Year 1 Report April 1 – June 30, 2021

August 11, 2021 Introduction

The goal of Innovate FP is to expand desirable, affordable, quality contraceptive options to enable women to better meet their changing needs and desires throughout their reproductive lives. The proposed research agenda aligns with three of the specific aims outlined in the original USAID Annual Program Statement: 1) refine existing methods to address method- related reasons for non-use; 2) respond to product-related issues about existing methods; and 3) develop new methods that address method-related non-use and/or fill gaps. Strengthening current and building new partnerships are key to advancing the aims of Innovate FP. The following sections define the activities, accomplishments, and challenges for the period of April 1– June 30, 2021. Plans for the next 3 months (July – September 2021) are included, including updated simple Gantt charts for each activity. Year 1 budgets for these activities and expenditures through June 2021 are provided in Appendix 1.

Aim 1: Refine existing contraceptive methods

Our focus under Aim 1 is to refine and advance knowledge on mid- to long-acting contraceptives, with a specific focus on extending duration and lowering the overall dose of depot medroxyprogesterone acetate (DMPA) injectables. The highest priority is implementing a safety and effectiveness trial of a 6-month DMPA product. 6-month DMPA SC (DMPA XT): pivotal Phase 3 trial Lead: Vera Halpern, MD Goal: To conduct a pivotal Phase 3 trial for stringent regulatory approval of a 6-month subcutaneous (SC) contraceptive injectable (DMPA XT) based on an existing, generic 3-month DMPA intramuscular (IM) formulation. Significance and Impact: Over 40 million women worldwide use injectable contraceptives, including more than one-third of modern method users in sub-Saharan Africa. Current injectables are effective for one to three months, requiring relatively frequent visits for re- injection. However, recent research has documented that many women would prefer injectables that last longer, in part for convenience. Under Envision FP (USAID Cooperative Agreement AID-OAA-A-15-00045), with co-support from the Bill & Melinda Gates Foundation (BMGF), FHI 360 showed that a single SC injection of 3-month DMPA IM (150 mg) suppresses ovulation completely for at least 7 ½ months while reducing dose by half when compared with the current 3-monthly IM regimen. These data provided proof-of-concept that a novel 6-month injectable could be brought to market in a rapid, cost-efficient manner by repurposing an existing DMPA IM product. We also received scientific advice from two European national regulatory agencies and an endorsement of a Phase 3 trial design and regulatory development plan.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 1 With positive study results from a pivotal Phase 3 trial, DMPA XT could be approved as early as 2025/26 by a European regulatory agency, far ahead of other 6-month injectables currently in development. The new product will use the same 150mg/mL vial as the 3-month DMPA IM formulation, and will be co-packaged with an SC syringe. This will keep manufacturing costs low and contribute to a substantially shorter time to market. Approach: We will enroll up to 750 women (at least 25% of them in Europe per EU guidance) willing to use DMPA XT every 6 months as their only means of contraception for 12 months and evaluate efficacy, safety, bleeding changes, and acceptability. Additional important aspects of this study will be to: 1) assess the impact of this lower-dose strategy on bone mineral density; and 2) characterize how pharmacogenomic differences among participants (particularly certain genetic variants) may influence side effects or outcomes. Major milestones include: 1) enrollment completion (Q2 Yr 3); 2) interim analysis when 50% of participants complete 12 months (Q3 Yr 3); 3) follow-up completion (Q4 Yr 4); 4) final analysis and clinical study report (Q2 Yr 5). We bring a substantial financial commitment (co-funding and clinical supplies for the trial) from a pharmaceutical company with WHO-prequalified DMPA IM product and interest in marketing DMPA XT in FP2020 countries. Using their 3-month DMPA IM formulation currently being procured by USAID, we will leverage their WHO PQ dossier to accelerate the clinical trial application (CTA) preparation and study start-up. We will seek an eventual marketing authorization in an EU member country via a hybrid generic application under the decentralized procedure and will develop a product registration and introduction strategy for FP2020 countries during the pivotal trial. We will seek additional funding from other commercial partners, as appropriate, for regulatory submissions and roll-out in non-FP2020 markets/countries if the trial is successful. Activities, Accomplishments, and Challenges in past 3 months: We received protocol approval from USAID in Jun. 2021 and finalized the Investigator’s Brochure and generic consent form. We submitted these study documents to FHI 360’s IRB, PHSC, in Jul. 2021 and received contingent approval pending a few minor revisions to the consent form and protocol. Between Apr. - Jun. 2021, we received revised budgets from the clinical study sites in the Dominican Republic (DR), Chile and South Africa and started drafting subagreements for these sites. We executed a purchase order with Assay, a Clinical Research Organization in the UK, who will assist with regulatory and ethical committee submissions and budget and agreement negotiations for the UK clinical sites. We negotiated budgets with local clinical monitors for monitoring the South Africa, DR and Chile sites. In Jun. 2021, we drafted Case Report Forms. We initiated the electronic Trial Master File (eTMF) and started filing essential documents in preparation for the first internal eTMF QC to be performed in Jul. 2021. We developed the FHI 360 study team RACI and the study-specific training matrix, and started drafting the risk register and project management plan. Plans for the next 3 months: Between Jul. - Sep. 2021, we will finalize site budgets and agreements with the clinical study sites and finalize a subcontract with Assay supporting ongoing regulatory affairs, clinical monitoring and safety management. We will also execute contracts with the local clinical monitors. In Jul. 2021, we will obtain final PHSC

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 2 approval for the protocol and generic consent form and submit the final protocol for translation into Spanish. In Aug. - Sep. 2021, we will prepare IRB submissions for the sites and submit to the local IRBs (Profamilia IRB – Dominican Republic; Scientific Ethical Committee of the Central Metropolitan Health Service – Chile; WITS Human Research Ethics Committee – South Africa; South East Scotland Research Ethics Committee – UK). We will prepare regulatory documents and submit to the UK Medicines and Healthcare products Regulatory Agency (MHRA) between Aug. - Sep. 2021. In Aug. - Sep. 2021, we will evaluate the manufacturing partner’s WHO PQ dossier to develop the Investigational Medicinal Product Dossier (IPMD) portion of the Clinical Trial Authorization (CTA) submission. In Sep. 2021, we will procure clinical supplies and register the study in EudraCT (European Union Drug Regulating Authorities Clinical Trials Database). We will work with our pharmaceutical company partner to generate the Investigational Product labels for the clinical trial vials/packages in Sep. 2021. Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Site selection, preparation, and training • • • • • • • • • • Protocol development • • • • • • IRB submission/approvals • • • • Regulatory submissions/approvals • • Manufacturing partner agreement executed •

DMPA SC Extended use: user and service delivery considerations Leads: Holly Burke, PhD and Rebecca Callahan, PhD This study is being co-funded by the Children’s Investment Fund Foundation (CIFF). Goal: To evaluate and understand market implications, including user, provider, and other stakeholder perspectives, on adding multiple extended DMPA SC products to the method mix. Significance: Understanding the market implications of adding new injectables of varying durations and delivery mechanisms into programs within a similar timeframe is essential to provide an evidence based roadmap for successful product introduction. This work will complement and expand a scoping activity funded by the Children’s Investment Fund Foundation (CIFF) to develop a regulatory strategy and explore the market implications of introducing multiple injectable products. Limited qualitative research has explored provider and other stakeholder perspectives on introducing injectables of varying durations. More data are needed, including from users, in varying contexts to inform introduction decisions. Approach: We will use multiple methods including qualitative interviews and human-centered design (HCD) research and workshops to solicit user and stakeholder opinions, preferences, and suggestions on the prospect of introducing both a 4-month DMPA SC in Uniject and a 6-month DMPA SC injectable (syringe and vial; DMPA XT) to the method mix. For Activity 1, we will conduct in-depth interviews with FP providers, program implementers, policy makers, and others in Nigeria and Uganda to explore opportunities, challenges, and preferences for the

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 3 introduction of multiple new injectable products. For Activity 2, we will conduct triads (discussions with 3 participants) with males/partners, mini focus group discussions (up to 5) with users and facilitate HCD workshops with potential users to explore preferred approaches for providing different duration injectables and types. The workshops will also be used to generate communication strategies and marketing messages for these new products. This activity will be conducted over Years 1 & 2. Activities, Accomplishments, and Challenges in past 3 months: Activity 1 – Over the last period, we incorporated feedback from local IRBs, the National Health Research Ethics Committee, Nigeria (NHREC) in Nigeria and The AIDS Support Organization (TASO) Research Ethics Committee in Uganda, and received study approval on May 20 and May 5, respectively. In addition, approval of the Uganda National Council for Science and Technology (UNSCT) was required and received on Jul. 6. The local study teams were trained on qualitative interviewing techniques, data capture, and the discussion guides. Recruitment, scheduling of interviews, and data collection are all active at the time of writing and anticipated to continue through Aug. 2021. Activity 2 – With CIFF funding, we contracted two design firm partners to conduct Activity 2 data collection in Uganda (Design without Borders) and Nigeria (Scope). Together, the FHI 360 team and design partners worked to finalize the study protocol and data collection instruments that FHI 360 had developed to meet local IRB deadlines for Lagos State University Teaching Hospital (LASUTH) in Nigeria and TASO in Uganda. IRB submissions are targeted for mid-Jul 2021. Plans for the next 3 months: Activity 1 – Over the next three months, we will complete data collection in both countries and begin analysis. Activity 2 – We anticipate obtaining IRB approvals between Aug. – Sep. 2021 in both countries. Once approvals are obtained, we will implement the phase I assessments (rapid qualitative assessments with users) including training the design firm teams on the study tools and ethics considerations. We will also begin planning for phase II, HCD/ideation workshops, which we plan for Nov. 2021. Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Activity 1 – Key Informant/Provider Study Develop protocol and data collection • • • instruments for provider/stakeholder interviews Obtain in-country IRB approval for provider/ • • • stakeholder interviews Conduct provider/stakeholder interviews • • Analyze provider/stakeholder data • •

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 4 Activity 2 – Rapid Assessments and HCD/Ideation

Workshops Develop protocol and data collection • • • • instruments for user HCD research Contract design firm(s) • • Finalize protocol and data collection • • instruments for user HCD research Obtain in-country IRB approval for user HCD research • • Conduct rapid qualitative research with users to • inform HCD workshops

AIM 2: Respond to product-related issues about existing contraceptive methods

Under Envision FP, FHI 360 successfully addressed a wide variety of product-related issues that had potential to create barriers to availability and use. We will use a similar Rapid Response approach under Innovate FP. Our first activity will evaluate field and clinical trial reports of malfunctions of Sayana Press devices to determine programmatic significance. In addition, we will proactively consider how potential non-contraceptive benefits and contraceptive-induced menstrual changes can be adequately addressed in contraceptive research and development.

Rapid response and proactive risk mitigation for contraceptive programs Leads: Markus Steiner, PhD and Elena Lebetkin, MPH Goal: To address product-related issues in the field that affect provider/user perceptions, policies, programs, and/or the supply chain. Significance and Impact: When concerns about contraceptives arise in the field, loss of trust can quickly lead to dramatic disruptions in contraceptive procurement, programs, and use. The rapid response activity supports evidence-based policies and programs by dispelling rumors, quelling anxiety, and filling information gaps. Under Envision FP, our team led 19 responses to address concerns or potential concerns: 14 originating from field requests and 5 in which FHI 360 proactively supplied evidence. Approach: Innovate FP will continue and strengthen our successful Rapid Response mechanism, drawing upon a multidisciplinary team of experts from FHI 360, including our Product Quality and Compliance (PQC) team and our partners, to rapidly and systematically respond to field- based concerns as well as to proactively identify and address issues. Our approaches will include literature reviews, evidence synthesis, data analysis and modeling, document review, new tool development, and product quality assurance. We will also support systematic reviews on product-related issues focusing on topics with direct relevance to our product development portfolio. We will leverage our country offices and work closely with USAID, MOHs, and local partners to address field concerns collaboratively. We will make every effort to work directly with field-based partners in order to build capacity to respond to concerns locally.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 5 Activities, Accomplishments, and Challenges in past 3 months: Couple Year Protection (CYP) literature review and guidance document The Rapid Response Team worked closely with staff from USAID and Avenir Health on the CYP literature review and guidance document. Several drafts were shared for internal USAID review and feedback was incorporated. Caya Diaphragm The Rapid Response Team provided regulatory guidance to the manufacturer on a strategy for a label change that would allow procurement by USAID. A series of meetings were held with the manufacturer and Path/WCG to understand the product’s regulatory status and proposed strategy before devising the new strategy. This strategy was then discussed with FHI 360 Product Quality and Compliance staff as well as a former FDA staff involved in the approval of the Caya diaphragm. Before implementation of the strategy, a final meeting was held with USAID to present the exact wording change to the label. The manufacturer subsequently made the desired changes and is now taking steps to be included in the USAID Product Catalogue. CONRAD trocar During an initial introductory call with the CONRAD “trocar” team on Feb. 26th 2021, Dr. Markus Steiner provided an overview of product development steps, including a clinical trial in Kenya, to obtain the CE Mark for the disposable trocar for Levoplant (formerly named Sino- implant). The disposable trocar is manufactured in China with annual volumes now exceeding 2 million units. After follow-up conversations, USAID approved Dr. Steiner’s coverage for this work on and he is now available to consult with CONRAD upon request. Contraceptive Technology book The team was invited to author two chapters in the 22nd Edition of Contraceptive Technology – Choosing a Contraceptive: Efficacy, Safety, and Personal Considerations (Chapter 3) and Contraceptive Efficacy (Chapter 26). The team held initial conversations with Deborah Kowal, editor, on expectations and timelines (due late Mar. 2022) and received the Word versions of the chapters from the 21st edition to begin reviews. The co-author is currently on maternity leave and upon her return when the scope of work has been defined, a budget for this activity will be submitted to USAID. Plans for the next 3 months: Couple Year Protection (CYP) literature review and guidance document The CYP literature review and guidance document will be formatted as a brief. The dissemination plan for the brief will be led by USAID and supported as appropriate by FHI 360 and Avenir Health. In conjunction with USAID, we are also exploring submitting a Commentary to Global Health: Science and Practice to briefly summarize our approach and results and hyperlink to the full document. Caya Diaphragm We will follow up with the manufacturer of the Caya Diaphragm to see if additional technical assistance is needed regarding USAID procurement of the product. Any additional work would be submitted and approved by USAID.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 6 CONRAD trocar We are on standby and can provide CONRAD technical assistance with any trocar related questions they may have. Contraceptive Technology book The team will begin reviewing and revising Chapters 3 and 26 of Contraceptive Technology. Other The team will continue passive surveillance for field-generated concerns and maintain availability to respond to USAID’s requests. We will specifically keep a close eye on COVID- related concerns as we anticipate supply chain and service disruptions will continue. We will continue to work with USAID to determine the need for additional product briefs and are prepared to develop briefs or any other information products as needed. Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Finalize CYP document • Trocar technical assistance to CONRAD • • • • • Caya diaphragm regulatory strategy input • • • • • • • Passive surveillance for field-generated concerns • • • • • • • • • • • • Respond to USAID requests including field-generated concerns • • • • • • • • • • • • Develop new product briefs as needed in consultation with USAID • • • • • • • • • • • • Monitor need for response due to COVID-19 service and supply chain disruptions • • • • • • • • • • • • Explore need for systematic reviews • • • • • • • • • • • • Revise chapters of Contraceptive Technology • • •

Assessment of Uniject ™ malfunctions among DMPA-SC users Lead: Markus Steiner, PhD Goal: To determine the magnitude and clinical significance of Uniject malfunctions in real-world settings. Significance and Impact: Sayana Press (DMPA-SC delivered in Uniject) is increasing in global popularity. As of Oct. 2019, DMPA-SC is registered for self-injection in more than 50 countries worldwide, and 19 countries have already introduced or are planning to introduce self- injection. Evidence from multiple countries demonstrates the product’s acceptability, efficacy, safety and, when offered through self-administration, significant positive impact on

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 7 continuation. Despite these advantages, trained study staff in FHI 360’s acceptability studies have anecdotally reported Uniject malfunctions, specifically units not expelling drug. Given these experiences, we systematically assessed malfunctions during the Sayana Press Extension (SPE) trial being conducted in Brazil, Chile, and the Dominican Republic. Interim data suggest a Uniject malfunction frequency of 2.5% (n=49) in the trial. Currently only Pfizer’s Sayana Press is available, but a consortium of donors is actively working to develop a generic DMPA-SC product in Uniject with anticipated WHO prequalification as early as 2023. Given the importance of this method, lack of data on Uniject malfunctions among self-injectors and lack of information for providers and users on how to manage malfunctions, we propose a multi-phased activity to identify the types, rates, and clinical significance of malfunctions. Importantly, the findings can provide timely information to the manufacturer currently developing generic DMPA-SC in Uniject. Approach: We will achieve our goal through three primary sub-activities. These are: Activity 1: We will analyze all available Uniject devices that malfunctioned during the SPE trial. In Year 1, we will collaborate with the FHI 360 Product Quality and Compliance (PQC) laboratory to adapt a device testing protocol and will ship stored devices from the three clinical sites to PQC for investigation (i.e., x-ray and other functional tests as indicated) to determine the cause of malfunction. We will complete testing and document the results and recommendations at the end of Year 1. We will also share the malfunctioned devices with Pfizer for further assessment. Activity 2: We will conduct a mixed-method assessment of the experiences of governments and implementing partners (including social marketing organizations) with Uniject malfunctions within their global DMPA-SC in Uniject service delivery programs. We will conduct key informant interviews with medical officers from organizations that use DMPA-SC in their programs and MOH officials with knowledge of DMPA-SC programs to document experiences and assess the clinical significance of Uniject malfunctions using semi-structured interviews and/or brief surveys. Activity 3: The team will monitor pharmacovigilance (PV) signals and informal reports through periodic engagement with medical officers of service delivery organizations and other stakeholders involved in the distribution of DMPA-SC in Uniject. Throughout the work, the team will share information as it emerges with the donors and manufacturers, including Pfizer, as well as service delivery groups. If results warrant, the team will explore potential expansions to this research with service delivery partners and donors. Activities, Accomplishments, and Challenges in past 3 months: For Activity 1, we completed the initial laboratory assessment and were unable to replicate the device malfunctions under a variety of laboratory conditions. We hypothesize that this was because of the lack of back pressure when not injecting into subcutaneous tissue. We began discussing appropriate animal models (e.g., baby pig tissue) but decided to engage and seek input from Pfizer. The team reached out to Pfizer to discuss collaborating on additional laboratory assessments in early May 2021. Pfizer’s Pharmacovigilance Group documented an incidence report and their Drug Safety Group began their investigation with a due date of July 2.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 8 No further work on Activity 2 has been conducted as we were waiting for the report from the Pfizer investigation before we move forward. Plans for the next 3 months: For Activity 1, Pfizer provided a Response Letter in early Jul. noting that the investigation is now closed with no related quality issues identified. We will engage with a small group at USAID to discuss appropriate next steps. Scope and timing of Activities 2&3 are dependent on further discussion with USAID, therefore, the timeline for these two activities may change. Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Activity 1 Ship devices to PQC Lab • • • • Develop Testing Protocol/Amend as appropriate • • • • • • Implement testing • • • • Draft Final Report and share with stakeholders • • • • Activity 2 Compile list of key informants • • Draft mixed method data collection tools • • • • • • • • • Conduct interviews • • Synthesize data • • Draft slide deck and share with stakeholders • • Activity 3 Document reported PV event signals • • • • • • • • • • • • Plan for annual follow-up of PV event reporting • •

Addressing contraceptive-induced menstrual changes in contraceptive R&D Leads: Kate Rademacher, MHA and Amelia Mackenzie, PhD Goal: To ensure that potential contraceptive-induced menstrual changes are adequately addressed in contraceptive research and development. Significance and Impact: Contraceptive-induced menstrual changes (CIMCs) impact users’ lives in both positive and negative ways. CIMCs can be a reason that individuals are dissatisfied with, discontinue, or avoid using hormonal methods and copper IUDs. At the same time, insufficient attention is often paid to the variety of non-contraceptive health benefits of contraceptives, such as the potential to treat menorrhagia, dysmenorrhea, endometriosis and/or other menstrual disorders, as well as to prevent or reduce the risk of iron deficiency anemia and other health outcomes. Reduced bleeding or amenorrhea can also have lifestyle advantages for some women such as increased freedom to engage in work or school activities and/or reduced costs associated with menstrual hygiene products. Consideration of CIMCs and other non- contraceptive benefits needs to be integrated into contraceptive R&D efforts as new products are being developed, evaluated, and introduced.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 9 Approach: Under Innovate FP, our team will leverage ongoing work by FHI 360 and others to support product developers, donors, national governments, and other key stakeholders to ensure that potential CIMCs and other non-contraceptive health benefits are adequately addressed in contraceptive research and development. This work builds upon thought leadership under Envision FP including a technical consultation on CIMCs that took place in Nov. 2020 in collaboration with the USAID-funded Research for Scalable Solutions (R4S) project. Activities, Accomplishments, and Challenges in past 3 months: The Contraceptive-Induced Menstrual Changes (CIMC) Task Force was launched in Apr. 2021 and brought together 28 menstrual health and family planning experts from 18 organizations and 10 countries. With co- funding through the Research for Scalable Solutions (R4S) project, the key Task Force deliverable will be a “Global Call to Action” document with a set of research agendas addressing: 1) measurement and indicators, 2) contraceptive R&D and biomedical research, 3) social-behavioral & user preferences research, and 4) programmatic research. The Task Force includes representatives from USAID, NICHD and BMGF. The project team also provided technical assistance to the clinical teams on the DMPA XT project and the BMGF-funded Cases S biodegradable implant project to develop and revise questions related to CIMCs for their clinical trial CRFs, including questions about the menstrual cycle at enrollment, monitoring CIMCs via daily diaries, and assessing broader changes and perceptions of those changes at follow-up visits. In addition, FHI 360 convened a panel presentation on CIMCs with colleagues from Makerere University, University of Ibadan, and Guttmacher Institute in Apr. 2021 with co-funding from the R4S project as part of the Global Health Science and Practice Technical Exchange. The recording is now available here. Also in Apr. 2021, FHI 360 presented on the CIMC Global Call to Action at a virtual pre-conference workshop for the Population Association of America (PAA) Annual Meeting. During the PAA Annual Meeting in May 2021, FHI 360 organized and chaired a new session on menstrual health and reproductive behaviors. In May 2021, as part of Menstrual Hygiene Day, FHI 360 participated in the virtual Symposium on Menstrual Health and Hygiene in West and Central Africa with co-funding from the R4S project, including participation in a panel discussion titled “Strengthening the integration of menstrual health and hygiene in sexual and reproductive health services.” FHI 360 also provided a summary and presentation recording titled “Contraceptive-Induced Menstrual Changes – A Call to Action” for the conference abstract room. All conference recordings will soon be available on the Soyons Reglos and the French Muskoka Fund websites. Plans for the next 3 months: In Aug. 2021, the draft CIMC Global Call to Action document will be released for community review. The draft research agendas will be made publicly available, and stakeholders in the family planning and menstrual health communities will be engaged to provide input via a survey. Several mechanisms will be used to disseminate this survey including listservs, newsletters, social media, CIMC Task Force networks, Innovate FP and R4S leadership team networks, and communications with specific interest groups. Community feedback will be incorporated for final endorsement of the Global Call to Action by the CIMC Task Force members. In Sep. 2021, the final white paper, “Global Call to Action: Addressing Contraceptive-

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 10 Induced Menstrual Changes in Research, Product Development, Policies, and Programs”, will be disseminated via a webinar and using the channels mentioned previously. The project team will continue to provide technical assistance on CIMCs to our clinical teams, including on the BMGF-funded Levonorgestrel Long-acting Microsphere Injectable (LLMI) project. We will also continue conversations with the clinical teams to determine next steps for developing and validating CIMC indicators for contraceptive R&D research and trials at large. Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Integrate recommendations from CMIC Global Call to action • • • • • • • • • • • into contraceptive R&D activities Task Force on CIMC Global Call to Action • • • • • • •

AIM 3: Develop new contraceptive methods to address method-related non-use and/or fill gaps

FHI 360 and its partners have made significant progress toward the development of novel, long- acting progestin-only contraceptive products including a microneedle patch (MNP) and a biodegradable implant (BDI). Under Innovate FP, we will continue to advance these two products, leveraging funding from other donors. Parallel acceptability research will inform formulation and design decisions.

A 3-6 month progestin-only microneedle patch Lead: Jennifer Ayres, PhD Goal: To develop a discreet, user-initiated long-acting progestin-only microneedle patch (MNP) contraceptive. Significance and Impact: While a variety of progestin-only contraceptives are popular worldwide, additional easy-to-use innovative options could expand choice, improve continuation, and reduce unmet need. Progestin-containing biodegradable MNP delivery systems would offer women truly innovative, discreet contraception allowing simple and safe self-administration without biohazardous waste. Unlike current contraceptive patches which remain in place, after the MNP is applied, the backing is quickly removed, leaving the microneedles embedded in the skin to deliver their payload. Approach: Under Envision FP, we collaborated with Dr. Mark Prausnitz (Georgia Tech) to use his MNP platform to directly load progestin into slowly biodegradable microneedles for 3-6 months contraceptive coverage. [Note: This work leveraged parallel BMGF-funded activities to develop MNPs with rapidly dissolving microneedles containing progestin-loaded microparticles for 6 month contraception.] We evaluated LNG, etonogestrel (ENG) and nestorone (NES) for

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 11 formulation compatibility. LNG has greater compatibility with the fabrication process and yielded slower release kinetics due to its lower solubility in both organic and aqueous media. NES has the greatest solubility and was determined to be incompatible with extended release from MNPs, so development activities were discontinued. ENG has intermediate solubility. We selected LNG for further development; however, we will continue some activities with ENG. We are considering ENG as a back-up active pharmaceutical ingredient (API) and ongoing activities will provide information on how API structure and solubility affect microneedle properties and release characteristics. A 3-6 month MNP for women will need to be larger and have more needles and/or larger needles than those used in the rat in order to deliver a greater amount of drug. Under Envision FP, Georgia Tech conducted a human placebo patch study of 18 MNP designs to evaluate pain and acceptability with rapidly dissolving microneedles varying in number, size and spacing to inform the maximally tolerable limits for these parameters. Under Innovate FP, Georgia Tech will collaborate with Emory University and FHI 360 to conduct a trial to evaluate the safety, tolerability, and biodegradation of placebo MNPs with a slowly biodegradable needle formulation to further inform formulation development as well as the longer-term safety of the slowly biodegradable system (something not assessed in the study of rapidly dissolving MNP designs). We will evaluate approaches to maximize drug loading and control release kinetics while designing patches suitable for human dosing. Georgia Tech will conduct a series of smaller placebo studies to evaluate pain, acceptability, and delivery efficiency of rapidly dissolving needles to inform the feasibility of multiple designs for larger patches. They will also do iterative in vitro dissolution and rat PK studies to optimize the formulation. After selecting a lead candidate for human dosing, we will engage a CRO to conduct a study to evaluate LNG MNP application and PK in a mini-pig model with skin and subcutaneous tissue similar to humans to inform dosing for a Phase 1 trial. We will work with a regulatory consultant to define the scope of pre-Investigational New Drug (IND) activities, have a pre-IND meeting with the U.S. Food and Drug Administration (FDA), and work with a CRO to conduct the recommended IND- enabling studies. Based on the extensive prior use of LNG and excipients utilized in these formulations, we believe minimal toxicology studies will be required. We will seek additional funding to support a Phase 1 trial. Activities, Accomplishments, and Challenges in past 3 months: In collaboration with Georgia Tech and Emory University, we drafted the protocol for the clinical study to evaluate the safety, tolerability, and biodegradation of slowly biodegrading MNPs. We prepared an Integrated Product Development Plan (IPDP), which outlines overall program strategy, and submitted it to USAID in Jun 2021. We also finalized the scopes of work for subawards to Georgia Tech and Emory and we executed the subaward with Georgia Tech, effective Jul. 2021. Plans for the next 3 months: We will finalize the protocol, consent form and questionnaires for the clinical study and submit to the IRB after USAID review. The team at Georgia Tech will manufacture patches for the clinical study and work with Emory to initiate the study in Sep 2021. We will build upon formulation activities started under Envision FP (for ease of reference and comparison, we include activities for both programs in the table below). The team at Georgia Tech will complete optimization of a 1-month ENG patch to increase drug loading and detachment efficiency before evaluating formulations in a 1-month rat PK study. Although LNG

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 12 is the lead candidate for future development, ENG is being considered as a back-up, and this last study with ENG will provide information on how API structure and solubility affect microneedle properties and release characteristics. Georgia Tech will also continue formulation optimization and in vitro release testing for a core shell LNG patch with the potential to achieve a 3-6 month duration. They will continue process optimization, including evaluation of nano- dispensing and melt-casting into MN molds. They will also perform an evaluation of gamma sterilization and initiate preliminary stability testing with 1-month patch formulations to inform the development of the longer-acting patch. Year 1 Implementation Timeline* 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Funded by Envision FP • Analyze data from placebo study to evaluate 18 • • • • • • • • MNP patch designs and issue report • Optimize 1-month ENG patch • • • • • • • • • Rat PK study to evaluate 1-month ENG patch • • • Optimize 3-6 month LNG patch to reduce initial • • • • • • • • • burst and increase duration of release • Conduct in vitro release studies for 3-6 month • • • • • • • • • LNG patch • Optimize 3-6 month LNG patch for human • • • • • • • • • dosing • Develop processes for nano-dispensing into MN • • • • • • molds • Perform preliminary evaluation of gamma • • • sterilization Funded by Innovate FP • Continue formulation optimization and in vitro release testing for 3-6 month patch suitable for • • • human dosing • Continue to evaluate effects of radiation • • • sterilization on LNG patches • Conduct rat PK study to evaluate core-shell LNG • • • patch • Conduct preliminary stability testing for LNG • • • patches • Optimize patch designs for placebo studies • • • • • • Manufacture patches for placebo studies • • • Conduct placebo study to evaluate safety, tolerability, and biodegradation of MNPs • • • (slowly biodegradable needles)

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 13 • Initiate a series of small placebo studies to evaluate larger patch designs (rapidly dissolving • • • needles) • Submit TPP to USAID • • Submit IPDP to USAID • *For reference to reflect the transitional workplan year (FY 21) between Envision FP and Innovate FP, we have provided information on both agreements both in this table. Formulation optimization and sterilization activities that begin under Envision FP will continue under Innovate FP.

A 18-24 month biodegradable implant Lead: Jennifer Ayres, PhD This activity is being co-funded by the Bill and Melinda Gates Foundation. Goal: To accelerate prototype development and shorten the timeline for a FIH trial of an LNG Biodegradable Implant (BDI) with a duration of 18 to 24 months. Significance and Impact: Existing contraceptive implants require removal, which necessitates trained personnel, supplies, and equipment that are often limited in low-resource settings. A BDI would expand choice and provide an innovative option to reduce the removal challenges and burden for users and providers/clinics. Approach: Since 2014, FHI 360 has collaborated with Dr. Mark Saltzman (Yale University) to develop a BDI, with support from USAID and BMGF. This approach utilizes a novel copolymer, poly(ω–pentadecalactone-co-pdioxanone) [poly(PDL-co-DO)], with hydrophilic and hydrophobic components, the ratio of which can be tuned to optimize API release and duration. This copolymer remains mechanically strong over time, an important consideration for removability if desired by the user. The target product profile (TPP) for this product includes an intermediate duration of effectiveness (18-24 months), removability for up to 6 months before the intended duration, and a short tail (preferably less than 6 months) for a predictable return to fertility. To date, we have developed methods for manufacturing LNG BDI implants on a small scale and evaluated formulation and process parameters in vitro and in vivo to optimize release kinetics. For candidate formulations, we have demonstrated biocompatibility in mice (6 months) and sustained release and removability in rats (20 months). We further optimized implant designs to minimize the release tail (inactive copolymer core/progestin shell design) and the initial burst (inactive coating). With BMGF support, we will continue formulation optimization which will be informed by in vitro dissolution studies to characterize LNG release, by experiments to measure polymer degradation and implant strength as a function of incubation time (in vitro), and by a 2-year rat study to evaluate PK, burst, tail, implant degradation, and removability. Under Innovate FP, we will leverage activities funded by BMGF and Envision FP to maximize the likelihood of success and accelerate the timeline to the clinic. Activities will include: 1. Optimization and scaling of both the polymer and implant manufacturing processes: Both polymer and implants are currently fabricated on a lab scale which is not viable for the clinical trial product. We will scale up the polymer manufacturing process and optimize the implant fabrication process that will initially be developed with BMGF funding.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 14 2. Toxicology studies to support regulatory filings: Although the poly(PDL-co-DO)] degradation products are similar to those in approved products, the novel excipient will likely require additional toxicology data. We have engaged toxicology consultants to advise on required IND- enabling studies. We will seek final guidance from the FDA through a pre-IND submission and consultation before initiating the recommended toxicology testing. 3. Additional animal studies: If the optimized formulations are significantly different than those being evaluated in the ongoing PK study, we will conduct a rat PK study to evaluate optimized implant designs manufactured using the scaled process. We will also evaluate PK and removability for lead candidates in mini-pigs as their skin and subcutaneous tissue more closely resembles that of humans. These data will inform dosing and implant removal for the FIH trial. Data generated from these activities will inform a Go/No-Go decision in Year 4, made jointly by FHI 360, USAID and BMGF, to advance to an FIH Phase I trial. If a Go decision is made, we will seek additional funding for manufacture of the clinical trial material and execution of the trial. Activities, Accomplishments, and Challenges in past 3 months: In May 2021, we initiated work with Polysciences, the CMO selected to manufacture the novel polymer to support optimization of the implant fabrication process. The teams at Yale and FHI 360 worked with Polysciences to establish a synthesis protocol, order raw materials and initiate analytical method transfer. We also finalized the scope of work for the subaward with Yale, which will start in Jul 2021. With CTII-2 funding, we continued to monitor the ongoing rat PK study to evaluate release kinetics for both coated and uncoated core-shell implants. The team at Yale continued efforts to adapt their manufacturing methods to accommodate a biodegradable core. After a delay due to challenges with LNG procurement, the team at Yale continued manufacturing implants for studies to evaluate the effects of polymer molecular weight, exposure to gamma radiation, and storage at 40 °C on implant properties and release characteristics. With support from Envision FP, Yale initiated studies to evaluate the degradation of polymer films at temperatures of 37 °C, 50 °C, and 60 °C, which will inform the development of their accelerated dissolution assay and subsequent studies to evaluate implant degradation. We drafted the pre-IND briefing package to request feedback on the planned toxicology studies and submitted the Meeting Request Letter to the FDA. Plans for the next 3 months: We will work with Yale and the selected CMO to transfer analytical methods and begin manufacture of the polymer to support optimization of the implant fabrication process. The team at Yale will continue experiments to evaluate polymer degradation, both in vitro and in vivo; these experiments will inform the timeline for drug release and also complete degradation of the core. With CTII-2 funding, we will continue ongoing studies to characterize in vivo PK, in vitro release, and mechanical properties of implant formulations. The team at Yale will complete manufacture of implants and initiate studies to evaluate terminal sterilization (radiation), stability, and accelerated dissolution conditions. With support from Envision FP, we will finish the preparation of and submit a briefing package to the FDA and then establish plans for IND- enabling toxicology studies based on FDA feedback.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 15 Year 1 Implementation Timeline* 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Funded by BMGF • Complete manufacture of implants for rat PK • • study • Conduct rat PK study • • • • • • • • • • • • Characterize in vitro release, polymer degradation • • • • • • • • • • • • and mechanical strength for implant formulations • Adapt manufacturing methods to manufacture • • • implants with biodegradable cores • Evaluate multiple accelerated dissolution assays • • • • • • • Evaluate effects of terminal sterilization • • (radiation) on implant formulations • Initiate preliminary stability evaluation • • Funded by Envision FP • Prepare and submit briefing package to the FDA • • • • • • • • • • • • Receive written responses from FDA • • Optimize polymer synthesis • • • • • • • Characterize polymer degradation, in vitro • • Funded by Innovate FP • Evaluate CMO’s with capability to scale-up and • • • • • • • manufacture polymer • Scale-up polymer manufacturing process at CMO • • • • • Transfer of analytical methods to CMO • • • • • Continue characterization of polymer degradation • • • • Begin studies to evaluate implant degradation, in • • • vitro and in vivo • Manufacture implants for microstructural analysis • • • • Submit TPP and IPDP to USAID • *For reference to reflect the transitional workplan year (FY 21) between Envision FP and Innovate FP, we have provided information on both agreements in this table, as well as the leveraged BMGF-funded activities.

Potential user and provider acceptability of a biodegradable implant Lead: Rebecca Callahan, PhD This study is being co-funded by the Bill and Melinda Gates Foundation. Goal: To understand user and provider perspectives on a Biodegradable Implant (BDI) to inform product messaging and introduction. Significance and Impact: End user preferences, attitudes, and concerns can inform product development decision-making as well as help plan for eventual product introduction. In 2015, FHI 360 led an assessment of user perspectives on six new contraceptive products under

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 16 development, including a generic BDI. Limited data from this study indicated that some women and family planning providers have apprehensions about the biodegradable nature of the product, including concerns about safety and what happens to the implant when it biodegrades. Although this study provided some insights into the potential acceptability of a generic BDI, because it focused on multiple novel products, we were unable to deeply explore user and provider reactions specific to a BDI. Under Innovate FP we will conduct a dedicated study to explore user and provider perspectives for a contraceptive BDI, including the desired duration of action and acceptable period of non-removability, and explore product characteristics unique to two BDI products in our pipeline. These data will also inform future introduction and communication messaging. The data collected will inform BDI development programs funded by USAID and others. Approach: This research will focus on the TPPs of the two BDIs in FHI 360’s current pipeline. We will also explore with CONRAD opportunities to incorporate relevant questions about the BDI in their portfolio. We will conduct qualitative research in two countries, to be determined in collaboration with USAID. Factors to be considered during country selection include contraceptive method mix including implant use prevalence, public and private sector support for new contraceptive product introduction, and USAID Mission interest in the research project. We will carry out focus group discussions (FGDs) with women and interviews with family planning providers and other stakeholders including Ministry of Health officials and FP program managers to explore perspectives on product attributes, service delivery considerations such as removability, and potential introduction opportunities and challenges. With both users and providers/stakeholders we will explore the biodegradable nature of the product and solicit input on how best to describe the product to inform future marketing and messaging efforts. This work will begin in Year 1, with data collection and results dissemination in Year 2. Activities, Accomplishments, and Challenges in past 3 months: The team selected Senegal and Kenya as study sites and received USAID mission concurrence to proceed with work in Senegal. The Kenya site will be supported exclusively with BMGF funding. An RFP for the design firm partner(s) was posted publicly in May 2021, as well as shared with specific local design firms identified as potential candidates. Questions from bidders were received, collated, and responses shared prior to a final submission deadline at the end of May. The team received a total of 11 proposals and shortlisted two for clarifying calls which are scheduled for mid-July. The team also began outreach in both selected sites with introductions in Senegal with the Ministry of Health and Social Action and the Department of Maternal and Child Health and engagement with FHI 360 country office staff in both countries. Plans for the next 3 months: Over the next month, the study team will finalize the design firm selection(s) and proceed to contracting. In collaboration with the selected design firm(s), we will develop and finalize the study tools (protocol, discussion guides, consent forms) for local IRB submission. The likely local IRBs will be The African Medical and Research Foundation Ethics and Scientific Review Committee (AMREF ESRC) & National Commission For Science, Technology & Innovation (NACOSTI) in Kenya and Le Comité National d'Ethique pour la Recherche en Santé (CNRS) in Senegal. We will also expand outreach in each site to include all relevant stakeholders needed for country buy-in.

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 17 Year 1 Implementation Timeline 2020 2021 Innovate FP Year One Work Plan Q1 Q2 Q3 Q4 October 1, 2020 - September 30, 2021 O N D J F M A M J J A S Explore potential collaboration with CONRAD • • Develop study protocol and data collection • • • • • • instruments Execute contract with local design firms (BMGF • funding) Prepare for study training and implementation •

OUI: a novel on-demand contraceptive Lead: Greg Kopf, PhD Goal: To advance a non-hormonal, on-demand contraceptive product to a FIH clinical trial. Significance and Impact: A significant deficit exists in the method mix for an easy-to-use, non- hormonal, highly effective, “on demand” contraceptive that would meet the needs of women who have infrequent or intermittent sex. An ideal product would be discreet, rapidly, and highly effective, work when used before coitus, last for an extended period, be non-hormonal, and have minor to no side effects with no disruption of the menstrual cycle. The OUI vaginal soft-gel pre-coital contraceptive capsule being developed by Cirqle Biomedical is designed to meet this product profile. Approach: OUI contains a topically-applied biopolymer that rapidly alters the properties of cervical mucus to prevent sperm penetration. FHI 360 has advised Cirqle on their research and development (R&D) activities for three years. Cirqle has received funding from multiple sources, including the Reproductive Health Investors Alliance (RHIA Ventures), the Bioinnovation Institute (BII), Eurostars, and the National Institute of Child Health and Human Development (X01 grant). One donor, BII, has offered a limited 1:1 match on additional funds raised. Through Innovate FP we propose to leverage these funds and support activities to accelerate OUI to a Phase 1 trial. Specific activities will include: 1) optimization of the pre- clinical formulation in the ewe model (imaging biomarker testing for efficacy; fertility trial); 2) testing of the delivery device in the ewe model; and 3) formulation and soft-gel capsule development for human use. At the completion of these activities, Cirqle will have strong in vivo proof of concept for OUI in the ewe model (a preferred animal model for studying sperm cervical mucus interactions), will have demonstrated its biocompatibility, and will evolve from a pre-clinical formulation to a GMP-manufactured product with its design locked and ready for a Phase 1 trial. OUI will be positioned to enter a clinical trial as part of the path to market for vaginal barrier contraceptives outlined by the FDA. Activities, Accomplishments, and Challenges in past 3 months: During these past few months, we continued to negotiate subaward language which would be mutually acceptable to FHI 360 and Cirqle but have been unsuccessful. Cirqle has relayed concerns to us that their investors are not comfortable with the language that we have proposed. As a result, we have terminated

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 18 our project with them. We will continue to monitor their progress with the hope that there may be opportunities for collaboration in the future. As of June 30, 2021, this activity closed.

OUI: user-centered design Leads: Rebecca Callahan, PhD and Amelia Mackenzie, PhD This activity is co-funded by Cirqle Biomedical. Goal: To solicit user input on the design and delivery of a novel, on-demand contraceptive. Significance and Impact: OUI is a unique, user-controlled, non-hormonal product concept which would fill a gap in the method mix for a non-hormonal, on-demand product. Input from potential users is needed at this early stage to ensure the product is optimally designed to meet user needs and preferences. User feedback will inform design of the delivery “capsule” and fill formulation and will be used to generate future product introduction and marketing messages. Approach: In Year 1, we will conduct a systematic review of the contraceptive and HIV prevention research for lessons learned related to the acceptability of and preferences for vaginal delivery systems and begin planning for human-centered design (HCD) workshops in two countries. These workshops, planned for Year 2, will be preceded by rapid qualitative data collection in each country to better understand the potential market for a user-initiated, on- demand contraceptive as well as to inform the content of the design workshops. We will work with one or more design firms with local representation in the selected countries to conduct the workshops and closely involve Cirqle Biomedical in implementation, which has pledged limited co-funding for this activity. Activities, Accomplishments, and Challenges in past 3 months: Work was paused on this activity awaiting key decisions on the OUI development project. The OUI development project was terminated (as described above) and this activity was cancelled. As of June 30, 2021, this activity closed.

Project Management and Monitoring, Evaluation & Learning

Lead: Amanda Troxler; Operations Manager In an effort to ensure that Innovate FP project activities are completed on time and within budget, FHI 360 has a centralized hub of operations for project management as well as monitoring, evaluation, and learning. These functions work together to serve as a feedback loop for the status of individual activities in support of project planning and reporting requirements as well as to identify opportunities for learning and project efficiency. Project management will be provided at both the specific activity and overall project levels. Innovate FP project management will be responsible for ensuring that all award and reporting requirements to USAID are met and will serve as a liaison between USAID and the activity-level project managers, communicating issues related to timeline and budget. The Innovate FP project management team will submit international travel plans to USAID for approval on a

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 19 quarterly basis. In addition, the team has developed a policy compliance plan and shared with USAID. The team also worked with gender experts at FHI 360 to develop a gender strategy, which was approved by USAID. For any activity that requires mission concurrence, Innovate FP project management will work with USAID/Washington to obtain concurrence prior to initiation of in-country activities. Environment Examination (IEE) and Environmental Mitigation and Monitoring Plans (EMMP) are complete and updates will be provided as necessary. Monitoring, evaluation, and learning (MEL) staff will focus on implementing the MEL Plan in close collaboration with project management, the full team, and USAID. The MEL approaches include the indicators, outcome mapping, learning, and evaluation. M&E staff will also assist with the Key Results Reporting, Management Reviews and regular reporting, coordinating closely with the project management team. Innovate FP is committed to supporting USAID's goal to move countries toward self-reliance. This workplan includes two primary efforts to support this goal: 1) research capacity building for partner institutions and investigators in low- and middle-income countries (LMICs); and 2) development of technologies that have the potential to create health systems savings for LMICs. In Year 1, we will be selecting LMIC-based sites and partners to contribute to design and to implement the planned research program, which includes human-centered design and acceptability studies as well as clinical trials. As we engage with these potential partners, we will assess their capacity needs and look for opportunities for the Innovate FP project to seamlessly incorporate capacity development into the partnerships. In addition, as issues arise under the Rapid Response mechanism, we will make every effort to work directly with field- based partners in order to build capacity to respond locally. The refined and new technologies that are the focus of Innovate FP will both expand contraceptive options and have the potential to reduce costs for countries. For example, DMPA XT would provide an option of fewer doses per year and fewer visits to health facilities for over 40 million women worldwide who currently use injectable contraception. A biodegradable implant would reduce the removal requirement and therefore the need for trained personnel, supplies, and equipment compared to current contraceptive implants. The contraceptive microneedle patch, as a self-administered method with no biohazardous waste and a target duration of 3 to 6 months, has the potential to enhance self-care and reduce health systems costs when compared to many other methods. Activities, Accomplishments, and Challenges in past 3 months: The Innovate FP project management team continued to collaborate with project teams and partners to launch activities and execute agreements. We worked with USAID/Washington to seek mission concurrences. We launched the Innovate FP Twitter handle in May 2021. We submitted the second Innovate FP progress report that covered Jan. – Mar. 2021. We made plans to efficiently collect MEL information from partners and project teams that will be reported to USAID in the Year 1 annual report. We continued to have monthly meetings with USAID to provide updates and review upcoming plans. Plans for the next 3 months: We will continue working with teams to execute agreements. We will continue preparations for a virtual external review committee meeting for the product

FHI 360 Innovate FP Year 1Report (Apr-Jun 2021) Submitted August 11, 2021 Cooperative Agreement Number: 7200AA20CA00016 Page 20 development programs in Fall 2021. The project management team will keep monitoring activity budgets and expenditures along with activity milestones.

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