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IND-enabling preclinical development of a sustained-release Pritelivir intravaginal ring for the treatment and prophylaxis of Genital Herpes in women

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AI136201-02A1
Agency Tracking Number: R44AI136201
Amount: $1,860,561.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA18-574
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-04-04
Award End Date (Contract End Date): 2021-03-31
Small Business Information
2285 FOODHILL BLVD
Pasadena, CA 91107-3658
United States
DUNS: 148679884
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 THOMAS SMITH
 (626) 372-0386
 tsmith@auritec.net
Business Contact
 THOMAS SMITH
Phone: (626) 376-4070
Email: tsmith@auritecpharma.com
Research Institution
N/A
Abstract

SUMMARY (changes are underlined)
The broad, long-term goal of this project is to develop a pritelivir intravaginal ring (IVR) for the treatment and
pre-exposure prophylaxis of genital herpes, a common problem that affects more than 50 million Americans.
Recurrences are common and may be painful. Infection is life-long. Pritelivir is a promising α-helicase inhibitor
that proved superior to existing therapies in Phase 2 clinical trials, but whose clinical development as a
systemic therapy has been arrested because of toxicity. Local therapy is therefore of special interest.
We have developed a platform technology for the sustained release of antivirals. This technology led to the
development of a ganciclovir intraocular implant - Vitrasert®, for the treatment of AIDS-related cytomegalovirus
retinitis. The Vitrasert® is the only sustained release antiviral drug delivery product to be ever approved by the
FDA. We have adapted this platform to IVRs and have successfully delivered other antiviral agents at
therapeutic levels in preclinical and clinical trials. We propose to utilize this platform to develop sustained
release IVR formulation for pritelivir. We achieved the specific aims of Phase I of this proposal which were to
formulate sustained release intravaginal rings delivering pritelivir, to test the in vitro release characteristics of
these formulations, and to test the in vivo safety and pharmacokinetics (PK) of the formulations in the FDA-
approved sheep model. The successful completion of Phase I has enabled us to identify an IVR dose for the
further development of a drug product that is safe, demonstrates sustained release for 28 days at satisfactory
cervicovaginal fluid and tissue drug levels that will provide high potential efficacy.
We, therefore, propose in Phase II to accomplish the FDA-mandated scientific and regulatory activities
required to enable an Investigational New Drug (IND) approval. We propose to develop GMP manufacturing
capacity for clinical lots of the lead formulation; to conduct a 3-month GLP, IND-enabling safety study in a
sheep model to examine local and systemic toxicity of extended IVR use; to perform manufacturing process
development, including product testing assays and early validation; to transfer manufacturing and analytical
methods to a contract manufacturing organization; to perform IND-enabling chemistry, manufacturing and
controls (CMC) activities for an IND submission; to complete and submit all clinical documents; and to
coordinate all activities to submit an IND application to the FDA. The milestone for the successful completion of
the proposed Phase II work is the approval of an IND to perform a first-in-human exploratory clinical trial. In
Phase IIB of this grant, we will test the lead formulation for safety, PK and efficacy in HSV+ve volunteers. The
team of investigators is expert in drug development, synthetic chemistry, pharmacokinetics, and clinical
infectious disease. We have experience in collaborating with large pharmaceutical companies to enable New
Drug Approvals (NDAs) of novel drug delivery systems. This project could lead rapidly to the development of
an improved treatment and prophylaxis for genital herpes.NARRATIVE
The broad, long-term goal of this project is to develop a pritelivir intravaginal ring for the treatment and pre-
exposure prophylaxis of genital herpes, a common problem that affects more than 50 million Americans. On
average, recurrences occur 4 times a year, and infection is life-long. Pritelivir is a promising α-helicase inhibitor
that proved superior to existing therapies in Phase 2 clinical testing, but whose clinical development as a
systemic therapy has been arrested because of toxicity. Local therapy is therefore, of special interest. We have
developed a ring technology platform and have successfully delivered other antiviral agents at therapeutic
levels in animal models and in clinical trials. Based on this platform, in a Phase I SBIR grant, we formulated
pritelivir rings, and demonstrated safety and clinically relevant pharmacokinetics in an FDA-approved sheep
model. We, therefore, propose a Phase II SBIR proposal to perform FDA-mandated Chemistry, Manufacturing
and Controls (CMC), pre-clinical in vivo studies and protocol development in order to enable an Investigational
New Drug (IND) approval. Successful completion of this work will lead to first-in-human clinical trial in a follow-
on Phase IIB SBIR proposal.

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

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