razuprotafib topical (AKB-9778 topical) / EyePoint Pharma - LARVOL DELTA

Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension. (PubMed, Transl Vis Sci Technol) - "Topical ocular razuprotafib as an adjunct to latanoprost therapy was well tolerated and significantly reduced IOP in patients with OAG/OHT. These data support the IOP lowering efficacy of targeting Tie2 activation in Schlemm's canal in the relevant patient population."

Clinical • Journal • Glaucoma • Ophthalmology

Study to Assess the Efficacy, Safety and Tolerability of AKB-9778 Ophthalmic Solution as and Adjunct to Latanoprost in Patients With Ocular Hypertension or Open Angle Glaucoma (clinicaltrials.gov) - P2; N=194; Completed; Sponsor: Aerpio Therapeutics; Recruiting ➔ Completed

Clinical • Trial completion • Glaucoma • Hypertension • Ophthalmology

A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure. (PubMed, Invest Ophthalmol Vis Sci) - "This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma."

Journal • Diabetic Retinopathy • Glaucoma • Hypertension • Ocular Infections • Ophthalmology • Retinal Disorders • EGF

Macular and Peripapillary OCTA Metrics Predict Progression in Diabetic Retinopathy: A Sub-analysis of TIME-2b Study Data. (PubMed, Am J Ophthalmol) - "FAZ area and temporal peripapillary VD are predictors of DR progression. OCTA metrics may improve progression risk assessment in DR when compared to established risk factors alone."

Journal • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

The VE-PTP Inhibitor AKB-9778 Improves Antitumor Activity and Diminishes the Toxicity of Interleukin 2 (IL-2) Administration. (PubMed, J Immunother) - "The findings suggest that AKB-9778 may function through reducing serum angiopoietin 2 level and regulating EC viability. These findings provide insights into the targeting VE-PTP to improve tolerance and efficacy of IL-2 therapy and highlight the clinical potential of AKB-9778 for treating patients with VLS and cancer."

Journal • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Study to Assess the Efficacy, Safety and Tolerability of AKB-9778 Ophthalmic Solution as and Adjunct to Latanoprost in Patients With Ocular Hypotension or Open Angle Glaucoma (clinicaltrials.gov) - P2; N=195; Recruiting; Sponsor: Aerpio Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Glaucoma • Hypertension • Hypotension • Ophthalmology

Study to Assess the Efficacy, Safety and Tolerability of AKB-9778 Ophthalmic Solution as and Adjunct to Latanoprost in Patients With Ocular Hypotension or Open Angle Glaucoma (clinicaltrials.gov) - P2; N=195; Not yet recruiting; Sponsor: Aerpio Therapeutics

Clinical • New P2 trial • Glaucoma • Hypertension • Hypotension • Ophthalmology

Aerpio Therapeutics announces presentation of positive results of AKB-9778 in patients with diabetic retinopathy from TIME-2 phase 2a study (Businesswire) - P2a, N=144; TIME-2 (NCT02050828); Sponsor: Aerpio; "Aerpio Therapeutics...announced promising results in diabetic retinopathy from the company’s phase 2a study ('TIME-2') of its lead candidate, AKB-9778...Rates of 2-step improvement were 10.0%, and 11.4% in the AKB-9778 monotherapy and AKB-9778+Lucentis combination therapy arms, respectively, compared to 8.8% of patients receiving Lucentis® alone."

P2a data • Diabetic Macular Edema • Ophthalmology

Aerpio Therapeutics reports peer-reviewed publication of positive clinical results from the phase 2a study of lead candidate, AKB-9778, in diabetic macular edema (DME): The TIME-2 trial (Businesswire) - P2a, N=144; TIME2 (NCT02050828); Sponsor: Aerpio; "The combination of Aerpio’s AKB-9778, a Tie2 activator, and Lucentis® demonstrated significant benefit versus Lucentis® monotherapy in reduction of macular edema following 3 months of treatment. Systemically administered AKB-9778 monotherapy also demonstrated the ability to improve underlying diabetic retinopathy by 2 or more steps in both study and fellow eyes without the need for intraocular injections. In addition, AKB-9778 showed an excellent safety profile."

P2a data • Diabetic Macular Edema • Ophthalmology

AKB-9778: IND filing for open angle glaucoma in Q4 2018 (Aerpio Therapeutics) - Corporate Presentation: Top-line data from P1b trial for open angle glaucoma in Q3 2019

IND • P1 data • Glaucoma • Ophthalmology

Aerpio Pharmaceuticals completes patient enrollment in TIME-2b study, a phase 2b clinical trial of lead candidate AKB-9778 in patients with diabetic retinopathy (Aerpio Therapeutics Press Release) - "Aerpio Pharmaceuticals...announced today the completion of patient enrollment in the company’s TIME-2b study, a Phase 2b clinical trial designed to assess the efficacy and safety of Aerpio’s lead candidate AKB-9778 for patients with moderate to severe non-proliferative diabetic retinopathy."

Enrollment closed • Diabetic Macular Edema • Ophthalmology

AKB-9778, anti-VEGF combination therapy yields favorable results in TIME-2 trial (Healio) - P2, N=141; NCT02050828; Sponsor: Aerpio Therapeutics; "At 3 months, 11.4% of patients in the combination group had greater than a two-step improvement on the diabetic retinopathy severity scale compared with 10% in the ranibizumab group and 8.8% in the AKB-9778 group...phase 3 study still needs to be done..."

P2 data • Ophthalmology

AKB-9778: Initiation of P1b study for open angle glaucoma in Q1 2019 (Aerpio Therapeutics) - Corporate Presentation: Initiation of P2a study for open angle glaucoma in Q4 2019

New P1 trial • New P2a trial • Glaucoma • Ophthalmology

AKB-9778: Patent expiry related to composition-of-matter in US/ex-US in 2027 (Aerpio Therapeutics) - Annual Report 2019

Patent

Predictive Value of ERG, OCT-A, and UWF-FA in Patients with Diabetic Retinopathy (ARVO 2020) - "Purpose To assess the value of electroretinography (ERG), OCT-angiography (OCT-A), and ultra-wide field fluorescein angiography (UWF-FA) parameters to predict progression of diabetic retinopathy in eyes with moderate to severe non-proliferative diabetic retinopathy (NPDR).Methods In the TIME-2b trial 167 patients with NPDR were randomized to receive 48 weeks of treatment with AKB-9778 (a Tie2 activator) 15 mg once or twice daily, or placebo...Pre-treatment ERG and OCT-A parameters were better predictors of progression to DME/PDR than DRSS or UWF-FA over 48-weeks of follow-up. The combination of functional and structural measures was better than either alone."

Clinical

Aerpio Pharmaceutical’s AKB-9778 produced IOP lowering with minimal hyperemia when combined with prostaglandin (Eyewire News) - P1, N=NA; "Pravin U. Dugel, MD...said, 'The opportunity to treat glaucoma via a novel mechanism-of-action that targets the Schlemm’s canal and the primary outflow channel may provide great benefit for patients beyond current therapies and definitely warrants further study. In addition to an impressive IOP-lowering activity on top of a prostaglandin, the encouraging tolerability profile observed from this cohort is also important for patient acceptance and compliance, as most current therapies have tolerability issues.'"

Media quote • P1 data

Aerpio reports third quarter 2019 financial results and provides business update (Businesswire) - "Research and development expenses for the three months ended September 30, 2019, decreased $1.5 million, or 34.6%, compared to the same period in 2018. This decrease was primarily the result of decreased expenses associated with the TIME-2b clinical trial of AKB-9778, offset by spending related to the Phase 1b clinical trial of topical drop formulation of AKB-9778, which commenced during the second quarter of 2019."

Commercial

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. (PubMed, Expert Opin Investig Drugs) - "Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study...AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert Opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities."

Journal • Review

Aerpio Pharmaceuticals announces interim results from its phase 1b clinical trial of topical ocular formulation of AKB-9778 for primary open angle glaucoma (Businesswire) - P1, N=NA; "Aerpio Pharmaceuticals...announced interim results from its Phase 1b clinical trial of a topical ocular formulation of AKB-9778 in development as a potential treatment for primary open angle glaucoma (POAG)....Compared to placebo, there was a dose dependent increase in minimal to mild conjunctival hyperemia with AKB-9778, which was transient and generally considered non-adverse. There was also a time and dose dependent reduction in IOP that, in the highest QD dose cohort peaked at 4 hours post-dose (-1.47 mmHg; p = 0.041)/-10.64%; p = 0.027) and was sustained through eight hours on day 7, returning to baseline levels at 24 hours post-dose....The Company expects to announce full results of the ongoing Phase 1b study in the first quarter of 2020."

P1 data

Aerpio reports second quarter 2019 financial results and provides business update (Businesswire) - "Research and development expenses for the three months ended June 30, 2019, decreased $2.0 million, or 46.5%, compared to the same period in 2018. This decrease was primarily the result of decreased expenses associated with the TIME-2b clinical trial of AKB-9778."

Commercial

The TIME-2b Study: A Study of AKB-9778, a Novel Tie 2 Activator, in Patients With Non-Proliferative Diabetic Retinopathy (NPDR) (clinicaltrials.gov) - P2; N=167; Completed; Sponsor: Aerpio Therapeutics; Active, not recruiting ➔ Completed; Trial completion date: Jun 2019 ➔ Feb 2019; Trial primary completion date: May 2019 ➔ Jan 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

Aerpio Pharmaceuticals presents data showing potential of AKB-9778, a VE-PTP inhibitor/Tie2 activator, to lower intra-ocular pressure in human subjects (Businesswire) - P2, N=144; TIME-2 (NCT02050828), P2, N=165; TIME-2b (NCT03197870); Sponsor; Aerpio Therapeutics; "Aerpio Pharmaceuticals...presented data showing the potential of AKB-9778, a VE-PTP inhibitor and Tie2 activator, to lower intra-ocular pressure (IOP) in human subjects. The data were presented as part of Special Session, entitled 'The Role of the Tie2 Pathway in Ocular Disease,' at The Association for Research in Vision and Ophthalmology (ARVO) 2019 Annual Meeting on May 1 in Vancouver, British Columbia...In both studies, measurements of IOP were prospectively included as safety outcomes in the study protocols."

P2 data

By targeting Tie2/VE-PTP in Schlemm’s canal, AKB-9778 lowers intraocular pressure via increasing outflow facility in mice (ARVO 2019) - "Conclusions Tie2 and VE-PTP were co-expressed in endothelium of SC and collector channels, and VE-PTP inhibition significantly reduce IOP and enhanced outflow facility in normotensive mice. These findings support evaluation of Tie2 activation by AKB-9778 as the first SC-targeted approach for IOP reduction in patients with open angle glaucoma or ocular hypertension."

Preclinical

The Role of the Angiopoietin-Tie2 Pathway in Microvascular Complications of Diabetes Mellitus (ENDO 2019) - P2; "The TIME-2 study (NCT02050828) was performed to examine the efficacy of AKB-9778 for the treatment of diabetic retinopathy and nephropathy. TIME-2 was a multicenter randomized trial in which 144 diabetic patients with center-involved diabetic macular edema (DME) were randomized (1:1:1) to 3 months of treatment with 15 mg AKB-9778 administered subcutaneously (SC) BID plus monthly intravitreal treatment (IVT) with 0.3 mg ranibizumab (RBZ), 15 mg AKB-9778 plus sham IVT, or RBZ plus placebo SC injections BID. The TIME-2 study provides evidence that restoration of Tie2 activity by AKB-9778 has beneficial effects on retinal and kidney function in patients with diabetes mellitus. A one-year treatment trial is currently underway. AKB-9778 is a promising therapeutic for the prevention of end-organ damage in diabetic patients.*Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation."

AKB-9778: Patent expiry related to composition of matter in US/ex-US in 2027 (Aerpio Therapeutics) - Annual Report 2018

Patent