This study will examine the safety and efficacy of NPI-001 Tablets as compared to placebo for 24 months in subjects with vision loss due to RP associated with Usher syndrome.

Start Date03 Sep 2020

Sponsor / Collaborator

Nacuity Pharmaceuticals, Inc.Startup

[+1]

100 Clinical Results associated with Nacuity Pharmaceuticals, Inc.

0 Patents (Medical) associated with Nacuity Pharmaceuticals, Inc.

Literatures (Medical) associated with Nacuity Pharmaceuticals, Inc.

01 Nov 2024·Experimental Eye Research

N-acetylcysteine amide and di- N-acetylcysteine amide protect retinal cells in culture via an antioxidant action

Article

Author: Chidlow, Glyn ; Wall, G. Michael ; Wall, G Michael ; Wood, John P.M. ; Casson FRANZCO, Robert J. ; Wood, John P M ; Casson, Robert J

Reactive oxygen species (ROS) play a significant role in toxicity to the retina in a variety of diseases. N-acetylcysteine (NAC), N-acetylcysteine amide (NACA) and the dimeric di-N-acetylcysteine amide (diNACA) were evaluated in terms of protecting retinal cells, in vitro, in a variety of stress models. Three types of rat retinal cell cultures were utilized in the study: macroglial-only cell cultures, neuron-only retinal ganglion cell (RGC) cultures, and mixed cultures containing retinal glia and neurons. Ability of test agents to attenuate oxidative stress in all cultures was ascertained. In addition, capability of agents to protect against a variety of alternate clinically-relevant stressors, including excitotoxins and mitochondrial electron transport chain inhibitors, was also evaluated. Capacity of test agents to elevate cellular levels of reduced glutathione under normal and compromised conditions was also determined. NAC, NACA and diNACA demonstrated concentration-dependent cytoprotection against oxidative stress in all cultures. These three compounds, however, had differing effects against a variety of alternate insults to retinal cells. The most protective agent was NACA, which was most potent against the most stressors (including oxidative stress, mitochondrial impairment by antimycin A and azide, and glutamate-induced excitotoxicity). Similar to NAC, NACA increased glutathione levels in non-injured cells, although diNACA did not, suggesting a different, unknown mechanism of antioxidant activity for the latter. In support of this, diNACA was the only agent to attenuate rotenone-induced toxicity in mitochondria. NAC, NACA and diNACA exhibited varying degrees of antioxidant activity, i.e., protected cultured rat retinal cells from a variety of stressors which were designed to mimic aspects of the pathology of different retinal diseases. A general rank order of activity was observed: NACA ≥ diNACA > NAC. These results warrant further exploration of NACA and diNACA as antioxidant therapeutics for the treatment of retinal diseases, particularly those involving oxidative stress. Furthermore, we have defined the battery of tests carried out as the "Wood, Chidlow, Wall and Casson (WCWC) Retinal Antioxidant Indices"; we believe that these are of great value for screening molecules for potential to reduce retinal oxidative stress in a range of retinal diseases.

01 Sep 2023·Experimental Eye Research

N-Acetylcysteine amide (NACA) and diNACA inhibit H2O2-induced cataract formation ex vivo in pig and rat lenses

Article

Author: Lim, J C ; Martis, R M ; Wu, H ; Donaldson, P J ; Wall, G M ; Grey, A C

Oxidative stress plays a central role in cataract formation suggesting that antioxidants might slow cataract progression. The anticataract activity of N-acetylcysteine amide (NACA) and (2 R, 2 R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA) and/or N-acetylcysteine (NAC), were evaluated in porcine and rat lens models. Cataractogenesis via oxidation was induced with H₂O₂ and/or glucose oxidase (GO). Porcine lenses were incubated in 0.1 mM, 1 mM, or 10 mM NAC, NACA or diNACA for 24 h. Lenses were then transferred to media containing 0.75 mM H₂O₂ and 4.63U of GO in order to maintain a constant H₂O₂ level for an additional 8 h. At the end of incubation, lenses were imaged under darkfield microscopy. Separately, rat lenses were extracted from 3-week-old Wistar rats and incubated with either 10 mM NACA or 10 mM diNACA for 24 h prior to treatment with 0.2U GO to generate a steady source of ∼0.6 mM H₂O₂. Rat lenses were analyzed by LC-MS/MS to quantify changes in cysteine, cystine, glutathione (GSH) or oxidised glutathione (GSSG) levels in the lens epithelium, cortex or core. Pre-treatment with NACA or diNACA followed by oxidation with H₂O₂ and/or GO to stimulate cataract formation afforded rapid assessment in ex vivo porcine (32 h) and rat (48 h) lens models. Pre-treatment of isolated porcine lenses with 0.1 mM, 1 mM or 10 mM of either NAC, NACA or diNACA followed by H₂O₂/GO treatment resulted in reduced lens opacity relative to the lenses exposed to H₂O₂/GO, with NACA and diNACA reducing opacities to a greater extent than NAC. Rat lenses incubated with 10 mM NACA or 10 mM diNACA without exposure to H₂O₂ showed no signs of opacities. Pre-treatment of rat lenses with 10 mM NACA or 10 mM diNACA, followed by GO cataract induction resulted in reduced opacities compared to control (GO alone). LC-MS/MS analyses revealed that NACA, but not diNACA, increased cysteine, cystine and GSH levels in rat lens epithelium and cortex regions. Taken together, both NACA and diNACA inhibited cataract formation to a greater extent than NAC (all at 1-10 mM) in an ex vivo porcine lens model. Both NACA and diNACA (both at 10 mM) reduced cataract formation in rat lenses. Based on LC-MS/MS analyses, NACA-induced reduction in opacity observed in rat lenses was attributed to enhanced cysteine and GSH levels while the diNACA-induced reduction in opacity induced did not consistently increase cysteine, cystine and GSH levels and, therefore, appears to involve a different antioxidant mechanism. These screening studies warrant further testing of NACA and diNACA as anticataract agents.

01 Dec 2022·Orphanet Journal of Rare Diseases

Evaluation of NACA and diNACA in human cystinosis fibroblast cell cultures as potential treatments for cystinosis

Article

Author: Cairns, Donald ; Michael Wall, G ; Hector, Emma

AbstractBackgroundCystinosis is a rare autosomal recessive lysosomal storage disease, associated with high morbidity and mortality. Mutations in the CTNS gene disable a membrane protein responsible for the transport of cystine out of the lysosome. Loss of transporter function leads to intralysosomal cystine accumulation and long-term damage to various tissues and organs, including the kidneys, eyes, liver, muscles, pancreas, and brain. The only cystine-depletion therapy for treatment of cystinosis is cysteamine which requires frequent administration of high doses and often causes gastrointestinal pain as well as pungent sulfurous odor in patients. The current in vitro study evaluated antioxidants, N-acetylcysteine amide (NACA; NPI-001) and (2R,2R′)-3,3′-disulfanediyl bis(2-acetamidopropanamide) (diNACA; NPI-002), as potential treatments for cystinosis.MethodsCytotoxicity of cysteamine, NACA and diNACA was evaluated in cultured human cystinotic fibroblasts (HCFs). HCFs were cultured in 96 well plates incubated for 0–72 h in the presence of 25, 50 or 75 μM each of either cysteamine, NACA or diNACA along with an untreated control. Media was removed and cell viability assessed. Next, cystine-depleting activities of cysteamine, NACA and diNACA were screened in HCFs cell culture utilizing an inexpensive, proven colorimetric assay. HCFs were seeded and allowed to reach approximately 80% confluence before the addition of the test articles: 50 μM of either cysteamine, NACA or diNACA in media along with an untreated control. HCFs were incubated, harvested, and cystine was reduced to cysteine, the concentration of which was then determined per quantity of protein compared to a cysteine standard. Statistically significant cystine depletion was determined by paired t-test versus untreated control (p < 0.05).ResultsNeither cysteamine, NACA nor diNACA at 25, 50 or 75 μM caused cytotoxicity in HCFs. Treatment with all tested concentrations (25, 50 or 75 µM) of either NACA or diNACA at 48 or 72 h resulted in statistically significant increases in cell viability, relative to untreated control, whereas the higher concentrations (50 or 75 µM) of cysteamine achieved statistical significance at both timepoints but not the lowest concentration (25 µM). All test articles depleted cystine from HCFs compared to control. NACA depletion of cystine was statistically superior to cysteamine at 6, 24 and 48 h and numerically greater at 72 h. DiNACA depletion of cystine was statistically superior to cysteamine at 6 and 48 h, slightly numerically greater at 24 h and slightly less at 72 h.ConclusionsNACA and diNACA were non cytotoxic to HCFs and significantly increased cell viability. Cystine reduction was determined as percent of control after incubation with 50 µM of NACA, diNACA or cysteamine in HCFs cell culture for 6, 24, 48 and 72 h. Of the three test articles, NACA exhibited most rapid and greatest potency in cystine reduction. Rank order potency for cystine reduction over time was observed, NACA > diNACA ≥ cysteamine. Therefore, further study of NACA and diNACA as potential treatments for cystinosis is warranted.

News (Medical) associated with Nacuity Pharmaceuticals, Inc.

03 May 2024

·www.prnewswire.com

RevOpsis Welcomes Dr. Emmett Cunningham to Strategic Advisory Board

Internationally renowned ophthalmologist and investment leader joins to support advancement of disruptive ophthalmic treatments SAN CARLOS, Calif., May 3, 2024 /PRNewswire/ -- RevOpsis Therapeutics, a next-generation biopharmaceutical company spearheading innovation in ophthalmic therapies, announced today the appointment of Dr. Emmett Cunningham to its Strategic Advisory Board (SAB) and as a private investor. Dr. Cunningham, a distinguished figure in the ophthalmic and investment communities, brings more than twenty years of experience as a full-time entrepreneur and investor to his new role with RevOpsis. Continue Reading "I am honored to join RevOpsis as an early investor and Strategic Advisory Board member." said Dr. Emmett Cunningham. Post this Dr. Emmett Cunningham, RevOpsis Strategic Advisory Board member Dr. Cunningham is currently Senior Partner at HealthQuest Capital Management. Prior, he most recently served as a Senior Managing Director at Blackstone Life Sciences group (BXLS) of Blackstone, Inc. (BX), through the acquisition of Clarus Ventures in 2018, where he was a member of the full-time investment team since Clarus' inception in 2006. "I am honored to join RevOpsis as an early investor and Strategic Advisory Board member. My experience is well aligned to contribute to the RevOpsis mission of revolutionizing ophthalmic therapies," said Dr. Emmett Cunningham. "I am impressed by the company's dedication to innovation and commitment to improving patient care. I look forward to collaborating with the team to drive their pipeline of transformative treatments forward." With a career spanning notable roles at leading investment firms, Dr. Cunningham's expertise in guiding successful investments in biotechnology companies is unparalleled. His track record includes significant contributions to the development and FDA approval of ten therapeutics, with an additional therapeutic pending FDA submission. His visionary leadership and strategic insights have played a pivotal role in shaping the landscape of ophthalmic therapies, driving innovation, and fostering growth within the industry. Dr. Cunningham's prestigious career includes several prominent board memberships with various noteworthy biopharmaceutical companies including several ophthalmology focused companies such as Annexon Biosciences, GrayBug Vision, Nacuity Pharmaceuticals, and Eyconis, where he is co-founder and executive chair. "We are excited to welcome Dr. Emmett Cunningham to our Strategic Advisory Board," said RevOpsis interim CEO Dr. Ram Bhandari. "Dr. Cunningham's wealth of experience and deep understanding of the ophthalmic and investment landscapes make him an invaluable asset to the RevOpsis SAB. Dr. Cunningham's guidance will be instrumental as we continue to advance our proprietary Rev-Mod Platform and develop novel treatments for chronic multifactorial diseases, including our current lead candidate RO-104." In addition to his remarkable achievements in the investment sector, Dr. Cunningham is widely recognized as an internationally renowned specialist in infectious and inflammatory eye diseases. He has authored over 400 publications and made significant contributions to advancing the understanding and treatment of vision-related disorders. About RO-104 Leveraging the proprietary Rev-Mod platform, RO-104 is RevOpsis' current lead candidate. Engineered as a first-in-class fully human modular tri-specific biologic designed to address all three clinically validated dominant angiogenic pathways (VEGF-A, VEGF-C, Ang-2) implicated in retinal vascular disease progression, including neovascular age-related macular degeneration (nAMD). RO-104 represents a significant innovative advancement in the treatment landscape for retinal vascular diseases. Backed by a significant body of preclinical evidence demonstrating intended efficacy and safety in established animal models, RO-104 heralds a transformative approach positioned to redefine the current standard of care for patients with nAMD. About Rev-Mod Platform The proprietary Rev-Mod Platform employs a modular 'plug-and-play' approach to streamline and expedite the efficient discovery and development of multispecific biologics targeting a wide spectrum of chronic, prevalent, large diseases, that are the leading causes of death and disability worldwide. Our proprietary platform boasts a vast library of nearly 30 billion fully human antibody components in a structured phage display system, facilitating rapid identification and assembly of multispecific product candidates. With seamless compatibility, the Rev-Mod platform enables swift and efficient design of multispecific biologics to address unmet needs in major therapeutic areas including ophthalmology, oncology, and immune-mediated diseases. About RevOpsis Therapeutics Founded in 2018, RevOpsis Therapeutics is a privately held, next-generation biopharmaceutical company spearheading innovation in ophthalmic therapies. Guided by a team of leading physicians, scientists, and business leaders, we are dedicated to leveraging our proprietary Rev-Mod Platform to develop and commercialize groundbreaking treatments for chronic multifactorial diseases. With a steadfast commitment to responsibly advancing patient care, we aim to usher in a new era of improved disease management and extended disease remission. For more information, please visit . SOURCE RevOpsis

Executive Change

30 Apr 2024

·www.globenewswire.com

Nacuity Pharmaceuticals Announces First Patients Implanted in Final Cohort of Phase 1/2 Clinical Trial Evaluating NPI-002 Intravitreal Implant for the Delay of Cataract Progression

Two patients have been implanted in the final cohort of the trial Final cohort is actively enrolling adult patients undergoing vitrectomy FORT WORTH, Texas, April 30, 2024 (GLOBE NEWSWIRE) -- Nacuity Pharmaceuticals, Inc., a clinical stage biopharmaceutical company developing treatments for retinitis pigmentosa, cataracts and other ocular diseases caused by oxidative stress, today announced that the first patients have been implanted in the final cohort of the Phase 1/2 clinical trial evaluating NPI-002 for delayed cataract progression in patients undergoing vitrectomy. An independent Data Safety Monitoring Board (DSMB) recommended proceeding with the final cohort after a positive safety review, which was subsequently approved by the overseeing Human Research Ethics Committee. NPI-002 is a proprietary antioxidant molecule delivered via a sustained release intravitreal implant. The Phase 1/2 NP-2 trial is a randomized, controlled, masked clinical trial assessing the safety and efficacy of NPI-002 in delaying cataract progression in adult patients undergoing vitrectomy. “Patients typically need cataract surgery within a year of their vitrectomy,” said Robert Casson, MBBS (Hons), DPhil, principal investigator of the trial and Professor, Royal Adelaide Hospital. “Delaying a subsequent cataract surgery after vitrectomy can alleviate the stress of having two ocular surgeries in a short period of time and improve surgical outcomes for patients.” The final cohort of the trial is actively enrolling patients for clinical sites at The Royal Adelaide Hospital (RAH) in Adelaide, South Australia, and personalEYES in Parramatta, New South Wales, Australia. “We’re encouraged by the positive safety signals seen to date and we’re grateful for the trial’s progression thanks to the diligent work of the trial investigators and the participation of patients,” said Halden Conner, Chairman, CEO, and Co-Founder of Nacuity Pharmaceuticals. “We look forward to continuing our evaluation of our NPI-002 antioxidant to slow cataract progression and preserve the sight of these patients.” For more information about the Phase 1/2 clinical trial of NPI-002, please visit clinicaltrials.gov (Identifier: NCT05026632). About NPI-002NPI-002 is a novel, differentiated, slow-release, small molecule being developed to slow cataract progression. For the treatment of cataract, a sterile intravitreal implant containing NPI-002 has been developed, along with a precision delivery system. In vitro and in vivo studies showed vitreal elution over time and revealed no cytotoxicity with NPI-002. In ex-vivo rat and porcine lenses, NPI-002 inhibited oxidative-induced cataracts. NPI-002 is currently being evaluated in a Phase 1/2 proof-of-concept clinical trial in Australia (NCT05026632). About Nacuity PharmaceuticalsNacuity Pharmaceuticals is a clinical-stage leader in innovative treatments for oxidative stress. The company’s powerful, targeted therapies aim to attenuate oxidative tissue damage, a driver of blinding eye diseases and a broad spectrum of serious chronic conditions. Nacuity has three highly differentiated clinical programs ongoing in retinitis pigmentosa, cataract and inherited cystinosis. Nacuity has operations in Fort Worth, TX, USA, and Australia, and extensive managerial and scientific domain expertise as well as backing from Foundation Fighting Blindness (https://www.fightingblindness.org/) and its venture arm RD Fund (https://www.retinaldegenerationfund.org). For more information, please visit www.nacuity.com. Media ContactJulia Clements267.626.1085jclements@6degreespr.com

Clinical Study

16 Apr 2024

·www.globenewswire.com

Nacuity Pharmaceuticals Expands Board of Directors with Appointment of Dr. Emmett Cunningham, Jr.

Ophthalmology industry veteran brings 20 years of experience as a life science investor and entrepreneur to Nacuity’s boardFORT WORTH, Texas, April 16, 2024 (GLOBE NEWSWIRE) -- Nacuity Pharmaceuticals, Inc., a clinical stage biopharmaceutical company developing novel treatments for retinitis pigmentosa, cataract, and other diseases caused by oxidative stress, today announced the appointment of Emmett T. Cunningham, Jr., M.D., Ph.D., MPH, to its board of directors. Dr. Cunningham is currently a Senior Partner at HealthQuest Capital Management and co-founder and Executive Chairman of Eyconis, Inc., a spinout of Ascendis Pharma created to develop, manufacture, and commercialize TransCon ophthalmology assets globally. “We’re thrilled to welcome Dr. Cunningham to our board of directors,” said Halden Conner, Chairman, CEO and Co-Founder of Nacuity Pharmaceuticals. “His career as a prominent leader in the ophthalmology industry, bridging the business world and ophthalmic innovation, will be a vital asset at this pivotal time for our clinical programs in oxidative stress.” Dr. Cunningham is an ophthalmology industry veteran with over 20 years of experience as a full-time investor and entrepreneur who has led or co-led investments and partnerships in the medical device and biotechnology space that have supported the FDA approval of multiple therapeutics. He is also an internationally recognized specialist in infectious and inflammatory eye disease with over 400 publications. “Nacuity’s approach to treating ophthalmic and non-ophthalmic disorders is both completely novel and tremendously promising,” said Dr. Cunningham. “I look forward to working with the Nacuity team to unlock the broad therapeutic potential of its clinical programs in treating ocular and non-ocular disease.” Prior to HealthQuest and Eyconis, Dr. Cunningham served as a Senior Managing Director at Blackstone, Inc. following that firm’s acquisition of Clarus Ventures in 2018. At Clarus, Dr. Cunningham was a member of the full-time investment team since the firm’s inception in 2006. From 2001 to 2005, Dr. Cunningham was the Senior Vice President of Medical Strategy at Eyetech Pharmaceuticals, Inc., where he was part of the leadership team that developed Macugen®, a first-in-class VEGF-A inhibitor for the treatment of age-related macular degeneration. Prior to Eyetech, Dr. Cunningham was at Pfizer, Inc. In addition, Dr. Cunningham was the co-founder and chairman of the Ophthalmology Innovation Summit (OIS). He received an M.D. and MPH in epidemiology and statistics from Johns Hopkins University and a Ph.D. in neuroscience from the University of California at San Diego for work done at The Salk Institute. Dr. Cunningham is a member of the board of directors of Galera Therapeutics and Executive Chairman of Eyconis. He serves as Innovator in Residence for Johns Hopkins Technology Ventures (JHTV); as a member of the Biomedical Engineering Advisory Board at Johns Hopkins University; is an advisor to the Byers Center for BioDesign at Stanford University; and serves philanthropically on the Boards of The Alta Foundation and EverythingALS. About Nacuity Pharmaceuticals, Inc. Nacuity Pharmaceuticals, Inc. (https://www.nacuity.com/), is a clinical-stage leader in innovative treatments for diseases produced by oxidative stress. The company’s powerful, targeted therapies aim to attenuate oxidative tissue damage, a driver of blinding eye diseases and a broad spectrum of serious chronic conditions. Nacuity has three highly differentiated, first-in-class clinical development programs ongoing in retinitis pigmentosa, cataract and inherited cystinosis. Nacuity has operations in Fort Worth, TX, USA, and Australia, and extensive managerial and scientific domain expertise as well as backing from Foundation Fighting Blindness (https://www.fightingblindness.org/) and its venture arm RD Fund (https://www.retinaldegenerationfund.org). Nacuity Media ContactJulia Clements267.626.1085jclements@6degreespr.com

Executive ChangeAcquisition

100 Deals associated with Nacuity Pharmaceuticals, Inc.

100 Translational Medicine associated with Nacuity Pharmaceuticals, Inc.

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Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

NPI-001	Usher Syndromes More	Phase 2 Clinical
NPI-002	Cataract More	Phase 2 Clinical
NPI-00X	Eye Diseases More	Discontinued
NP-4	Cystinosis More	Pending
NP-3	Cystinosis More	Pending

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