About Aerpio Pharmaceuticals

Aerpio Pharmaceuticals, Inc. operates as a biopharmaceutical company. The company focuses on developing compounds that activate Tie2 in indications in which the activation of Tie2 may have therapeutic potential. Its product candidates include razuprotafib, a small molecule VE-PTP (vascular endothelial protein tyrosine phosphatase) inhibitor. In March 2019, the company announced topline results from its Phase 2b (TIME-2b) clinical trial of AKB-9778 for the treatment of non-proliferative diabetic retinopathy. Although the results did not meet the study’s primary endpoint, the TIME-2b study further supported the reduction of intraocular pressure (IOP) seen with subcutaneous razuprotafib in the previous TIME-2 study. Based on these findings, the company developed a topical ocular formulation of razuprotafib, and observed in preclinical studies activation of Tie2 in Schlemm’s canal, IOP reduction via enhanced outflow facility and favorable tolerability. In June 2019, the company initiated a double-masked, multiple-ascending dose Phase 1b clinical trial for open angle glaucoma (OAG). The company enrolled four cohorts of 12 subjects each and subjects received increasing daily doses of a topical ocular formulation of razuprotafib or placebo for seven days. The primary endpoint of the trial was ocular safety and tolerability, with IOP lowering as the key pharmacodynamic endpoint. Based on the unmasked interim analysis of Phase 1b, limited to the first three cohorts, which showed the topical ocular administration of razuprotafib was well tolerated, and a time and dose dependent reduction in IOP that, in the highest once daily (QD) dose cohort peaked at 4 hours post-dose and was sustained through eight hours on day 7, returning to baseline levels at 24 hours post-dose, a cohort of 43 patients with OHT (ocular hypertension)/OAG (open angle glaucoma) (hypertensive eyes) was added to the ongoing study to assess safety and pilot efficacy in the target patient population. In January 2020, the company announced the results of the fifth cohort of subjects noting subjects in cohort five randomized to the active arm exhibited statistically significant decreases in IOP at all post razuprotafib administration time points on both days 1 and 7 compared with day -1 baseline values when they were being treated with prostaglandin alone. When the change is placebo-corrected, razuprotafib plus prostaglandin versus prostaglandin alone produced a statistically significant decrease in IOP on Day 7 at 0, 4 and 8 hours post dose as compared to placebo. These results suggested a persistent IOP-lowering activity from adding razuprotafib to standard-of-care prostaglandin therapy. Topical ocular administration of razuprotafib was well tolerated over seven days in cohort five. There were no reports of conjunctival hemorrhage or pain on instillation during the seven days of dosing and no systemic/non-ocular AEs were observed. In June 2020, the company initiated a Phase 2 clinical trial designed to evaluate the safety and efficacy of a topical formulation of razuprotafib in approximately 195 patients followed over a 28-day period. Patients enrolled in the trial were administered a baseline of latanoprost ophthalmic solution 0.005%, and then randomized in a 1:1:1 fashion to receive adjunctive therapy consisting of placebo, 40 mg/ml razuprotafib once-daily, or 40 mg/ml razuprotafib twice-daily. The primary endpoint of the study was mean diurnal IOP at 28 days in the razuprotafib treated groups compared to the latanoprost monotherapy group. In December 2020, the company reported that razuprotafib met the primary efficacy endpoint at Day 28 with the twice-daily (BID) dose group in the company’s double-blind, placebo-controlled Phase 2 trial in patients with elevated IOP associated with OAG or OHT. The change from baseline in diurnal mean IOP at Day 28 of study eyes treated with razuprotafib BID plus latanoprost showed a statistically significant improvement, or drop in IOP (two-sided p-value 0.0130 and LS mean difference of -0.92 mm Hg) compared to those treated with latanoprost monotherapy. The razuprotafib QD dose group did not show a statistically significant improvement at Day 28. Further analysis of the results demonstrated that razuprotafib had a larger IOP reduction after longer duration dosing (28 days versus 14 days) consistent with its potential mechanism of repairing Schlemm’s canal. Following the announcement regarding the topline results from the Phase 2 clinical trial of razuprotafib in patients with elevated IOP associated with OAG or OHT, the company initiated a process to explore a range of strategic alternatives focused on maximizing stockholder value from its clinical and preclinical assets. As part of this process, the company is exploring strategic options for partnering its programs, as well as the potential for an acquisition, company sale, merger, business combination, asset sale, in-license, out-license or other strategic transaction. Other assets in the company’s pipeline include the following: Acute Respiratory Distress Syndrome Based on results in preclinical studies and observations in patients in TIME-2 and TIME-2b trials, a vascular endothelial receptor, Tie2, may play a pivotal role in the defense against microvascular breach in ARDS. The company hypothesizes that razuprotafib may have therapeutic potential for the treatment of COVID-19 associated ARDS and initiated two Phase 2 trials during 2020. Quantum Leap Healthcare Collaboration I-SPY COVID Trial In May 2020, the company was selected by Quantum Leap Healthcare Collaborative to participate in the I-SPY COVID Trial (Investigation of Serial studies to Predict Your COVID Therapeutic Response with biomarker Integration and Adaptive Learning) to evaluate subcutaneous razuprotafib for the treatment of COVID-19 related ARDS in adult patients with critical COVID-19. The trial was initiated during the third quarter of 2020 but in January 2021, the Data Monitoring Committee recommended discontinuation of razuprotafib after 21 patients due to the complexity of monitoring patients in the setting of a surge in ICU patients. MTEC RESCUE COVID Trial In August 2020, the company announced the receipt of funding to evaluate subcutaneous razuprotafib in a new randomized, investigational trial for the prevention and treatment of ARDS in adult patients with moderate to severe COVID-19 (RESCUE trial). The RESCUE trial will evaluate subcutaneous razuprotafib for the prevention and treatment of ARDS in adult patients with moderate to severe COVID-19 as part of the MTEC-20-09-COVID-19 Treatment Military Infectious Disease Research Program (MIDRP). The RESCUE clinical trial was initiated during the third quarter of 2020 but the company decided to stop recruiting in February 2021 after the first 31 patients were enrolled based on challenges recruiting and monitoring patients in the current pandemic environment. There were no apparent safety signals associated with dosing COVID-19 patients in the RESCUE trial and the company plans to further analyze the data to assess trends in efficacy and biomarkers. The company expects to report top-line data in the second quarter of 2021. Diabetic Kidney Disease In two consecutive trials, TIME-2 and TIME-2b, subcutaneous AKB-9778 showed reduction in Urine Albumin-Creatinine Ratio (UACR), a measure of progression of diabetic kidney disease. In a post-hoc analysis of the earlier TIME-2 clinical trial, there was a 21% reduction (geometric mean) in UACR from baseline in the AKB-9778 treatment arms, but an overall increase in UACR in the placebo arm. The prospective UACR analyses from the completed TIME-2b trial largely replicated the results from the previous trial and reinforced the potential beneficial effects of Tie2 activation in diabetic kidney disease. ARP-1536 and Bispecific Antibody ARP-1536, the company’s humanized monoclonal antibody directed at the same target as subcutaneous razuprotafib, is in preclinical development. The company is evaluating development options for ARP-1536, including subcutaneous injection for the treatment of diabetic vascular complications, e.g., diabetic nephropathy and intravitreal injection as an adjunctive therapy for diabetic macular edema. The company is also developing a bispecific antibody that binds both vascular endothelial growth factor (VEGF) and vascular endothelial protein tyrosine phosphatase (VE-PTP), which is designed to inhibit VEGF activation and activate Tie2. This bispecific antibody has the potential to be an improved treatment for wet aged-related macular degeneration and diabetic macular edema via intravitreal injection. Gossamer License Agreement In 2018, the company licensed GB004, a selective stabilizer of hypoxia-inducible factor-1 alpha (HIF-1 alpha) to Gossamer Bio, Inc. (Gossamer). GB004 is being developed for the treatment of inflammatory bowel disease (IBD). HIF-1 alpha is involved in mucosal wound healing and the reduction of inflammation in the gastrointestinal tract. After completing a 28-day Phase 1b study in ulcerative colitis patients during 2020, Gossamer initiated a 12-week Phase 2 study of GB004 in patients with mild-to-moderate ulcerative colitis during the second half of 2020 and expects to report top-line results from this study in the first half of 2022. Gossamer is responsible for all remaining development and commercial activities for GB004. Strategy The company’s strategies are to explore strategic collaborations with leading organizations for the development and commercialization of promising product candidates in its pipeline; investigate the sale, licensing or partnering of razuprotafib; and explore strategic options for further development of ARP-1536 and the Bispecific antibody. Intellectual Property As of December 31, 2020, the company owned at least 40 U.S. patents, at least 32 pending U.S. provisional or non-provisional patent applications, at least 286 foreign patents and at least 94 pending foreign applications, with claims directed toward various aspects of its product candidates and research programs, not counting patents and patent applications that have been licensed to a third party. Specifically, the claims of these patents and patent applications include compositions of matter, methods of use, drug product formulations, and methods of manufacture. Such patents and patent applications, if issued, are expected to expire on various dates from 2027 to 2041, without taking into account any possible patent term adjustments or extensions. Within the foregoing patent portfolio, as of December 31, 2020, the company owned at least 10 U.S. patents, at least 7 pending U.S. provisional or non-provisional patent applications, at least 52 foreign patents and at least 32 pending foreign applications that are directed toward ARP-1536 and formulations or uses thereof. As of December 31, 2020, within the foregoing patent portfolio, the company owned at least 30 U.S. patents, at least 25 pending U.S. provisional or non-provisional patent applications, at least 234 foreign patents and at least 62 pending foreign applications that are directed toward razuprotafib and formulations, medicinal chemistry variants or uses thereof. Such patents claiming compositions of matter directed toward ARP-1536 are set to expire in 2027, without taking into account any possible patent term adjustments or extensions. Such patents claiming compositions of matter directed toward razuprotafib are set to expire in 2027, without taking into account any possible patent term adjustments or extensions. Sales and Marketing The company holds worldwide commercialization rights to all of its product candidates. Government Regulation The company is subject to the U.S. Foreign Corrupt Practices Act.