Aerpio Pharmaceuticals, Inc. (Nasdaq: ARPO), a biopharmaceutical
company focused on developing compounds that activate Tie2 to treat
ocular diseases and diabetic complications, today announced new
results from the fifth cohort of subjects from a Phase 1b trial of
a topical ocular formulation of AKB-9778 providing evidence of
tolerability and IOP reduction from patients in that cohort with
ocular hypertension (OHT) or primary open angle glaucoma
(POAG).
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The Phase 1b trial is a randomized, double-masked study designed
to assess increasing concentrations of AKB-9778 dosed topically as
eye drops. The primary outcome of the study is ocular safety and
tolerability with change in intraocular pressure (IOP) at Day 7 as
a pharmacodynamic outcome. Conjunctival hyperemia and IOP were
assessed at 0 (pre-dose), 2, 4, and 8 hours post-dose on Day -1
(baseline), Day 1 (first day of AKB-9778 dosing) and Day 7 (last
day of AKB-9778 dosing). Results from the first 3 cohorts, each
comprising 12 subjects with normotensive eyes (non-glaucoma
subjects), were reported on October 10, 2019. Subsequently, results
from cohort 4, also containing 12 subjects with normotensive eyes,
were observed to be consistent with those from cohorts 1 through
3.
Based on favorable tolerability and pharmacodynamic findings in
these ocular normotensive subjects, Aerpio elected to recruit a
fifth cohort of subjects with OHT/POAG on standard of care
prostaglandin therapy to assess the safety, tolerability and pilot
efficacy of once-daily AKB-9778 (40 mg/ml) as an adjunctive
therapy. In the fifth cohort 43 patients were recruited with
OHT/POAG and baseline IOP measurements between 17 and 27 mmHg while
treated with once-daily prostaglandin therapy. Patients were
randomized 3:1 to receive either AKB-9778 (32 subjects) or placebo
(11 subjects), administered in the morning for 7 days, while
continuing their evening prostaglandin therapy. Conjunctival
hyperemia and IOP were assessed in the same manner as described for
cohorts 1-4 (see above).
Results from cohort 5 are as follows:
- Subjects in cohort 5 randomized to the active arm exhibited
statistically significant decreases in IOP at all post-AKB-9778
administration time points on both Days 1 and 7 compared with Day
-1 baseline values when they were being treated with prostaglandin
alone (see Figure 1; Diurnal = mean IOP of 2, 4 and 8 hour time
points; ** p < 0.05, *** p < 0.001).
- When the change is placebo-corrected, AKB-9778 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 (placebo-adjusted data at 0 hrs. -2.26 mmHg,
p = 0.007; 2 hrs. -1.24, p = 0.138; 4 hrs. -1.47 mmHg; p = 0.048; 8
hrs. -1.80 mmHg; p = 0.041). We believe these results suggest a
persistent IOP-lowering activity from adding AKB-9778 to
standard-of-care prostaglandin therapy.
Topical ocular administration of AKB-9778 was well tolerated
over seven days in cohort 5. In the active arm treated with
AKB-9778 plus prostaglandin, 18.8% of subjects experienced
hyperemia compared with 9.1% of subjects in the prostaglandin-alone
arm. In all cases, this hyperemia was minimal-to-mild in severity,
transient in duration and generally considered non-adverse. There
were no reports of conjunctival hemorrhage or pain on instillation
during the seven days of dosing.
“These early data suggest potential for a best in class profile
for AKB-9778 to lower IOP when used in combination with
prostaglandins,” said Brian Levy D.O., M.Sc., CEO of at Ocunexus
Therapeutics and former CMO of Aerie Pharmaceuticals. “Although
this is a small study, we observed IOP reductions in the fifth
cohort of this trial that are comparable to or better than those
produced by common commercial adjunctive therapies used in
conjunction with prostaglandins. Moreover, AKB-9778 was
well-tolerated through seven days of dosing with minimal hyperemia,
no conjunctival hemorrhage and no discomfort on instillation. I
look forward to the potential confirmation of these results in a
larger and longer duration study.”
Pravin U. Dugel M.D., Partner, Retinal Consultants of Arizona,
Clinical Professor, Roski Eye Institute, USC Keck School of
Medicine, and Member of Aerpio’s Board of Directors 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.”
Based on these results, Aerpio plans to further advance its
glaucoma program through strategic alternatives such as a
partnership or collaboration.
About AKB-9778
AKB-9778 binds to and inhibits vascular endothelial protein
tyrosine phosphatase (VE-PTP), an important negative regulator of
Tie2. Decreased Tie2 activity contributes to vascular instability
in many diseases including diabetes. AKB-9778 activates the Tie2
receptor irrespective of extracellular levels of its binding
ligands, angiopoietin-1 (agonist) or angiopoietin-2 (antagonist)
and may be the most efficient pharmacologic approach to maintain
normal Tie2 activation.
About Aerpio Pharmaceuticals
Aerpio Pharmaceuticals, Inc. is a biopharmaceutical company
focused on advancing first-in-class compounds that activate Tie2 to
treat ocular diseases and complications of diabetes. Tie2 is an
important regulator of vascular stability, and its down-regulation,
through activation of two inhibitors VE-PTP and Ang-2, is found in
patients with diabetes and other conditions. The Company’s lead
compound, AKB-9778, a first-in-class small molecule inhibitor of
VE-PTP, is being investigated in an ongoing Phase 1b clinical trial
as a topical drop formulation for its therapeutic potential in
open-angle glaucoma. In the recently completed Phase 2b study
(TIME-2b) AKB-9778 demonstrated the ability to lower proteinuria
(as measured by decreasing urinary albumin creatine ratio, UACR) by
about 20% replicating a finding in the previous Phase 2 study. The
decrease in proteinuria suggests that AKB-9778 and our other Tie2
activating drug, ARP-1536, may have the potential to improve kidney
function in diabetics potentially delaying progression to kidney
dialysis. The Company’s second asset, ARP-1536 is a humanized
monoclonal antibody observed to activate Tie2 receptors in a
dose-dependent manner in preclinical models. Aerpio believes
ARP-1536 holds potential as a monthly or biweekly systemic therapy
to treat diabetic complications, including diabetic nephropathy.
The Company’s third asset is a bispecific antibody that binds both
VEGF and VE-PTP which inhibits VEGF activation and activates Tie2.
This bispecific antibody has the potential to be an improved
product for treating wet AMD and diabetic macular edema via
intravitreal injection. Finally, the Company has exclusively
out-licensed its fourth asset AKB-4924 (now called GB004), a
first-in-class small molecule inhibitor of hypoxia-inducible
factor-1 (HIF). GB004 is being developed by AKB-4924’s exclusive
licensor, Gossamer Bio, Inc. (Nasdaq: GOSS), in return for an
upfront payment of $20 million, future potential development,
regulatory, and sales milestones of up to $400 million, and
royalties on worldwide net sales. For more information, please
visit www.aerpio.com.
Forward Looking Statements
This press release contains forward-looking statements.
Statements in this press release that are not purely historical are
forward-looking statements. Such forward-looking statements
include, among other things, the Company’s product candidates,
including AKB-9778, and the clinical development and therapeutic
potential thereof, its plans to further the development of its
glaucoma program, and the intended benefits from its collaboration
with Gossamer Bio, Inc. for GB004. Actual results could differ from
those projected in any forward-looking statements due to several
risk factors. Such factors include, among others, potential
disruptions in our business as a result of our exploration, review
and pursuit of strategic alternatives or the public announcement
thereof and any decision or transaction resulting from such review;
the ability to continue to develop AKB-9778 or other product
candidates; the inherent uncertainties associated with the drug
development process, including uncertainties in regulatory
interactions, commencing clinical trials and enrollment of patients
in clinical trials; and competition in the industry in which the
Company operates and overall market conditions; and the additional
factors set forth in our Annual Report on Form 10-K for the year
ended December 31, 2018, as updated by our subsequent filings with
the SEC. These forward-looking statements are made as of the date
of this press release, and the Company assumes no obligation to
update the forward-looking statements, or to update the reasons why
actual results could differ from those projected in the
forward-looking statements, except as required by law. Investors
should consult all the information set forth herein and should also
refer to the risk factor disclosure set forth in the reports and
other documents the Company files with the SEC available at
www.sec.gov.
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version on businesswire.com: https://www.businesswire.com/news/home/20200108005257/en/
Investor & Media:
Aerpio Pharmaceuticals, Inc. Gina Marek VP of Finance
gmarek@aerpio.com or Burns McClellan, on behalf of Aerpio
Pharmaceuticals, Inc. Media:
Robert Flamm, Ph.D. rflamm@burnsmc.com or Investors: John Grimaldi jgrimaldi@burnsmc.com
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