1. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar

2. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Thank You For Joining Us!  During the webinar please mute your line using *6 if you are not speaking and unmute using *7 if you have a question or comment.  During the updates and presentations you can also use the chat feature to ask questions or make comments.  If you experience any technical difficulties during the webinar, please contact ReadyTalk Support.

3. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar 18 November 2014  Live Webinar  Hosted by CAMI Health

4. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Webinar Objectives  Provide brief a summary of prioritized scientific agenda working group (SAWG) activities since April 2014;  Proposed Steering Committee and funding agency collaboration activities moving forward and discussion; and  Input on initiative funding.

5. Steering Committee & Supporting Agency Collaboration Committee Bi-Annual Status and Planning Webinar - 18 November 2014 Moderators: Joseph Romano Bethany Young Holt Update on Prioritized SAWG Activities

6. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 SAWG Update  MPT Product Prioritization Survey FY14 recommendations Next steps for FY15  Dosage-form TPPs  Commercialization/Social-Behavioral TPP elements framework  Discussion

7. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 MPT Product Prioritization Survey: Process  Round 1: Survey developed and sent to 12 SAWG members in February 2014.  Survey revised based on comments and feedback.  Round 2: Revised survey sent to 109 people identified by SAWG as key stakeholder informants.  Received 21 responses to survey.

8. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 MPT Product Prioritization Survey: Respondent Demographics Survey Respondents by Country (N=21) Survey Respondents by Professional Identity (N=21)

9. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Key Findings  In 2013, the IMPT’s Scientific Agenda Working Group (SAWG) prioritized prevention of HIV, unintended pregnancy and other STIs as the most relevant MPT indications.  Have there been any developments that justify changing the priority indications, drugs, or dosage-forms identified last year? Clear answer from responses is “NO” APIs: ARV and HC prioritized, STI lacking (gap) IVR = Injectable > on-demand Viral STI > other STIs HSV > HPV

10. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Key Findings – cont.  Other priorities Non-HC options for contraception Issues with surfactants, rProteins, polyAs Advantages with small molecules and approved drugs ARV options not used for treatment preferred  Is there adequate acceptability data for each dosage- form and product, and is there sufficient commercialization feasibility assessments for these products? “NO”  Strong acceptance of co-admin injectables as an MPT  Films and tablets were favored over gels  Inadequate data/knowledge on the use of HC and ARV in on-demand products.

11. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 MPT Product Prioritization Survey: Plan for Moving Forward  Is prioritization exercise as currently configured of value?  Could modifications be made to make this a more rigorous, robust exercise? Partnered with other market data? Diversification of respondent pool? Content/format of the survey? IRB approval? Size and statistical significance?  Frequency?

12. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Dosage-Form TPPS: Process  Round 1: TPPs were distributed to SAWG/SACC members in the Spring 2014  Round 2: TPPs were distributed to non-developers and responses were received and reviewed.  Dosage-form TPPs were then revised based on feedback.  Round 3: Revised TPPs were distributed to developers for comments and feedback.  In total, received input from 12 stakeholders, 3 developers and 9 non-developers

13. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Dosage-Form TPPs Dosage-formNumber of reviewers Intravaginal Rings8 Long Acting Injectables7 On-demand Products9

14. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Commercialization & Social- Behavioral TPP Elements: Process  Framework sent out to 30 respondents to-date.  Feedback is being received and compiled for further discussion and refining of key elements for inclusion into the MPT TPPs.  Development of this framework is an ongoing and iterative process. Purpose: Move beyond the technical feasibility and licensure issues to the acceptability and demand issues so that products can be killed if they do not meet critical socio-behavioral commercialization points.

15. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Outcomes & Next Steps 1) Where does this leave us in terms of challenges? 2) What are your recommendations for actionable next steps, including possible meeting topics?

16. Steering Committee & Supporting Agency Collaboration Committee Bi-Annual Status and Planning Webinar - 18 November 2014 Moderator : Anke Hemmerling HC in MPTs Technical Meeting: Outcomes & Recommendations

17. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Objectives of the HC MPT meeting  Unite experts in contraception and MPT development to discuss relevant contraceptive research to help guide MPT development and investment decisions.  Inform product developers and supporting agencies about expert recommendations for the use of hormonal contraception (HC) in MPT products.  Discuss appropriate strategies for including HC into MPT products between contraceptive experts and MPT developers.

18. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Barriers to Conception conception Exposure ovulation Cervical mucus Endometrial effects Others ?? The Layers-of-Cheese Model, courtesy of Kurt Barnhart

19. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Current efforts in MPT Development  CONRAD: phase 1 safety and PK for Tenofovir and LNG reservoir IVR (polyurethane)  IPM: phase 1 dapivirine matrix EVA IVR with LNG to start in 2015  Population Council: partial reservoir/matrix EVA IVR for MIV-150 + Zinc + Carrageenan + LNG.

20. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Summary of current knowledge and gaps in HC Research 1  Mechanism of Action Systemic effects: HC plasma levels high enough for Anovulation have highest contraceptive efficacy Topical effects: protection by endometrial thickness and cervical mucus as MoA independently of Anovulation unclear LNG to date the HC with most data Problems:  Low dose HC [LNG patch] with high level of ovulatory cycles and favorable mucus  Many ovulatory cycles with high BMI  Other APIs may impact LNG levels

21. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Summary of current knowledge and gaps in HC Research 2  Surrogate markers for effectiveness: Many old HC studies with pregnancy as main outcome measure To determine PK and PD and interaction with other APIs, new markers and meaningful thresholds for markers needed  HC concentrations (e.g. LNG) not tightly correlated with ovulation and other markers (progestin, SBGH, LH)  Cervical mucus and endometrial thickness generally correlated with ovulation, but antiquated measurement techniques  High acceptability only with methods that ensure regular bleeding patterns and cycle control  High HC levels problematic  combined HC with EE could be more effective with fewer side effects  Scarce data on IVR removal and expulsion during sex, sex during menses, bleeding patterns

22. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 HC-MPT Drug-Drug Interaction  Role of Cytochrome P450 Enzyme System for drug metabolism for Protease inhibitors (PIs) and Non- nucleoside reverse transcriptase inhibitors (NNRTIs)  NNRTIs: Data on efavirenz suggests that LNG levels lowered by 60% (Perry 2014) Data on efavirenz suggests that ENG levels lowered by 60% (Vieira 2014) Nevirapine seemingly without effect No data on dapivirine  NRTIs: Tenovofir not affected

23. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 HC  CYP (Induction) Potential Sequelae from Sub-Therapeutic Dose: Pregnancy (P) and BTB (E) HC  CYP (Inhibition) Potential Side Effects/Drug Toxicity Drug level

24. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Gaps for the MPT field  Urgent need for more PK/PD data and research on drug-drug interactions of ART (NNRTIs, PIs) and HC (LNG, ENG)  Research needed on MoAs other than anovulation, topical effects, impact of high BMI,  Look beyond IVRs to also consider on-demand and long-acting formulations for MPTs  Research needed on surrogate markers and thresholds for contraceptive and HIV effectiveness  Novel robust acceptability and commercial feasibility measures are needed for key MPT user groups

25. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Issues for Discussion  Risks of specific ARVs and/or HC strategies in MPTs related to increased HIV acquisition  HC beyond LNG  Unknowns about drug-drug interactions  Appropriate dosing of HC and ART in combination  Surrogates of effectiveness for contraception or HIV beyond pregnancy and HIV+ infection  Justification of MPT - better than single indication

26. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Outcomes & Next Steps Regarding the outcomes of the HC in MPTs Technical Meeting in September 2014: 1) Where does this leave us in terms of challenges? 2) What are your recommendations for actionable next steps, including possible meeting topics?  Comments from the Contraceptive Perspective  Comments from the HIV Perspective

27. Steering Committee & Supporting Agency Collaboration Committee Bi-Annual Status and Planning Webinar - 18 November 2014 FY15 IMPT Convenings Moderators : Joseph Romano Bethany Young Holt

28. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 FY15 IMPT Convenings Goal: Plan and implement appropriate convenings over the next 12 months so as to better support funder needs in terms of managing current MPT investments and assessing new such investment opportunities. Two major issues currently confronting the MPT field are:  Verification of the hypothetical advantages of MPT products  Complexities of MPT Phase 2b/3 Clinical Trials

29. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Proposed FY15 Convenings Topics  Social-behavioral considerations for MPTs (with WHO)  HC in MPTs follow up (TBD)  Regulatory Issues (TBD)  Environmental impacts of MPTs  MPT Cost-effectiveness modeling (with WHO)  Regionally-tailored MPT webinars (e.g. LAC)  2015 MPT Symposium  Other

30. Steering Committee & Supporting Agency Collaboration Committee Bi-Annual Status and Planning Webinar - 18 November 2014 Moderators : Helen Rees (invited) Bethany Young Holt IMPT Funding Optimization & Enhancement Strategy

31. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Why the IMPT?  Key Challenges Facing the Field: Scientific Social-behavioral Clinical/Regulatory Manufacturing  How does the IMPT help address challenges? Convenings Tools & Guidances  TPPs, Prioritization Survey, Database, etc. Venue for multidisciplinary collaboration

32. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Summary of Funding Strategy Objectives:  Optimization: To increase the effectiveness of existing resources by facilitating successful, well informed collaboration among existing and potential funders.  Enhancement: To engage new potential funding organizations on priority MPT gaps and needs in order to secure field-wide funding to advance the MPT field.  Fundraising: To generate sufficient core funding for the IMPT to serve as Secretariat of the IMPT, and continue its support to facilitate collaboration and organize around the many complicated questions in the MPT field.

33. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 [DRAFT] MPT Funding Opportunity Tool DRAFT Categories

34. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 MPT Investment Tracking: Process  Worked closely with AVAC to look at data collected in the 2013 HIV Resource Tracking Survey  Data from NIH grants database  Preliminary findings show close to $23 Million invested in the MPT field for 2013. Goal: Monitor investment in the MPT field to measure progress and help inform investment prioritizations and gaps.

35. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014  Partner with AVAC’s HIV Resource Tracking Data collection to incorporate more detailed MPT related information.  Distribution of survey to partners working outside of the HIV field.  Key findings will be summarized in an annual MPT Investment Tracking Report and compared to the baseline data. MPT Investment Tracking: FY15 Plan for Moving Forward

36. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Quick Secretariat Update  Evaluation: CAMI Health is developing metrics for tracking progress of the IMPT and the MPT field. Members of the SACC and Steering Committee will be consulted once the evaluation plan is outlined.  CAMI Health Annual Report : Coming Soon!  CAMI Health Staff Update  Scheduling In-Person SACC Meeting

37. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Discussion Reminder:  Please mute your line using *6 if you are not speaking  Press *7 to unmute your line if you have a question or comment. Thank you!

38. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Learn more about MPTs www.CAMI-Health.org & www.MPTs101.org

39. Steering Committee & Supporting Agency Collaboration Committee (SACC) Bi-Annual Status and Planning Webinar - 18 November 2014 Support for this project is made possible by the generous support of the American people through the United States Agency for International Development (USAID) under the terms of the HealthTech Cooperative Agreement #AID-OAA-A-11-00051, managed by PATH. The contents are the responsibility of CAMI/PHI and its partners and do not necessarily reflect the views of USAID or the US Government. Thank You!