NEXAGON (LUFEPIRSEN OPHTHALMIC GEL)
First-in-class, patent protected product to redefine the PCED treatment paradigm
NOVEL
MECHANISM OF ACTION
Proprietary, unmodified antisense oligonucleotide that inhibits the hemichannel forming protein, connexin43 (Cx43).
DIFFERENTIATED PRODUCT PROFILE
First-in-class product profile optimized for the treatment PCED, recognized as a potential paradigm shift to current standard of care.
ONGOING
CLINICAL EVALUATION
Amber is currently evaluating the
safety and efficacy of NEXAGON (lufepirsen ophthalmic gel) in the clinic for the treatment of PCED.
NEXAGON blocks connexin43 hemichannel formation, leading to restored corneal healing
Nexagon inhibits hemichannel formation, arresting an exaggerated inflammatory cascade (1,2)
Attenuates cytokine-induced cell death, restoring homeostasis and preserving corneal epithelium (1,2)
Restores limbal stem cell function to promote healing (3)
NOVEL MECHANISM OF ACTION
NEXAGON BLOCKS CX43 HEMICHANNEL FORMATION, RESTORES CORNEAL HEALING
PCED
NEXAGON
Connexin43 Regulation
NLRP3 Inflammasome Activation
Pro-inflammatory Cytokines
Impaired Corneal Healing
Decreased Limbal Stem Cell Fxn
Restores Corneal Healing
Restores Limbal Stem Cell Fxn
ATP
ATP
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NEXAGON inhibits hemichannel formation, decreasing extracellular ATP messaging, resulting in NLRP3 signal modulation (1,2)
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Decreased NLRP3 inflammasome activation reduces pro-apoptotic cytokines, cell death, thus promoting healing (1,2)
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Attenuated NLRP3 inflammasome signaling also restores limbal stem cell function, resulting in healing (3)
DIFFERENTIATED PRODUCT PROFILE
Nexagon recognized as potential paradigm shift for the treatment of PCED
ACTIVE MOIETY
Connexin43 antisense oligonucleotide
DOSING FREQUENCY & DURATION
Dosing regimen optimized for the treatment of PCED
FORMULATION
Thermoreversible Gel
OCULAR SIDE EFFECTS
Favorable safety profile
demonstrated in multiple human studies
ADMINISTRATION
In-office topical administration
POTENTIAL INDICATIONS
Rare corneal diseases (PCED, Fuch's), uveitis, keratoconjunctivitis sicca
Nexagon has the potential to be the first approved therapy for the treatment of PCED
NEX-PED-005
(EXPEDE)
Interim Data expected in Q1 '23
A Phase 2, Randomized, Prospective, Double-masked, Vehicle-controlled Study to Assess the Safety and Efficacy of Nexagon® (NEXAGON) Applied Topically in Subjects With Corneal Persistent Epithelial Defects Resulting From Severe Ocular Chemical and/or Thermal Injuries
ONGOING CLINICAL TRIALS
REFERENCES
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Mugisho OO, Green CR, Kho DT, Zhang J, Graham ES, Acosta ML, Rupenthal ID. The inflammasome pathway is amplified and perpetuated in an autocrine manner through connexin43 hemichannel mediated ATP release. Biochim Biophys Acta Gen Subj. 2018;1862(3):385-393.
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Campenhout RV, Gomes AR, De Groof TWM, Muyldermans S, Devoogdt N, Vinken M. Mechanisms Underlying Connexin Hemichannel Activation in Disease. Int J Mol Sci. 2021 Mar 28;22(7):3503.
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Ormonde S, Chou CY, Goold L, Petsoglou C, Al-Taie R, Sherwin T, McGhee CN, Green CR. Regulation of connexin43 gap junction protein triggers vascular recovery and healing in human ocular persistent epithelial defect wounds. J Membr Biol. 2012;245(7):381-388.