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Development of microparticle-based topical treatments for treating erectile dysfunction in patients refractory to oral PDE5 inhibitors

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44DK121587-02
Agency Tracking Number: R44DK121587
Amount: $1,705,226.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 400
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-07-19
Award End Date (Contract End Date): 2023-06-30
Small Business Information
Greenville, SC 29601-4824
United States
DUNS: 080999429
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (908) 420-4814
Business Contact
Phone: (858) 775-6710
Research Institution

Following radical prostatectomy (RP), virtually all men experience erectile dysfunction (ED),
primarily due to damage to the cavernous nerve (CN). Yet, first-line treatments for ED, orally
administered phosphodiesterase 5 inhibitors (PDE5i), fail to elicit an erectile response for a
majority of patients suffering from ED as a result of RP (ED-RP). Alternative treatments are highly
invasive and/or have poor efficacy and are typically not even attempted. For a man who
experiences ED following RP, the trauma of back-to-back diagnoses (cancer and ED) has a
profound impact on quality-of-life, relationships, and well-being. There is, therefore, an urgent
need to find a novel approach to the treatment of ED in this patient group.
A primary factor in the development of ED-RP is that damage to the CN during RP impairs
neuronal signals that release sufficient NO from CN endings to initiate an erection. Thus,
formulations that increase local levels of NO may elicit an erectile response in the absence of
neuronal signals and may also enable cooperativity with PDE5i to enhance the erectile response.
This hypothesis was proven in Phase I where it was demonstrated that a novel transdermal
microparticle delivery system for NO (NO-MP) was able to elicit an erectile response when
administered alone or in combination with 1/10 the human equivalent dose of the leading PDE5i,
sildenafil. When NO-MP and sildenafil were used in combination, an improvement in the time for
onset of the first erectile response was observed, and the number of erections was greater than
treatment with NO-MP alone.
In Specific Aim 1 of Phase II, we will determine if the cooperativity in eliciting an erectile response
seen between NO-MP and sildenafil exists with other members of the FDA-approved PDE5i class.
This will confirm that the observation in Phase I is class-specific and will expand/define the
portfolio of potential commercial partners. In Specific Aim 2 we will initiate a GMP start-up program
at Zylö Therapeutics and confirm that a demonstration batch is as effective in eliciting an erectile
response as the small batch prep used in Specific Aim 1. Specific Aim 3 will establish the
maximum tolerated dose (MTD) in dose-range-finding studies conducted in rats and minipigs in
order to inform the design of later IND-enabling toxicology studies. In addition, a dermal sensitivity
study in guinea pigs and a dermal irritation study in rabbits will be conducted as part of the suite
of safety studies required by the FDA for topical products. Finally, in Specific Aim 4, a pre-IND
meeting will be held with the FDA to finalize remaining studies required for an IND application and
initiation of a Phase I clinical study.
At the conclusion of these phase II studies, we expect to have: (i) confirmed that NO-MP is
cooperative across the PDE5i class; (ii) generated a demonstration batch of NO-MP with
confirmed efficacy; (iii) conducted dermal toxicity studies to provide sensitivity and irritation data
and to establish the MTD; and (iv) consulted with the FDA regarding future development work
during a pre-IND meeting. Overall, we will be ready to initiate further toxicity studies in preparation
for an IND filing and a Phase I clinical trial.

* Information listed above is at the time of submission. *

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