-induced stress through coordinated regulation of mTOR by AMPK, Akt, and ATF6α pathways. This study provides mechanistic insight into metabolic and stress-response signaling in AATD and identifies mTOR modulation as a promising therapeutic strategy for AATD-associated liver disease.

Open article ↗



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Drug Discovery Landscape

42 orphan drug designations for Alpha-1-antitrypsin deficiency, including 1 approved therapy.

42 orphan drug designations for Alpha-1-antitrypsin deficiency, including 1 approved therapy.

Drug

Therapy type

Regulator

Orphan designation

Approval

Sponsor

Guide RNA against the human SERPINA1 gene, mRNA encoding a CRISPR-associated endonuclease Cas9 against the human SERPINA1 gene

gene editing enzymes

EMA

2026-07-24

—

Voisin Consulting Life Sciences

Efdoralprin alfa

proteins

EMA

2025-12-09

—

Sanofi B.V.

RNA editing antisense oligonucleotide (ASO)

oligonucleotides

FDA

2025-11-19

—

AIRNA Corporation

in vivo target-primed reverse transcription genome editing product consisting of two chemically modified RNA drug substances: a messenger RNA, and a template guide RNA formulated in a lipid nanoparticle delivery vehicle comprised of 4 lipids to target the pathogenic PiZ allele in the SERPINA1 gene

RNAs

FDA

2025-11-06

—

Tessera Therapeutics, Inc.

RNA editing antisense oligonucleotide against the Z mutation of the human SERPINA1 mRNA transcript, sodium salt

oligonucleotides

EMA

2025-08-22

—

Parexel International (IRL) Limited

a lipid nanoparticle-based therapy consisting of a guide RNA that targets the SERPINA1-c.1096G>A allele and a messenger RNA that encodes an ABE protein

gene editing enzymes

FDA

2025-05-28

—

Beam Therapeutics

lipid nanoparticles containing base editor CRISPR-Cas9 messenger RNA (mRNA) and a single guide RNA (sgRNA) targeting SERPINA1 gene

gene editing enzymes

FDA

2025-04-09

—

Yoltech Therapeutics Co., Ltd

RNA editing antisense oligonucleotide (ASO) KB100967 directed at the Z mutation of the human SERPINA1 mRNA transcript, encapsulated in a lipid nanoparticle

oligonucleotides

FDA

2025-03-12

—

Korro Bio, Inc.

Alvelestat

small molecules

EMA

2025-01-16

—

Mereo BioPharma Europe B.V.

N-[(1R)-1-[(S)-(2-Chloro-3-fluorophenyl)hydroxymethyl]butyl]-7-fluoro-2,3-dihydro-2-oxo-1H-indole-4-carboxamide

small molecules

EMA

2024-07-25

—

BioMarin International Limited

oxoindoline carboxamide compound

small molecules

FDA

2023-12-12

—

BioMarin Pharmaceutical Inc.

A replication-defective, non-integrating herpes simplex virus type 1-based vector engineered to express full-length, functional human alpha-1 antitrypsin

gene therapies

FDA

2023-09-01

—

Krystal Biotech, Inc.

IgG4 Fc linked recombinant human AAT (alpha-1 antitrypsin)

proteins

FDA

2022-03-02

—

Sanofi Aventis US. LLC (A Sanofi Company)

Alvelestat

small molecules

FDA

2021-10-25

—

Mereo Biopharma 4 Limited

CHO cell line produced human Alpha-1 Antitrypsin (CHO-AAT) protein

proteins

FDA

2020-10-19

—

Caravella Biopharma SA

a synthetic double-stranded RNA oligonucleotide conjugated to N-acetyl-D-galactosamine aminosugar residues

oligonucleotides

FDA

2020-03-16

—

Dicerna Pharmaceuticals, Inc.

Recombinant human alpha-1 antitrypsin from Oryza sativa

proteins

FDA

2020-02-19

—

Wuhan Healthgen Biotechnology Corporation

Belcesiran

RNAs

EMA

2019-12-16

—

Novo Nordisk A/S

N-acetylgalactosamine-conjugated synthetic double-stranded oligomer specific to serpin family A member 1 gene

oligonucleotides

EMA

2018-07-31

—

Takeda Pharma A/S

double stranded oligomer ADS-001 RNA interference-based liver targeted therapeutic

oligonucleotides

FDA

2018-02-14

—

Takeda Development Center Americas, Inc.

three-dimensional bioprinted therapeutic liver tissue

cell therapies

FDA

2017-12-21

—

Organovo Inc.

hyaluronic acid

small molecules

FDA

2017-01-18

—

Gerard M. Turino, MD

Double-stranded oligomer specific to the SERPINA1 gene and containing a cholesterol-conjugated acyclic nucleobase analogue [API-AAT (AD00370)]

oligonucleotides

EMA

2016-01-11

—

Pharma Gateway AB

double stranded oligomer AD00370 RNA interference-based liver targeted therapeutic

RNAs

FDA

2015-06-09

—

Arrowhead Research Corporation

Cyclo[L-alanyl-L-seryl-L-isoleucyl-L-prolyl-L-prolyl-L-glutaminyl-L-lysyl-L-tyrosyl-D-prolyl-L-prolyl-(2S)-2-aminodecanoyl-L-alpha-glutamyl-L-threonyl] acetate salt

peptides

EMA

2013-03-20

—

Santhera Pharmaceuticals (Deutschland) GmbH

alpha1 proteinase inhibitor (human)

proteins

FDA

2010-01-29

—

Grifols Therapeutics, Inc.

Alpha-1 proteinase inhibitor (inhalation use)

proteins

EMA

2008-06-03

—

Grifols Deutschland GmbH

Recombinant adeno-associated viral vector containing human alpha-1 antitrypsin gene

gene therapies

EMA

2007-03-20

—

Propharma Group The Netherlands B.V.

Human alfa-1-proteinase inhibitor

proteins

EMA

2006-02-16

—

Octapharma (IP) Limited

Alpha1-Proteinase Inhibitor (Human)

proteins

FDA

2004-12-22

—

Kamada Ltd.

Alpha-1 antitrypsin (inhalation use)

proteins

EMA

2004-11-16

—

Kamada Ireland Limited

recombinant adeno-associated virus alpha 1-antitrypsin vector

gene therapies

FDA

2003-01-27

—

University of Massachusetts Medical School

Human alpha1-proteinase inhibitor, recombinant

proteins

EMA

2002-04-30

—

Aptiv Solutions (UK) Limited

hyaluronic acid

small molecules

FDA

2002-03-19

—

CoTherix

recombinant human alpha-1 antitrypsin (rAAT)

proteins

FDA

2001-08-28

—

AiroMedica LLC

Human Alpha1-Proteinase Inhibitor (respiratory use)

proteins

EMA

2001-07-09

—

CSL Behring GmbH

Human alpha1-proteinase inhibitor, recombinant

proteins

EMA

2001-05-30

—

Grifols Deutschland GmbH

Alpha1-proteinase inhibitor (human)

proteins

FDA

1999-11-24

—

CSL Behring L.L.C.

Transgenic human alpha 1 antitrypsin

gene therapies

FDA

1999-05-19

—

PPL Therapeutics (Scotland) Limited

Recombinant secretory leucocyte protease inhibitor

proteins

FDA

1991-03-29

—

Amgen Inc.

Alpha1-proteinase inhibitor (human) [Prolastin]

proteins

FDA

1984-12-07

1987-12-02

Bayer Corporation

Alpha-1-antitrypsin (recombinant DNA Origin)

proteins

FDA

1984-01-01

—

Chiron Corporation

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At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
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Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

About

Home

Team

Contact

Our AI

Solutions

How it works

Diseases

More

Blog

Terms of Use

Privacy Policy

Copyright © 2026 Explority AI Inc.

Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

About

Home

Team

Contact

Our AI

Solutions

How it works

Diseases

More

Blog

Terms of Use

Privacy Policy

Copyright © 2026 Explority AI Inc.