timbetasin ophthalmic (RGN-259) / ReGenTree, RegeneRx - LARVOL DELTA

HLB Therapeutics Meets Target Patient Count for NK Treatment European Clinical Trial [Google translation] (HIT News) - "HLB Therapeutics....announced on the 10th that it met the target number of patients in the European Phase 3 clinical trial (SEER-3) of its neurotrophic keratitis (NK) treatment 'RGN-259' being conducted through its US subsidiary ReGenTree." "

Enrollment closed • Ophthalmology

Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2 (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: ReGenTree, LLC | Trial completion date: Feb 2024 ➔ Nov 2024 | Trial primary completion date: Nov 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

Thymosin beta 4: A potential novel adjunct treatment for bacterial keratitis. (PubMed, Int Immunopharmacol) - "Our previous work has shown that topical Tβ4 as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages) while enhancing bacterial killing and wound healing pathway activation in an experimental model ofP...Adjunctive thymosin beta 4 treatment holds novel therapeutic potential to regulate and, optimally, resolve disease pathogenesis in the cornea and perhaps other infectious and immune-based inflammatory disease. We plan to establish the importance of thymosin beta 4 as a therapeutic agent in conjunction with antibiotics with high impact for immediate clinical development."

Journal • Cataract • Corneal Abrasion • Dry Eye Disease • Infectious Disease • Inflammation • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Transplantation • TMSB4X

Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2 (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: ReGenTree, LLC | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2022 ➔ Mar 2023

Enrollment open • Trial initiation date • Dry Eye Disease • Ophthalmology

0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial. (PubMed, Int J Mol Sci) - "No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients."

Journal • P3 data • Dry Eye Disease • Ophthalmology

RegeneRx Licensee Submits Special Protocol Assessment to FDA for 4th Phase 3 Clinical Trial for Dry Eye Disease (PRNewswire) - “RegeneRx Biopharmaceuticals, Inc…is reporting today that its U.S. joint venture (JV) partner and licensee, HLB Therapeutics (HLBT), has announced that it submitted a request for the Special Protocol Assessment (SPA) to the U.S. FDA for an in-depth discussion and assessment of the clinical protocol for a fourth phase 3 clinical trial (ARISE-4) for the treatment of dry eye disease. RGN-259 is a sterile, preservative-free, eyedrop being developed by ReGenTree, a U.S. joint venture company between RegeneRx Biopharmaceuticals and HLB Therapeutics....‘Considering the initiation of this process, we expect that the ARISE-4 trial will begin around the second quarter of 2023,’ according to HLB Therapeutics.”

New P3 trial • Special protocol assessment • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2 (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: ReGenTree, LLC

New P3 trial • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (clinicaltrials.gov) - P3 | N=700 | Completed | Sponsor: ReGenTree, LLC | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

SEER-1 Demonstrates Safety and Efficacy of RGN-259 for Neurotrophic Keratopathy (AAO 2021) - "No treatment emergent adverse events led to study discontinuation. Conclusions In a small study, the efficacy and safety of RGN-259 validate that RGN-259 represents a potential first-line therapy for NK."

Clinical • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (clinicaltrials.gov) - P3; N=700; Active, not recruiting; Sponsor: ReGenTree, LLC; Trial completion date: Apr 2021 ➔ Dec 2021

Clinical • Trial completion date • Dry Eye Disease • Ophthalmology

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

"$RGRX RegeneRx JV Updates RGN-259 Regulatory Progress for Dry Eye Syndrome https://t.co/a9G4uBJPeq" (@otcdynamics)

Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (clinicaltrials.gov) - P3; N=700; Active, not recruiting; Sponsor: ReGenTree, LLC; Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

"$RGRX RegeneRx Comments on ARISE-3 Clinical Trial https://t.co/IxdqosJV0h" (@otcdynamics)

Clinical

Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (clinicaltrials.gov) - P3; N=700; Recruiting; Sponsor: ReGenTree, LLC; Trial primary completion date: Aug 2020 ➔ Nov 2020

Clinical • Trial primary completion date • Dry Eye Disease • Ophthalmology

RegeneRx Expects to Complete Short-Term Financing While Awaiting Completion of Phase 3 Clinical Trial for Dry Eye Syndrome (PRNewswire) - "RegeneRx Biopharmaceuticals...announced that it has verbally agreed to a short-term financing transaction with one of its major stockholders, and members of its board of directors and management. The funding will provide working capital through the first quarter of 2021 and while we await the completion of our phase 3 dry eye clinical trial (ARISE-3) expected later this year."

Enrollment status • Financing • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy : SEER-1 (clinicaltrials.gov) - P3; N=18; Terminated; Sponsor: ReGenTree, LLC; N=46 ➔ 18; Trial completion date: Sep 2020 ➔ Mar 2020; Recruiting ➔ Terminated; Trial primary completion date: Aug 2020 ➔ Nov 2019; Business decision

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Anesthesia • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (clinicaltrials.gov) - P3; N=700; Recruiting; Sponsor: ReGenTree, LLC; Trial completion date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Apr 2020 ➔ Aug 2020

Clinical • Trial completion date • Trial primary completion date • Conjunctivitis • Dry Eye Disease • Ophthalmology

No effect of thymosin beta-4 on the expression of the transcription factor Islet-1 in the adult murine heart. (PubMed, Pharmacol Res Perspect) - "TB4 did not induce LacZ positivity in ventricular explants cultures of Isl1-nLacZ mice nor did it affect the density of LacZ cells in explant cultures of nLacZ regions of the heart. In summary, we found no evidence that TB4 reactivates Islet-1 expression in adult mouse ventricle."

Journal • Acute Coronary Syndrome • Biosimilar • Cardiovascular

World Health Organization recommends INN for thymosin beta 4 as 'timbetasin' (RegeneRx Press Release) - "RegeneRx...announced that the recommended INN...for Thymosin Beta 4 is timbetasin, as published by the World Health Organization...Any drug substance that has the characteristics of 'Thymosin beta 4' that will be developed as a pharmaceutical product in the future must use the name 'timbetasin', a term requested by GtreeBNT."

Clinical • Dry Eye Disease • Ophthalmology

Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy : SEER-1 (clinicaltrials.gov) - P3; N=46; Recruiting; Sponsor: ReGenTree, LLC; Trial completion date: Nov 2018 ➔ Aug 2019; Trial primary completion date: Sep 2018 ➔ May 2019

Trial completion date • Trial primary completion date • Anesthesia • Biosimilar • Dry Eye Disease • Ophthalmology

Potential role of thymosin beta 4 in the treatment of nonalcoholic fatty liver disease. (PubMed, Chronic Dis Transl Med) - "However, no research has been done to investigate the effects of Tβ4 on NAFLD. Based on the findings above mentioned, we hypothesize that Tβ4 may represent an effective treatment for NAFLD."

Journal • Review • Biosimilar • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Metabolic Disorders • Non-alcoholic Steatohepatitis • Obesity • Oncology • Solid Tumor

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress. (PubMed) - "...The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin...These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development."

Journal • Biosimilar • Cardiovascular • Immunology • Reperfusion Injury

Characterization of the protein components of matrix stones sheds light on the S100-A8 and A9 relevance in the inflammatory pathogenesis of these rare renal calculi. (PubMed) - J Urol - "The abundance of inflammatory molecules identified points to an inflammatory process being the event that initializes soft calculi formation, rather than a consequence. The post-translational oxidative changes in S100-A8 and A9, and the presence of Thymosin beta-4, Granulins and Ubiquitin also suggest the intervention of host defenses through a superimposed vigorous counter-inflammatory process. The post-translational changes seen in the proteins and peptides, and the known self-assembling capability of S100-A8 and A9 probably explain the gelatinous consistency of these stones."

Journal • Biosimilar

RGN-259: FDA meeting related to NDA submission for dry eye syndrome in 2019 (Regenerx) - 2018 Annual Meeting

FDA event • Dry Eye Disease • Ophthalmology