Phase II: optimization of a nanoparticle-based topical PDE5I formulation for treatment of erectile dysfunction

Active Project Grant Awarded Last action

Award ID
R44DK129147
Recipient
Awarding agency
Obligated
$965,708

Award facts

Assistance listing
93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
Completion date 71% complete
Place of performance
South Carolina, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
This phase II proposal is a follow-up to the successful phase i studies in which we developed a novel topically applied sildenafil-nanoparticle (sildenafil-NP) formulation for improved treatment of erectile dysfunction (ED). Sildenafil, initially only used for treatment of ED, is now also used at low oral doses in penile rehabilitation, a strategy to maintain erectile tissue architecture after radical prostatectomy (RP). Despite its safety, sildenafil has side effects such as headache and facial flushing, and IT has issues with absorption affected by diet that can increase time-to-erection. These drawbacks could be mitigated with the topical sildenafil-NP formulation developed in the phase i study. This formulation aims to reduce systemic side effects, avoid absorption variability, bypass first-pass metabolism, and provide a more direct and continuous release of sildenafil. The phase i studies successfully showed that topical sildenafil-NP improved erectile function in aging rats. In specific aim 1A of this phase II proposal, we will test the efficacy of sildenafil-NP in improving erectile function in an animal model of type II diabetes; and in specific aim 1B, our goal is to demonstrate the efficacy of sildenafil- NP in preserving penile architecture and function after cavernous nerve injury, potentially aiding penile rehabilitation following RP. In specific aim 2 we will scale up the manufacturing capability in a GMP-compliant manner and generate a demonstration batch of sildenafil-NP for use in animal safety studies. In specific aim 3, we will conduct the animal safety studies required to support an IND application-specifically, we will assess the potential for sensitization in a guinea PIG dermal hypersensitivity study and also assess vaginal, oral, and rectal irritation by repeat-dose irritation studies. Finally, in specific aim 4, a pre-IND meeting will be held with the FDA to gain binding insights into remaining steps required for an IND application and initiation of a phase i clinical study. By the end of this phase II project: (1) the efficacy of topical sildenafil-NP in a diabetic RAT model of ED will be assessed and the ability of sildenafil-NP to prevent changes in molecular markers of erectile function and gross penile anatomy following RP-related injury will also be assessed; (2) a demonstration batch of sildenafil-NP will be produced; (3) four IND-enabling safety studies be successfully conducted; and (4) FDA feedback from a pre- IND meeting will be obtained. Soon after the conclusion of this grant, atticus will be well positioned to find a development/commercialization partner that will further the development of sildenafil-NP and advance the program into clinical trials.

Quick answers

Who received award R44DK129147?

R44DK129147 was awarded to Atticus Pharma Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 15, 2022.

How much is award R44DK129147 worth?

$965,708 has been obligated on R44DK129147.

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