A Double-Masked, Randomized, Multi-Center Phase 2 Study to Evaluate the Efficacy and Safety of Lacripep™ in Subjects With Dry Eye Associated With Primary Sjögren's Syndrome

The objective of this study is to evaluate the efficacy and safety of two strengths of Lacripep™ ophthalmic solution versus placebo administered three times daily for four weeks in subjects with a diagnosis of Dry Eye associated with documented Primary Sjögren's Syndrome

开始日期2017-06-30

申办/合作机构

TearSolutions, Inc.

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项与 Lacripep 相关的文献（医药）

2023-07-01·Cornea

Lacripep for the Treatment of Primary Sjögren–Associated Ocular Surface Disease: Results of the First-In-Human Study

Article

作者: Odrich, Marc G ; Laurie, Gordon W ; Tauber, Joseph ; Parsons, Edward C

Purpose::

The purpose of this study was to assess the safety, tolerability, dosing, and efficacy of the active 19 amino acid fragment of lacritin (Lacripep), a broad regulator of ocular surface homeostasis, in the treatment of ocular surface disease associated with primary Sjögren syndrome.

Methods::

Two hundred four subjects were randomized to receive vehicle, 22 μM Lacripep, or 44 μM Lacripep 3 times daily for 28 days, preceded by a 14-day run-in and followed by 14-day washout. Outcome measures were corneal fluorescein staining (CFS), lissamine conjunctival staining, Schirmer with anesthesia, tear break-up time, SANDE scoring, and visual analog scale assessment of symptoms.

Results::

This study established the safety and tolerability of topical treatment with Lacripep in patients with primary Sjögren syndrome. There were few adverse events: Only mild irritation was found in less than 3 percent of patients dosed with Lacripep. Total CFS and Eye Dryness Score were not significantly changed at day 28. Post hoc analysis of patients with Eye Dryness Severity scores of 60 or greater at baseline revealed significant improvements in inferior CFS at 14 and 28 days and complaints of burning and stinging at 14 days. Significant improvement in regional lissamine conjunctival staining was seen at 14 and 28 days.

Conclusions::

This first-in-human study of Lacripep in patients with primary Sjögren 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.

2022-08-01·Cell reports

A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration

Article

作者: Chen, Feeling Yu Ting ; McNamara, Nancy A ; Cheong, Ka Neng ; Knox, Sarah M ; Gaylord, Eliza A ; Efraim, Yael

Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein Lacripep reverses the pathological outcomes of dry eye through restoring the extensive network of corneal nerves that are essential for tear secretion, barrier function, epithelial homeostasis, and wound healing. 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.

2022-05-01·FASEB JOURNAL

Novel GPR87/SDC‐1 Complex Modulates Lacritin Rescue of Homeostasis

Article

作者: Adli, Mazhar ; Laurie, Gordon W. ; Doench, John ; Dias Teixeira, Karina

Introduction:

Ocular tears refract 80% of light and are essential for epithelial homeostasis. 7% of the world’s population suffer from tear insufficiency associated with compromised visual acuity and chronic ocular surface inflammation. Lacritin, a prosecretory mitogenic tear and plasma glycoprotein, restores homeostasis in a mouse dry eye model, and in human corneal epithelial cells (HCET) subjected to dry eye‐like IFNG and TNF stress. It does so by transiently accelerating epithelial autophagy (FOXO1/ATG7; FOXO3/ATG101) thereby restoring oxidative phosphorylation, as validated in a recent 204 patient phase 2 clinical trial of human Sjögren's Syndrome Dry Eye. Lacritin also promotes basal tearing by increasing the sensitivity of ion channel TRPM8 on corneal sensory nerves to tear drying. Here we report the identification of G protein‐coupled receptor 87 (GPR87) as the lacritin signaling receptor out of a genome‐wide CRISPR/Cas9 death screen using the C‐terminal lacritin synthetic peptide N‐94 as probe. GPR87 is expressed in the cornea and has a critical role in cellular proliferation and survival. Years ago, GPR87 was thought to be an LPA receptor, later disproven by Arfelt et al, ′17. Finally, we also report that GPR87 interacts with syndecan‐1 (SDC1), a cell surface co‐receptor for lacritin. We observed a direct binding of recombinant lacritin to GPR87, corroborating with the hypothesis that GPR87 is a critical receptor for lacritin homeostatic signaling.

Methods:

Validation studies of GPR87 were performed by generation of GPR87 knockdown cell lines by shRNA depletion by transducing HCE‐T cells with lentiviral GPR87 shRNA and non‐target controls. Depletion of GPR87 protein level was confirmed by western blot. Complementation assays were performed by transducing depleted HCE‐T’s with lentiviral GPR87 mouse cDNA. Lacritin affinity binding to GPR87 was first studied out of recombinant lacritin‐ or lacritin C‐25‐intein pulldowns. Truncation mutant ‘C‐25’, lacks lacritin's ‘N‐94’ bioactive domain. Lacritin pulldowns were challenged using each of eleven synthetic peptides corresponding to or together spanning all eight extracellular or intracellular strands or loops of GPR87 ‐ each at increasing concentrations (20, 100, 400 µM). To explore whether GPR87 can couple with SDC1, we blotted for GPR87 out of SDC‐1 pulldowns from HEK2936E cells co‐transfected with wild type or mutated GPR87 and SDC1 cDNA’s.

Results:

Lacritin, but not C‐25, binds GPR87 via GPR87's outer three loops with outer loop 3 peptide most inhibitory. GPR87 complexes with SDC1 in the absence of N‐94, but not with SDC1 lacking the PDZ binding domain nor with GPR87 lacking the G‐protein binding site “DRY” motif. SDC‐1 lacking N‐terminal domain heparan sulfate at S15 or membrane proximal chondroitin sulfate at S184 and S185 failed to bind GPR87. SDC‐1 also failed to complex with GPR87 in cells treated with chlorate to suppress sulfation.

Conclusions:

Lacritin appears to bind directly to the outer loop domains of GPR87 as part of a preformed SDC1‐GPR87 complex ‐ the latter linked in part by glycosaminoglycans and apparently by cytoplasmic SDC1 and GPR87 domains to regulate ocular surface health.

项与 Lacripep 相关的新闻（医药）

2024-11-21

·GlobeNewswire-Health Care

TearSolutions, Inc. Secures $3M Series B Funding

New Capital Boosts Efforts to Address Rare Corneal Disease Funding Highlights Growing Interest in Untapped Rare Corneal Conditions CHARLOTTESVILLE, Va., Nov. 21, 2024 (GLOBE NEWSWIRE) -- TearSolutions, Inc., a privately held biotech company developing potentially disruptive therapies for the treatment of ocular surface related diseases, today announced the successful closure of a $3M Series B round designed to accelerate its development programs for rare corneal diseases at both pre-clinical and clinical stages. "This round of financing is significant for several reasons, but most notably, it enables us to explore the potential of our therapeutic's highly differentiated mechanism of action in additional attractive corneal indications," said Anil Asrani, President and CEO of TearSolutions. "Moreover, this funding allowed us to convert existing debt, strengthening the Company's financial position as we look ahead." About TearSolutions, Inc. TearSolutions is a privately held biotechnology company focused on the discovery, development and commercialization of novel therapies for the treatment of patients with Ocular Surface Disease (OSD). The Company is based in Charlottesville, VA and is currently developing bioactive proprietary peptide proteoforms of lacritin. More information is available at www.tearsolutions.com. About LacripepTMLacripep was patented by Dr. Gordon Laurie, a professor of Ophthalmology and Cell Biology at the University of Virginia, based on his groundbreaking NIH funded research into the composition of human tears, which led to the discovery of lacritin. Lacritin and Lacripep represent a unique treatment modality that optimizes all three layers of the tear film while restoring corneal health and homeostasis. The intellectual property is exclusively licensed to TearSolutions, Inc. from the University of Virginia Licensing and Ventures Group. Corporate Contact: Anil Asrani, CEO aasrani@tearsolutions.com Source: TearSolutions, Inc.

2024-04-03

·GlobeNewswire-Health Care

TearSolutions, Inc. Appoints Louis M Alpern, MD, MPH, FACS, FICS to its Board of Directors

Dr. Alpern brings extensive clinical trialing experience in ophthalmologyCHARLOTTESVILLE, Va., April 03, 2024 (GLOBE NEWSWIRE) -- TearSolutions, Inc., a privately held biotech company developing potentially disruptive therapies for the treatment of Dry Eye Disease (DED) and other ocular surface related diseases, today announced that Louis M Alpern, MD, MPH, FACS, FICS has been appointed to the Company’s Board of Directors. “Dr. Alpern brings extensive real-world clinical experience treating patients with ocular surface disease, having prescribed or trialed virtually every dry eye treatment available,” said Anil Asrani, President and CEO of TearSolutions. “Dr. Alpern has served as a Principal Investigator in over 100 ophthalmology clinical trials and we welcome his valued perspectives as we continue to advance our clinical programs.” “I’ve seen, first-hand, the devastating impact that ocular surface disease can have on patients and their families and, as their treating physician, I shared in their frustration with currently available treatment options and the well-known problems associated with them,” said Dr. Alpern. “Given TearSolutions’ approach, the scientific rigor behind the discovery and development of their lacritin-derived peptide therapeutics and the pre-clinical and clinical data that they have generated, I believe that Lacripep has the potential to be a first-line treatment that will be broadly lauded by patients and their care-providers.” Dr. Alpern has more than four decades of private practice and clinical trialing experience in ophthalmology. He received his Doctor of Medicine from Harvard Medical School and his Master of Public Health from the Harvard School of Public Health. About TearSolutions, Inc. TearSolutions is a privately held biotechnology company focused on the discovery, development and commercialization of novel therapies for the treatment of patients with Ocular Surface Disease (OSD). The Company is based in Charlottesville, VA and is currently developing bioactive proprietary peptide proteoforms of lacritin, for chronic treatment of the signs and symptoms of dry eye disease (DED) associated with OSD. More information is available at www.tearsolutions.com. About LacripepTMLacripep was patented by Dr. Gordon Laurie, a professor of Ophthalmology and Cell Biology at the University of Virginia, based on his groundbreaking NIH funded research into the composition of human tears, which led to the discovery of lacritin. Lacritin and Lacripep represent a unique treatment modality that optimizes all three layers of the tear film while restoring corneal health and homeostasis. The intellectual property is exclusively licensed to TearSolutions, Inc. from the University of Virginia Licensing and Ventures Group. Corporate Contact: Anil Asrani, CEO aasrani@tearsolutions.com Source: TearSolutions, Inc.

高管变更

2023-11-01

·GlobeNewswire-Health Care

TearSolutions, Inc. Appoints Robert Dempsey to its Board of Directors

Dempsey brings worldwide Ophthalmology leadership experience in driving successful drug developmentCHARLOTTESVILLE, Va., Nov. 01, 2023 (GLOBE NEWSWIRE) -- TearSolutions, Inc., a privately held biotech company developing potentially disruptive therapies for the treatment of Dry Eye Disease (DED) and other ocular surface related diseases, today announced that Robert Dempsey has been appointed to the Company’s Board of Directors. “Robert is a proven industry leader with extensive and highly relevant experience in Ophthalmology and DED,” said Anil Asrani, President and CEO of TearSolutions. “I am genuinely excited and honored to have Robert join our board, as we work together to bring next generation therapeutics to patients suffering from the maladies associated with ocular surface disease.” “I’m thrilled to work closely with the TearSoultions team to help advance their programs and take the Company to the next level,” said Robert Dempsey. “With their lead product’s highly differentiated and well-characterized mechanism of action, human clinical data illustrating speed of relief, safety, and a best-in-class tolerability profile, as well as the potential to work in a majority of patients, I believe we have a novel disease-modifying solution that can bring much needed relief to patients as well as their treating physicians.” Robert brings more than two decades of domestic and global leadership experience in the Ophthalmology space driving successful drug development in public and private sectors through efficient organizational structure and capital investments. His widespread experience in Ophthalmology stems from diverse leadership roles across commercial, business development, medical affairs, and venture-backed startups. Currently, Robert serves as the Chief Executive Officer at AsclepiX Therapeutics focused on advancing an integrin regulating peptide for posterior segment diseases. He joined Asclepix in 2019 after serving as the Chief Executive Officer for TearClear where he accelerated the business and commercial strategies including a successful Series B financing and positive FDA engagements. Prior to that, he served as the Global Head of Ophthalmology at Shire, then Takeda, responsible for one of the top ten largest biopharma M&A deals in 2019, the divestiture of Xiidra® (lifitegrast ophthalmic solution) 5%, to Novartis in June 2019 for up to $5.3B. About TearSolutions, Inc. TearSolutions is a privately held biotechnology company focused on the discovery, development and commercialization of novel therapies for the treatment of patients with Ocular Surface Disease (OSD). The Company is based in Charlottesville, VA and is currently developing bioactive proprietary peptide proteoforms of lacritin, for chronic treatment of the signs and symptoms of dry eye disease (DED) associated with OSD. More information is available at www.tearsolutions.com. About Lacripep™Lacripep was patented by Dr. Gordon Laurie, a professor of Ophthalmology and Cell Biology at the University of Virginia, based on his groundbreaking NIH funded research into the composition of human tears, which led to the discovery of lacritin. Lacritin and Lacripep represent a unique treatment modality that optimizes all three layers of the tear film while restoring corneal health and homeostasis. The intellectual property is exclusively licensed to TearSolutions, Inc. from the University of Virginia Licensing and Ventures Group. Corporate Contact: Anil Asrani, CEO aasrani@tearsolutions.com Source: TearSolutions, Inc.

高管变更并购

100 项与 Lacripep 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
原发性干燥综合征	临床2期	美国	TearSolutions, Inc.	2017-06-30
神经营养性角膜炎	临床前	美国	TearSolutions, Inc.	2024-12-18

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03226444 (ARVO2021)	临床2期	原发性干燥综合征	204	0.005% Lacripep™	淵遞艱壓膚構鑰積遞鏇(淵選廠糧淵衊艱餘願襯) = 廠選築願淵廠選繭獵願構簾遞繭鏇範繭遞鹽艱 (膚製範壓繭淵齋鹽壓壓, 0.0024) 更多	-	2021-06-01
ARVO2015	N/A	干眼综合征	-	PBS	範鑰膚夢餘廠鏇選製鑰(餘夢蓋夢餘選築觸簾廠) = 淵築顧築網鹽繭獵網鑰遞淵構構選選築觸選蓋 (鏇範糧醖齋壓蓋簾醖廠 )	-	2015-06-01
ARVO2015	N/A	干眼综合征	-	Lacripep	範鑰膚夢餘廠鏇選製鑰(餘夢蓋夢餘選築觸簾廠) = 顧願遞鑰齋蓋壓願醖鏇遞淵構構選選築觸選蓋 (鏇範糧醖齋壓蓋簾醖廠, 5.47 ~ 12.2)	-	2015-06-01