Lacripep (synthetic lacritin) / TearSolutions - LARVOL DELTA

Ophthalmic Treatments and Evolving Management of Sjögren's Disease: An Overview. (PubMed, J Clin Med) - "Additionally, emerging therapeutics are shifting care from palliative lubrication to targeted secretomotor and biological reactivation, including cold thermosensory TRPM8 agonists (acoltremon 0.003%), water-free formulations (0.1% cyclosporine, perfluorohexyloctane), reactive aldehyde species (RASP) modulators (reproxalap), syndecan-1 receptor agonists (Lacripep), systemic B-cell depleting biotherapy (ianalumab), trigeminal neurostimulation, and combined intense pulsed light with meibomian gland expression (IPL + MGX). Ophthalmic SjD management has evolved from palliative lubrication toward a stepwise, mechanism-directed paradigm integrating novel diagnostics, secretomotor stimulation, mechanical protection, and biologic disease modification; dedicated SjD-specific trials remain essential to validate these emerging interventions."

Journal • Review • Conjunctivitis • Dry Eye Disease • Inflammation • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • MMP9 • SDC1 • TRPM8

TearSolutions Receives FDA Orphan Drug and Fast Track Designations for Lacripep in Neurotrophic Keratitis and Initiates Phase 2 Clinical Trial with First Patients Dosed (Businesswire)

Fast track • Orphan drug • Trial status • Ophthalmology

Lacripep Treatment Reduces Ocular GVHD Severity & Local Inflammatory Cytokine Response (ARVO 2026) - "The improvement in keratopathy and reduced CD4+IFNγ+ and CD8+IFNγ+ cells highlight potential immune modulation at the ocular surface. These findings support Lacripep as a topical treatment for oGVHD and warrant an adequately powered study to achieve statistical significance."

Ocular Inflammation • Ophthalmology • CD8 • IFNG • IL17A • IL2 • IL4 • PTPRC • TNFA

Lacripep, a Synthetic Peptide of the Tear Protein Lacritin, Promotes Corneal Nerve Regeneration and Improves Corneal Hyperalgesia in a Murine Model of Neuropathic Corneal Pain (ARVO 2026) - "Corneal stromal nerve density was higher in Lacripep (13.0±2.2, 16.0±0.8, 14.6±1.2 mm/mm2 for 1 μM, 4 μM, and 22 μM) and mNGF (11.2±0.7) groups (all p<0.05) at 13 dps than Veh (9.6±1.5) and PBS (10.1±1.8) groups. Conclusions Lacripep alleviates corneal hyperalgesia, promotes sensation recovery and nerve regeneration without compromising epithelial integrity in NCP mice, highlighting its therapeutic activity in a model of NCP."

Preclinical • Ocular Inflammation • Ophthalmology • LACRT

A Multicenter, Randomized, Vehicle-Controlled, Double-Masked to Open-Label Study to Evaluate the Safety and Efficacy of Lacripep 4 μM Ophthalmic Solution in Subjects With Neurotrophic Keratitis (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: TearSolutions, Inc.

New P2 trial • Keratitis • Ocular Inflammation • Ophthalmology

Lacripep for Corneal Wound Healing Study (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Not yet recruiting ➔ Recruiting

Enrollment open

Lacripep for Corneal Wound Healing Study (clinicaltrials.gov) - P2 | N=88 | Not yet recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

New P2 trial

Transcriptomic Exploration of Human Corneal Epithelial Cells Treated with Lacritin Ocular Surface Homeostasis Restorative Peptide 'N-94' in the Absence or Presence of Lacritin Signaling Receptor GPR87 and without or with Dry Eye Inflammatory Stress (ARVO 2024) - "Since replacement therapy with overlapping peptide 'N-94/C-6' (Lacripep) in severe Sjogren's Sydrome dry eye is efficacious, it is important to gain a broader transcriptomic understanding of gene expression changes involved... Lacritin N-94 profoundly benefits the transcriptomic landscape of human corneal epithelial cells, both in the absence and presence of inflammatory stress, thus helping to explain its benefit in dry eye disease. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.: Towards understanding the biological basis of dry eye disease, we performed an unbiased biochemical screen thereby identifying the tear protein 'lacritin' that is selectively deficient in dry eye."

Dry Eye Disease • Ocular Inflammation • Ophthalmology • IFNG • LACRT • SDC1

Lacritin bactericidal tear proteoform 'N-104' binds tear thrombin and synergizes with its GKY20 peptide to efficiently kill pathogenic P. aeruginosa strain PA14 (ARVO 2023) - "Purpose Processing of lacritin in basal tears by cysteine, serine and metalloproteinase activity yields C-terminal proteoforms including tear stabilizing, basal tear agonist and neurotrophic N-94 and N-94/C-6 (the latter ['Lacripep'] the subject of a recent phase I/II clinical trial)...Multidrug resistance of Pseudomonas is a major worldwide problem, as highlighted by the World Health Organization. A logical outcome is the development of new therapeutics."

Ocular Infections • Ophthalmology • ELANE • F2 • GSN • IGKC • LACRT • Mammaglobin • SCGB2A1

Promoting Corneal Nerve Regeneration with Synthetic Proteins (ARVO 2023) - "Most recently, we revealed novel corneal epithelial subtypes and striking alterations in epithelial cell differentiation in Aire KO mice that appear to be mediated by alterations in basal cell signaling and disruption of epithelial-neuronal crosstalk. This work has advanced our fundamental understanding of the mechanisms underlying ocular surface disruption in dry eye and by further elucidating lacripep’s potential as a pro-regenerative therapy, we will inform the identification of novel diagnostic features and innovative therapeutic approaches to effectively"

Conjunctivitis • Dry Eye Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • LACRT

A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration. (PubMed, Cell Rep) - "Intriguingly, the restorative effects of Lacripep occur despite extensive immune cell infiltration, suggesting tissue reinnervation and regeneration can be achieved under chronic inflammatory conditions. In summary, our data highlight Lacripep as a first-in-class regenerative therapy for returning the cornea to a near homeostatic state in individuals who suffer from dry eye."

Journal • Dry Eye Disease • Immunology • Inflammation • Ocular Inflammation • Ophthalmology

Lacripep for the Treatment of Primary Sjögren's-Associated Ocular Surface Disease: Results of the First-In-Human Study. (PubMed, Cornea) - "This first-in-human study of Lacripep in patients with primary Sjögren's syndrome demonstrated clinically significant improvements in specific signs and symptoms on which to base future studies. This study established safety and tolerability and potential metrics of efficacy in patients with moderate to severe disease. Further work on appropriate dosing and concentration is ongoing."

Journal • P1 data • Anesthesia • Immunology • Sjogren's Syndrome • LACRT

Dissection of the SDC1-GPR87 Coreceptor-Receptor Complex that Captures Tear Lacritin for Promotion and Restoration of Ocular Surface Homeostasis (ARVO 2022) - "Lacritin targets the outer loop domains of GPR87 (particularly loop 3) as part of a preformed SDC1-GPR87 complex - the latter linked by glycosaminoglycans and by cytoplasmic SDC1 (PDZ binding) and GPR87 ('DRY') domains to regulate ocular surface health. Layman Abstract: Finding an effective treatment for dry eye is challenging and has largely focused on reducing inflammation, with modest outcomes. Building on years of bench, preclinical and now first-in-human studies, we propose topical lacritin peptide 'N-94 or N-94/C-6 (Lacripep)' as a novel regenerative, natural replacement therapy approach for dry eye."

Dry Eye Disease • Ocular Inflammation • Ophthalmology • LACRT • SDC1

Dry eye: What’s in the pipeline? (Review of Optometry) - "Francis Mah, MD...is intrigued by the drug’s mechanism of action. 'I think it’s really unique in that you’re potentially stimulating all three sources or layers of the tear film,' he says....There are several new cyclosporine products in various stages of development. According to John Sheppard, MD, who is in practice in Norfolk, Virginia, Novaliq is investigating two products based on the company's semifluorinated alkane water-free vehicle. 'They've come up with the first truly new vehicle [EyeSol] for topical eye medications in over a generation,' Dr. Sheppard says....Dr. Sheppard says that the beauty of looking at both osmolarity and MMP-9 is that the osmolarity acts as a normalizing comparator to further refine the accuracy of the MMP-9 test."

Media quote

[VIRTUAL] LacripepTM-like Peptide N-104 Promotes Beta Cell Proliferation in Murine Pancreatic Islets (ATC 2021) - "Our data indicate that systemic N-104 treatment promoted single cell proliferation in islets, especially that of beta cells, without affecting exocrine acinar cell proliferation."

Preclinical • CD44 • LACRT

[VIRTUAL] LacripepTM-like Peptide N-104 Increases Insulin Secretion and Promotes Islet Transplantation Outcomes (ATC 2021) - "Islet viability, glucose stimulated insulin secretion, and transplantation outcomes indicate that N-104 is the most viable candidate for clinical translation as an interventional agent to promote islet transplantation outcomes."

Transplantation • LACRT

[VIRTUAL] Topical lacritin C-terminal peptide 'LacripepTM' significantly reduces both inferior corneal staining and burning/stinging in primary Sjögren's Syndrome dry eye (ARVO 2021) - P1/2 | "Lacripep™ appears to be rapidly efficacious for both sign and symptom in primary Sjögren's syndrome, the most severe form of dry eye. This is the largest ophthalmic trial to date in primary Sjögren's Syndrome dry eye and was the first-in-human clinical study conducted with Lacripep™ as the active ingredient."

Dry Eye Disease • Ophthalmology • LACRT

Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium. (PubMed, Int J Mol Sci) - "However, cells at low density treated with 1 μM LP-A96 generated a 210-fold higher number of exosomes compared to those treated at low density with Lacripep. As monovalent Lacripep is capable of enhancing cell motility but not exosome biogenesis, activation of exosome biogenesis by LP-A96 not only suggests its utility as a novel molecular tool to study the Lacritin biology in the corneal epithelium but also implies activity as a potential therapeutic peptide that can further improve ocular surface health through the induction of exosomes."

Journal • LACRT • SDC1

[VIRTUAL] LacripepTM and its Analogs Act as Novel Interventional Agents to Promote Long-Term Islet Transplantation Outcomes (ATC 2020) - P1/2 | "Lacripep™ and its analogs represent a novel class of interventional agents that can significantly enhance islet viability, increase insulin secretion, and promote long term longitudinal graft survival, indicating their immense potential for promoting clinical islet transplantation outcomes."

Diabetes • Dry Eye Disease • Immunology • Ophthalmology • Transplantation • LACRT