Sheryl Zwerski, MSN, CRN

November 5, 2014

Prevention Sciences Program

Present & Future

Overview

• Orientation to PSP

• Program Objectives

• Major Projects/Programs

– Contracts

– Programs

– Networks

• Future Scientific Directions

DAIDS/PSP

Office of the Director

Sheryl Zwerski, Acting DirectorFulvia Veronese, Assistant Director

Cherlynn Mathias, Program Grants CoordinatorA J Reece, Program Assistant

Millicent Moye, Program AssistantJohn Wroblewski, Program Specialist

Preclinical Microbicideand Prevention

Research BranchJim Turpin, ChiefJames CumminsLeslie MarshallAnabel LowryKristen PorterHans Spiegel

Mike Gilbreath

Clinical MicrobicideResearch BranchRoberta Black, ChiefJeanna Piper, Deputy

Lydia Soto-TorresGrace Chow

Lester FreemanNaana Cleland

Prevention Sciences Program

Clinical Prevention Research BranchDavid Burns, Chief

Vanessa Elharrar, DeputyWairimu Chege

Alain KoudaElizabeth Flanagan

Usha SharmaAnnie Waterman

November 10, 2014 *Contractor

Maternal, Adolescent, &Pediatric Research

BranchDevasena Gnanashanmugam

ChiefBetsy Smith

Patrick Jean-PhilipeJudi Miller

Ellen O’GaraRenee Browning

PSP Objectives

1.) Deliver prevention tools that can reduce HIV incidence in populations at risk by:

– Creating and sustaining a pipeline for non-vaccine HIV prevention products using rational development algorithms with clear go/no go criteria focused on:

• Sustained delivery methods

• Combination products (combination ARVs and MPTs)

DAIDS/PSP

PSP Objectives

• Supporting clinical product development activities that include appropriate safety and efficacy testing as well as integrated PK/PD assessments and advance HIV prevention candidates to licensure, specifically:

–Topical microbicides (vaginal and rectal)

–Systemic pre-exposure prophylaxis (PrEP)

–Other novel prevention products (including biological, drugs and devices)

DAIDS/PSP

PSP Objectives

• Supporting efforts to improve treatment as prevention by optimizing the testing, linkage to care and treatment cascade.

2.) Support efforts to optimize HIV treatment for pregnant women, infants, children, and adolescents.

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PSP Objectives

3.) Contribute significantly to the advancement of DAIDS cure agenda in infants and children.

4.) Supports efforts to transform the diagnosis, prevention, and treatment of TB and other co-infections of importance in the maternal/child population.

DAIDS/PSP

PSP Objectives

5.) Partner with our NIMH and NIDA colleagues in both the clinical and the preclinical arenas to incorporate behavioral research:

• ADHERENCE

• Accurate assessment of likelihood of intervention uptake

• Assessment of risk for ppts and providers

• Effective coping with stigma

• Substance use’s effects on all of the above

– Development of strategies to effectively engage this population

DAIDS/PSP

Contract Resources for Microbicides and Prevention

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3 Current Work Scopes•Gap-Filling•Development Planning•Best Practice Working Groups (BPWG)

Accomplishments:•Collaborating with Merck with IND enabling preclinical toxicity studies for combination vaginal ring•Supported MTN 013 with extractable and leachable studies•Optimizing biophysical properties of single and combo ARV ring for IPM•Performed multiple rabbit vaginal and rectal irritation studies to enable Phase I studies

Future:•RFP in development

Preclinical Programs

Mucosal Environment and HIV Prevention (MEHP)

Objective: Enhancement of HIV microbicide, PrEP and MPT prevention strategy efficacy and safety by understanding their interaction with the male and female genital and GI mucosa and optimizing that interaction to better promote inhibition of HIV transmission and acquisition

Accomplishments:

• Robust responses with varied topics of exploration

Future:

• Current round of funding should assure robust investigations on the topic and consideration of future iterations is underway

DAIDS/PSP

Preclinical Programs

Preclinical Innovation Program (PIP)

Objective: Preclinical discovery and testing of single and

combination drug strategies and promotion of the

integration of new safety, efficacy and adherence

technologies into the prevention pipeline.

Accomplishments:

• Robust response which included truly innovative delivery

systems and validation of needed safety models

Future:

• Under consideration given fiscal constraints and

program needs

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Integrated Preclinical/Clinical Program (IPCP)

Objective: Stimulate a strong, diverse base in preclinical discovery and development of new topical microbicides and biomedical prevention for vaginal, rectal, penile and oral/injectable use and support translation from preclinical to pre-Phase 1 clinical studies

Accomplishments

• CROI 2014 presentation of first in human film study

• First testing of rectal specific TFV gel

• Begun pre-phase I study of TDF IVR with novel ring platform

Future

• Future program needs being considered

Preclinical Programs

DAIDS/PSP

Preclinical Programs

Sustained Release of Antivirals for Treatment and Prevention (Collaboration between PSP and TRP)

Objective: Build a pipeline of long acting release formulations for non-vaccine biomedical prevention (microbicide, PrEP) and therapeutic candidates with a goal of a minimum of once a month dosing

Accomplishments:

• PAR and FOA released earlier in 2014

Future:

• Consideration underway for best way to stimulate the area for prevention

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Clinical Programs Methods for Prevention Packages Program (MP3)

Objective: Increase collaborations between behavioral and biomedical clinical scientists, modelers, and clinical trialists to facilitate the design and testing of combination HIV prevention interventions (prevention packages)

Accomplishments:

• First 6 projects are completing

• Packages must be population and region/locality specific

• Cost effectiveness of package is epidemic context dependent

Future:

• Received robust response to recent PAs

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Clinical Programs

Increased Knowledge and Innovative Strategies to Reduce HIV Incidence (iKnow)

Objective: Promote innovative research to improve our ability to identify populations that are both at high risk of HIV-1 infection and have a high proportion of persons that are unaware of their HIV status, and to successfully link them to HIV testing, effective prevention interventions, and, if HIV-positive, care and treatment

Accomplishments:

• PAR released and robust response received

Future:

• Need is well documented, future funding uncertain

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IMPAACT Clinical

Trial Network

DAIDS/PSP

IMPAACT Mission

• Areas of focus for pregnant women and children

– HIV Treatment

– HIV Prevention

– HIV Cure

– HIV Co-morbidities & Complications

– TB diagnosis, treatment, and prevention

HIV Prevention

Trials Network

(HPTN)

DAIDS/PSP

HPTN Mission

• Discover and develop new and innovative research strategies to reduce the acquisition and transmission of HIV.

– Develops systemic PrEP, including long-acting products

– Does not develop vaccines or microbicides, but integrates once efficacy data available

Microbicide Trials

Network

(MTN)

DAIDS/PSP

MTN Mission

• Bring together investigators, community, and industry partners to work on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV.

• Collect the kind of data regulatory agencies require for determining whether to approve a product for widespread use.

• Behavioral and social science is embedded within each study to gain understanding of the needs and desires of different high-risk groups.

• Include populations considered among those at highest risk, including women in Sub-Saharan Africa, adolescents, pregnant and breastfeeding women, transgender women and men who have sex with men (MSM).

The Future for Prevention

Sciences Program

• Build a pipeline of sustained release products for prevention

– Topical micobicides

– PrEP

• Increase contextual awareness

– Micro & Macro environments

• Mucosal level

• Population level

DAIDS/PSP

The Future for Prevention

Sciences Program

• Integrate behavior into all phases of study, including

preclinical

– Understand what women (and men) want

• Lessons learned must remain at the forefront of all

future work

• Explore innovative trial methodologies/evidence required for moving prevention products and packages forward

DAIDS/PSP

The Future for Prevention

Sciences Program

• Sharpen focus on the Testing & Treatment Cascade

– Improve testing strategies for most at risk

– Improve linkage and engagement in care

• Support testing of integrated prevention strategy packages that are appropriate, acceptable and cost effective for target populations

• Increase efforts to deliver strategies that can be scaled up to reduce incidence in adolescents– Young MSM globally

– Females in SSA

DAIDS/PSP

• Focus on achieving appropriate safety and PK/PD of new ARVs for pregnant women, children and adolescents – Optimize first line treatment from infancy through adolescence

• Partner with other DAIDS programs, ICs, and agencies to explore all reasonable efforts to explore infant cure

• Partner with other DAIDS programs, NIAID divisions, ICs and outside donors to improve TB diagnosis, prevention, and treatment for pregnant women and children

DAIDS/PSP

The Future for Prevention Sciences Program

Discovery Preclinical

Virology Clinical Studies

I II IIIPreclinical

Studies

(Critical Path)

Pre-

Phase I

Studies

Comprehensive Resources for Topical Microbicides

and Biomedical Prevention (CRMP)

Microbicide Trials Network

Prevention Trials Network

Mucosal Environment

and HIV Prevention

(MEHP II)

Prevention Innovation

Program (PIP)

Sustained Release Program for non-Vaccine Biomedical Prevention and Therapeutics

(SRP-nBPT)

Integrated Preclinical Clinical Program

for Microbicides and Biomedical

Prevention (IPCP-MBP)

Prevention Sciences Program Pipeline

IKNOW (PA)

MP3-III (PA)

IMPAACT NetworkIMPAACT Network

Thank You for

Listening!

Questions?DAIDS/PSP