Highlights Favorable Security Profile of the Oral New Chemical Entity APX3330 and Its Novel Anti-Angiogenic and Anti-Inflammatory Mechanism of Motion Properties Related to a Broad Vary of Retinal Ailments
Part 2 Information from ZETA-1 Trial in Diabetic Retinopathy Anticipated in 2022
FARMINGTON HILLS, Mich., July 22, 2021 (GLOBE NEWSWIRE) — Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical firm targeted on creating and commercializing therapies for the remedy of a number of eye issues, at this time introduced the publication of a commentary article within the Journal of Mobile Signaling that includes its Ref-1 Inhibitor, APX3330, for the remedy of retinal illness. The article is titled “APE1/Ref-1 as a Novel Goal for Retinal Illness”.
The Journal of Mobile Signaling is an open-access peer reviewed journal which options articles on newest analysis findings and views on mobile and molecular signaling – a vital course of that orchestrates and integrates varied organic features by means of a number of signaling cascades and effector molecules. The article could be accessed on-line on the following hyperlink: Welcome to Scientific Archives | APE1/Ref-1 as a Novel Target for Retinal Diseases.
“We’ve now printed over 21 peer-reviewed articles on APX3330 and over 70 articles on the APE1/Ref-1 goal in varied journals, with 5 publications particularly associated to retinal illness,” mentioned Mark R. Kelley, PhD, Professor within the Division of Pediatrics and Glick Eye Heart at Indiana College Faculty of Medication and member of Ocuphire’s Medical Advisory Board. “This printed commentary article discusses the great information on each Ref-1 as a novel retina goal in addition to our oral inhibitor, APX3330, predicted to achieve human retinal concentrations several-fold higher than the dose required to indicate efficacy in mice. APX3330 concurrently blocks key pathways concerned in angiogenesis and irritation processes, thereby conferring safety to the retina. APX3330 represents the Ref-1 program’s lead compound, with pipeline candidates APX2009 and APX2014 that might be formulated for intravitreal sustained launch supply.”
Highlights from the APE1/Ref-1 Evaluate Article:
- Ref-1 protein regulates a number of transcription elements regulating irritation and angiogenesis.
- As a Ref-1 inhibitor, APX3330 decreases each irregular angiogenesis and irritation by blocking activation of HIF-1a, which then results in diminished VEGF signaling and decrease manufacturing of pro-inflammatory cytokines akin to NF-kB, TNF-alpha, and STAT3.
- On the 300 mg oral twice per day dose getting used within the ongoing Part 2 medical trial in sufferers with diabetic retinopathy (DR), APX3330 is anticipated to achieve several-fold increased retinal Cmax, and many-fold concentrations above 15.4 ug/ml retinal AUC, than the efficacious dose of oral gavage 25 mg/kg twice per day given to mice within the L-CNV mannequin of retinal illness.
- In 5 Part 2 research involving over 300 sufferers, APX3330 given oral (systemically) was properly tolerated with no vital questions of safety recognized. No AE was noticed in ≥ 5% of sufferers handled with APX3330. Gentle rash and delicate diarrhea had been noticed in 1% of APX3330 handled sufferers and had been considered presumably drug-related.
- Ocuphire is presently recruiting for ZETA-1 Part 2 medical trial, which can enroll topics throughout 20 U.S. websites with the first endpoint of the share of topics with >2-step enchancment on the Diabetic Retinopathy Severity Scale rating.
The first endpoint for the ZETA-1 trial is the Early Therapy Diabetic Retinopathy Rating (ETDRS) diabetic retinopathy severity rating (DRSS). This rating is predicated on vascular abnormalities in retinal images, and a 2-step or extra enchancment on this rating is the accepted regulatory endpoint for the remedy of DR. Within the PANORAMA examine which examined the impact of the anti-VEGF drug EYLEA® on DRSS, this major endpoint was met with considerably extra sufferers responding to remedy in comparison with placebo after 24 weeks of 2mg dosing intravitreal each 16 weeks. Within the mouse L-CNV mannequin, the efficacy of oral APX3330 was just like EYLEA intravitreal injections. Taken along with the opposite security, PK, and preclinical information, this offers a powerful rationale for pursuing diabetic retinopathy within the ZETA-1 trial. Visible perform and central retinal thickness may even be measured given the anticipated efficacy in remedy of diabetic macular edema (DME).
“With its twin mechanism of motion focusing on pathogenic irritation downstream to Ref-1, we imagine APX3330 may symbolize an vital new therapeutic method in addressing quite a lot of ocular situations, together with as a single agent for diabetic retinopathy and as an adjunctive remedy to anti-VEGF in diabetic macular edema, moist age-related macular degeneration, and different retinal illnesses,” mentioned Mina Sooch, MBA, President and CEO of Ocuphire Pharma. “We’re lucky to construct on the previous 11 Part 1 and a couple of medical trials learning irritation in liver illnesses by Eisai and angiogenesis in oncology by Apexian. As our medical program surrounding Ref-1 inhibition continues to mature, we anticipate APX3330 to generate extra consideration forward of our Part 2 information readout in diabetic retinopathy anticipated subsequent 12 months.”
The progressive pathogenesis of retinal and choroidal illness usually entails vascular leakage, retinal ischemia, and the discharge of vasoproliferative development elements and inflammatory mediators. Earlier remedy choices to forestall or delay irreversible imaginative and prescient loss for sufferers with diabetic eye illness are essential. Though biologic therapies akin to Eylea (that are injections instantly into the attention) have been accepted within the subject, the invasive nature of remedy results in a reluctance by physicians to undertake bi-monthly power injection regimens throughout the early phases of illness development. Immediately, diabetic retinopathy stays intently monitored by retinal specialists however largely untreated. An alternate (oral) remedy modality presents immense potential for use as monotherapy for non-proliferative or early proliferative phases of diabetic retinopathy.
“As an oral pill with a positive security profile demonstrated within the early medical trials, APX3330 may provide a handy resolution for a big and rising international inhabitants of diabetes-related retinal illnesses,” mentioned Dr. Peter Kaiser, Professor of Ophthalmology on the Cole Eye Institute, Cleveland Clinic. “Extra importantly, APX3330 has the potential to scale back the burden of intravitreal injections on the sufferers.”
About Diabetic Retinopathy
Diabetes is the main explanation for blindness amongst adults aged 20 – 74. In america alone, over 7 million sufferers endure from diabetic retinopathy (DR), a complication of diabetes through which chronically elevated blood sugar ranges trigger harm to blood vessels within the retina. A further 750,000 sufferers endure from diabetic macular edema (DME), one of the frequent issues of diabetic retinopathy the place the macula swells from fluid leaked from broken blood vessels. The illness development of each DR and DME entails irregular vessel proliferation and irritation. Thus, present accepted remedies for DR and DME embody an over $10 billion international market and contain administering anti-VEGF injections (akin to EYLEA® by Regeneron, Lucentis® by Genentech, and Avastin® by Genentech) to lower vessel formation or steroids (akin to OZURDEX® by Abbvie/Allergan) to lower irritation into eyes with superior retinal illness. ZETA-1 is investigating the potential of APX3330 to supply an progressive and conveniently administered oral remedy for diabetic retinopathy that addresses each of those illness pathways.
About Ocuphire Pharma
Ocuphire is a publicly traded (NASDAQ: OCUP), clinical-stage ophthalmic biopharmaceutical firm targeted on creating and commercializing therapies for the remedy of a number of eye issues. Ocuphire’s pipeline presently contains two small-molecule product candidates focusing on back and front of the attention indications. The corporate’s lead product candidate, Nyxol® (0.75% phentolamine ophthalmic resolution) Eye Drops, is a once-daily preservative-free eye drop formulation of phentolamine mesylate, a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to scale back pupil measurement, and is being developed for a number of indications, together with dim mild or night time imaginative and prescient disturbances (NVD), reversal of pharmacologically-induced mydriasis (RM), and presbyopia, and has been studied in 9 medical trials together with the just lately accomplished Part 3 trial in RM and Part 2 trial in presbyopia. Ocuphire reported constructive topline information in March 2021 for MIRA-2, a Part 3 FDA registration examine for remedy of RM. Ocuphire additionally reported constructive top-line information in June 2021 for VEGA-1, a Part 2 trial for the remedy of presbyopia. Nyxol can be presently in Part 3 medical improvement for NVD. Ocuphire’s second product candidate, APX3330, is an oral pill designed to inhibit angiogenesis and irritation pathways related to retinal and choroidal vascular illnesses, akin to diabetic retinopathy (DR) and diabetic macular edema (DME) and has been studied in 11 Part 1 and a couple of trials. APX3330 is presently enrolling topics in a Part 2 medical trial in topics with DR/DME. As a part of its technique, Ocuphire will proceed to discover alternatives to accumulate further ophthalmic belongings and to hunt strategic companions for late-stage improvement, regulatory preparation, and commercialization of medicine in key international markets. Please go to www.clinicaltrials.gov to be taught extra about Ocuphire’s accomplished Part 2 trials, just lately accomplished Part 3 registration trial in RM (NCT04620213), just lately accomplished Part 2 trial in presbyopia (NCT04675151), ongoing Part 3 registration trial in NVD (NCT04638660), and Part 2 trial in DR/DME (NCT04692688). For extra data, please go to www.ocuphire.com.
Ahead Trying Statements
Statements contained on this press launch relating to issues that aren’t historic details are “forward-looking statements” throughout the that means of the Non-public Securities Litigation Reform Act of 1995. Such statements embrace, however usually are not restricted to, statements in regards to the anticipated timing of the Part 2 ZETA-1 medical trial in diabetic retinopathy, the potential formulation of APX2009 and APX2014, and the flexibility of APX3330 to symbolize an vital new therapeutic method in addressing quite a lot of ocular situations. These forward-looking statements are based mostly upon Ocuphire’s present expectations and contain assumptions that will by no means materialize or might show to be incorrect. Precise outcomes and the timing of occasions may differ materially from these anticipated in such forward-looking statements on account of varied dangers and uncertainties, together with, with out limitation: (i) the success and timing of regulatory submissions and pre-clinical and medical trials, together with enrollment and information readouts; (ii) regulatory necessities or developments; (iii) modifications to medical trial designs and regulatory pathways; (iv) modifications in capital useful resource necessities; (v) dangers associated to the shortcoming of Ocuphire to acquire ample further capital to proceed to advance its product candidates and its preclinical packages; (vi) legislative, regulatory, political and financial developments, (vii) modifications in market alternatives, (viii) the consequences of COVID-19 on medical packages and enterprise operations, (ix) the success and timing of commercialization of any of Ocuphire’s product candidates and (x) the upkeep of Ocuphire’s mental property rights. The foregoing evaluation of vital elements that might trigger precise occasions to vary from expectations shouldn’t be construed as exhaustive and must be learn along with statements which are included herein and elsewhere, together with the chance elements detailed in paperwork which were and could also be filed by Ocuphire now and again with the SEC. All forward-looking statements contained on this press launch converse solely as of the date on which they had been made. Ocuphire undertakes no obligation to replace such statements to mirror occasions that happen or circumstances that exist after the date on which they had been made.
Corey Davis, Ph.D.