AI Drug Discovery for Pharma and Biotech

Drug discovery

9

drugs

With orphan designations

Overview

Limbal stem cell deficiency (LSCD) is a vision-threatening condition caused by dysfunction or loss of limbal stem cells, impairing corneal epithelial regeneration. This leads to conjunctivalization, neovascularization, and opacity, with symptoms including chronic pain, photophobia, and irreversible vision loss. Etiologies range from trauma (chemical burns, surgery) to autoimmune disorders (Stevens-Johnson syndrome) and congenital conditions (aniridia). Diagnosis relies on clinical evaluation and staging systems, while treatment combines medical optimization of the ocular surface and surgical stem cell transplantation [1][4][9][12].

Population

  • Primarily affects young, working-age males (mean age ~35 years), with higher incidence in rural populations and those with limited education [12][16][19].

  • Unilateral cases (50–60%) are more common than bilateral, often linked to chemical injuries or contact lens misuse; bilateral cases typically stem from autoimmune/inflammatory conditions [2][4][12].

Burden

  • Accounts for 15–20% of corneal blindness globally, with vision <2/60 in ~50% of patients [4][12][19].

  • Causes significant economic and social impacts, particularly in low-resource settings, due to chronic pain, disability, and complex treatment needs [4][12][16].

Therapies

  • Medical: Lubricants, anti-inflammatory agents (steroids, cyclosporine), and autologous serum drops for early-stage disease [6][11][16].

  • Surgical:

    • Autografts (e.g., SLET, CLAU) for unilateral LSCD (success rates >70%) [6][8][11].

    • Allografts (KLAL, CLAL) or keratoprostheses for bilateral disease, requiring lifelong immunosuppression [5][8][16].

Categories: rare ophthalmic disorders

Research Papers

1,449 drug discovery papers related to Limbal stem cell deficiency, with 3 first-in-class and 9 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

1,449 drug discovery papers related to Limbal stem cell deficiency, with 3 first-in-class and 9 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

2026-06-30 | 3% diquafosol sodium combined with 0.1% fluorometholone for postoperative dry eye in pterygium patients with preoperative tear deficiency: a pilot retrospective study

Background To evaluate the clinical efficacy and safety of 3% diquafosol sodium combined with 0.1% fluorometholone for postoperative dry eye in pterygium patients with preoperative tear deficiency. Methods This single-center retrospective study included 82 pterygium patients (82 eyes) with preoperative tear deficiency who underwent pterygium excision combined with limbal stem cell transplantation. Patients were divided into an observation group (diquafosol + fluorometholone, n = 42) and a control group (sodium hyaluronate + fluorometholone, n = 40). Tear break-up time (BUT), corneal fluorescein staining (CFS) score, Ocular Surface Disease Index (OSDI), Schirmer I test (SIt), and intraocular pressure (IOP) were assessed preoperatively and at 2 and 4 weeks postoperatively. Adverse events and complications were recorded. Results Eighty patients completed follow-up (41 in observation group, 39 in control group). At 4 weeks postoperatively, the observation group showed significantly longer BUT, lower CFS and OSDI scores, and higher SIt values compared to the control group (all p &lt; 0.05). No significant intergroup differences in IOP were observed at any time point. Transient ocular stinging occurred in 2 patients (4.88%) in the observation group, with no severe complications in either group. Conclusion In this pilot study, the combination of 3% diquafosol sodium and 0.1% fluorometholone showed preliminary evidence of improving tear film stability, repairing ocular surface damage, and alleviating dry eye symptoms in pterygium patients with preoperative tear deficiency, without significantly affecting IOP. Its efficacy appeared superior to sodium hyaluronate combined with fluorometholone. These findings support further investigation in larger, longer-term randomized controlled trials.

Open article ↗



2026-06-26 | Induced Pluripotent Stem Cells in Corneal Regeneration: Biological Progress, Translational Barriers and Clinical Outlook.

Corneal blindness remains a major cause of visual impairment worldwide and may result from trauma, infectious keratitis, degenerative disorders, endothelial dysfunction, and limbal stem cell deficiency (LSCD). Although corneal transplantation remains the standard treatment for advanced disease, its effectiveness is limited by donor tissue shortage, immune-mediated rejection, postoperative complications, and progressive graft failure. These limitations have accelerated interest in regenerative approaches aimed at restoring native corneal structure and function. Induced pluripotent stem cells (iPSCs) have emerged as a promising platform for corneal regeneration because of their pluripotency, self-renewal capacity, and potential for autologous or immune-compatible therapy. Recent advances in differentiation protocols have enabled the generation of corneal epithelial-like cells, stromal keratocyte-like cells, and corneal endothelial-like cells from iPSCs. Preclinical studies have demonstrated encouraging improvements in corneal transparency, epithelial restoration, fibrosis reduction, and endothelial function, while early clinical investigations, particularly in LSCD, have reported favorable short-term safety and functional outcomes. However, major translational barriers remain, including tumorigenicity, immunogenicity, genomic instability, manufacturing complexity, scalability, and long-term safety concerns. Stromal regeneration also remains comparatively underdeveloped relative to epithelial and endothelial applications. This review summarizes current differentiation strategies, biological mechanisms, preclinical and early clinical evidence, and the principal translational challenges associated with iPSC-based corneal regeneration. Overall, iPSC-derived corneal therapies demonstrate considerable regenerative potential, although further standardization, long-term safety evaluation, and multicenter clinical validation remain necessary before widespread clinical adoption.

Open article ↗



2026-06-13 | Current Practices, Evolving Techniques, and Immunologic Challenges in Living and Deceased Donor Limbal Stem Cell Transplantation.

This review focuses on allogeneic sources for restoring the ocular surface using limbal stem cell transplantation. We outline the current practices, evolving techniques, and immunologic challenges in living-related and deceased donor limbal stem cell transplantation. The diagnosis and staging guidelines for limbal stem cell deficiency are reviewed. We also explore the currently available treatment approaches, including the Cincinnati protocol for donor/recipient selection criteria and systemic immunosuppression (SI) regimen. Utilization of panel reactive antibody, HLA typing, ABO typing, and donor specific antibodies are highlighted. The traditional techniques as well as more novel variations are described. The importance of 3-agent SI protocols and patient adherence are emphasized to ensure excellent long-term outcomes. The primary immunologic challenge of allogeneic limbal stem cell transplantation, rejection, is also discussed in detail with recommended treatments, including a newer role for intravenous immunoglobulin. Other evolving practices have included a greater reliance on living-related conjunctival limbal allograft over deceased donor keratolimbal allograft due to improved outcomes, decreasing SI in older populations, and lengthening SI regimens due to the possibility of late acute rejection. Finally, we discuss the future of restoring the ocular surface via cell-based therapies, which may have the potential to decrease rejection.

Open article ↗



2026-06-30 | 3% diquafosol sodium combined with 0.1% fluorometholone for postoperative dry eye in pterygium patients with preoperative tear deficiency: a pilot retrospective study

Background To evaluate the clinical efficacy and safety of 3% diquafosol sodium combined with 0.1% fluorometholone for postoperative dry eye in pterygium patients with preoperative tear deficiency. Methods This single-center retrospective study included 82 pterygium patients (82 eyes) with preoperative tear deficiency who underwent pterygium excision combined with limbal stem cell transplantation. Patients were divided into an observation group (diquafosol + fluorometholone, n = 42) and a control group (sodium hyaluronate + fluorometholone, n = 40). Tear break-up time (BUT), corneal fluorescein staining (CFS) score, Ocular Surface Disease Index (OSDI), Schirmer I test (SIt), and intraocular pressure (IOP) were assessed preoperatively and at 2 and 4 weeks postoperatively. Adverse events and complications were recorded. Results Eighty patients completed follow-up (41 in observation group, 39 in control group). At 4 weeks postoperatively, the observation group showed significantly longer BUT, lower CFS and OSDI scores, and higher SIt values compared to the control group (all p &lt; 0.05). No significant intergroup differences in IOP were observed at any time point. Transient ocular stinging occurred in 2 patients (4.88%) in the observation group, with no severe complications in either group. Conclusion In this pilot study, the combination of 3% diquafosol sodium and 0.1% fluorometholone showed preliminary evidence of improving tear film stability, repairing ocular surface damage, and alleviating dry eye symptoms in pterygium patients with preoperative tear deficiency, without significantly affecting IOP. Its efficacy appeared superior to sodium hyaluronate combined with fluorometholone. These findings support further investigation in larger, longer-term randomized controlled trials.

Open article ↗



2026-06-26 | Induced Pluripotent Stem Cells in Corneal Regeneration: Biological Progress, Translational Barriers and Clinical Outlook.

Corneal blindness remains a major cause of visual impairment worldwide and may result from trauma, infectious keratitis, degenerative disorders, endothelial dysfunction, and limbal stem cell deficiency (LSCD). Although corneal transplantation remains the standard treatment for advanced disease, its effectiveness is limited by donor tissue shortage, immune-mediated rejection, postoperative complications, and progressive graft failure. These limitations have accelerated interest in regenerative approaches aimed at restoring native corneal structure and function. Induced pluripotent stem cells (iPSCs) have emerged as a promising platform for corneal regeneration because of their pluripotency, self-renewal capacity, and potential for autologous or immune-compatible therapy. Recent advances in differentiation protocols have enabled the generation of corneal epithelial-like cells, stromal keratocyte-like cells, and corneal endothelial-like cells from iPSCs. Preclinical studies have demonstrated encouraging improvements in corneal transparency, epithelial restoration, fibrosis reduction, and endothelial function, while early clinical investigations, particularly in LSCD, have reported favorable short-term safety and functional outcomes. However, major translational barriers remain, including tumorigenicity, immunogenicity, genomic instability, manufacturing complexity, scalability, and long-term safety concerns. Stromal regeneration also remains comparatively underdeveloped relative to epithelial and endothelial applications. This review summarizes current differentiation strategies, biological mechanisms, preclinical and early clinical evidence, and the principal translational challenges associated with iPSC-based corneal regeneration. Overall, iPSC-derived corneal therapies demonstrate considerable regenerative potential, although further standardization, long-term safety evaluation, and multicenter clinical validation remain necessary before widespread clinical adoption.

Open article ↗



2026-06-13 | Current Practices, Evolving Techniques, and Immunologic Challenges in Living and Deceased Donor Limbal Stem Cell Transplantation.

This review focuses on allogeneic sources for restoring the ocular surface using limbal stem cell transplantation. We outline the current practices, evolving techniques, and immunologic challenges in living-related and deceased donor limbal stem cell transplantation. The diagnosis and staging guidelines for limbal stem cell deficiency are reviewed. We also explore the currently available treatment approaches, including the Cincinnati protocol for donor/recipient selection criteria and systemic immunosuppression (SI) regimen. Utilization of panel reactive antibody, HLA typing, ABO typing, and donor specific antibodies are highlighted. The traditional techniques as well as more novel variations are described. The importance of 3-agent SI protocols and patient adherence are emphasized to ensure excellent long-term outcomes. The primary immunologic challenge of allogeneic limbal stem cell transplantation, rejection, is also discussed in detail with recommended treatments, including a newer role for intravenous immunoglobulin. Other evolving practices have included a greater reliance on living-related conjunctival limbal allograft over deceased donor keratolimbal allograft due to improved outcomes, decreasing SI in older populations, and lengthening SI regimens due to the possibility of late acute rejection. Finally, we discuss the future of restoring the ocular surface via cell-based therapies, which may have the potential to decrease rejection.

Open article ↗



Access all drug discovery articles and probability of success in trials forecasts:

Access all drug discovery articles and probability of success in trials forecasts:

Drug Discovery Landscape

9 orphan drug designations for Limbal stem cell deficiency, including 1 approved therapy.

9 orphan drug designations for Limbal stem cell deficiency, including 1 approved therapy.

Drug

Therapy type

Regulator

Orphan designation

Approval

Sponsor

Spironolactone

small molecules

EMA

2026-02-23

Dan Mejlachowicz

allogeneic ABCB5-positive limbal stem cells

cell therapies

FDA

2019-03-28

RHEACELL GmbH & Co. KG

Allogeneic ABCB5-positive limbal stem cells

cell therapies

EMA

2018-12-14

Rheacell GmbH & Co. KG

ex vivo expanded autologous human corneal epithelial cells containing stem cells

cell therapies

FDA

2018-04-26

Holostem S.r.l.

Cultured allogeneic corneal limbal stem cells

cell therapies

EMA

2014-10-15

NHS National Services Scotland Trading as Scottish National Blood Transfusion Service

Ex-vivo expanded autologous human corneal epithelium containing stem cells

cell therapies

EMA

2013-07-17

University of Newcastle upon Tyne

Ex-vivo expanded autologous human corneal epithelium containing stem cells [Holoclar]

cell therapies

EMA

2008-11-07

2015-02-19

Holostem S.r.l.

Bio-engineered oral mucosal tissue

cell therapies

FDA

2006-04-27

TissueTech, Inc.

Autologous or allogeneic limbal epithelial stem cells expanded ex vivo on human amniotic membrane

cell therapies

FDA

2005-07-14

TissueTech, Inc.

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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

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

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

Copyright © 2026 Explority AI Inc.