Alpha Clinic Network Expansion for Cell and Gene Therapies

The USC+CHLA Alpha Clinic (AC) aims to be a leader in advancing and supporting the development of cell and gene therapies for people from all backgrounds. During the current reporting period, we: • launched the operational infrastructure, • enhanced translational and clinical support capabilities, • expanded our collaborative relationships with our investigators as well as other ACs specializing in cell and gene therapies, • developed and offered new training and educational programs, and • generated a comprehensive patient outreach and community engagement concept. Below is a description of our progress and impact in three main areas. Clinical Trial Operations: Through collaborative efforts with the Southern California Clinical and Translational Science Institute (SC CTSI), Norris Comprehensive Cancer Center and the AC network, we created clinical trial intake protocols to support clinical trial activation. Our AC also assisted several investigators and companies in the preparation of clinical study proposals and product manufacturing. Our Good Manufacturing Practice (cGMP) facility has made significant strides by securing the CIRM INFR5 funding to enhance manufacturing capabilities and by joining the CIRM manufacturing consortium. Our group continues to meet regularly to discuss AC operational plans, team progress, and community engagement planning. We are currently supporting three active trials at USC and nine at CHLA. USC clinical trial progress and outcomes: At USC, the three trials are in the initial stages of activation. The Regenerative Patch Technologies trial should commence recruitment by September 2024. The Neurona Trial is pending IRB approval for recruitment and the team is working with our cGMP facility for processing the therapeutic product. The AC team has linked Abata Therapeutics with an eligible and interested principal investigator, and they are currently assessing site feasibility. CHLA clinical trial progress and outcomes: Trials at CHLA are focused on CAR T-cell therapy for childhood leukemia. To date the CIRM AC team has assisted with project oversight and logistical support, including biospecimen coordination. Support will be expanded when the AC Clinical Research Care Coordinator is fully hired. Education: 1. Cell and Gene Therapy Development Content: This annual 4-unit course provides training in cGMP manufacturing, quality management, and regulatory science related to cell therapy, complemented by hands-on training in our laboratories. Participants also engage in practical case studies during 15 weekly sessions over a four-month period. Impact: The first offering was Spring 2023. Nine participants reported significant increases in understanding of translational requirements from the in-depth case studies and lectures/discussions with industry representatives and local expert instructors. There are currently 13 participants registered for Spring 2024. 2. Innovations in Regenerative Medicine Content: This all-day symposium was co-sponsored by the CIRM AC and the Regulatory Support core of the SC CTSI. Experts from academia, government, and industry provided updates in regulatory aspects of regenerative products, including case studies in orthopedics and ophthalmology, as well as target identification for gene therapy and cell therapy manufacturing. Impact: 82-96% of the 122 attendees had positive survey responses. Participants found the information useful, plan to implement it and are likely to recommend it to others. 3. International Conference on Relapse After Transplant and Cellular Therapy Content: This 6th annual meeting of the ASTCT/EBMT was supported by a CIRM EDUC1 grant to AC site PI, Dr. Alan Wayne. The Conference brought together internationally renowned experts to share their knowledge and current research relative to the biology, natural history, prevention, and treatment of relapse with over 250 participants from around the world. Impact: The majority (96%) of survey respondents agreed that the conference sufficiently met learning objectives, offering new information and skills to overcome treatment barriers, provide patient-centered care, and improve patient outcomes (https://www.astct.org/Attend/ASTCT-EBMT-Relapse-Conference). Patient Outreach & Community Engagement: Progress: We have developed a dual strategy for community outreach. One component will be focused on engaging and educating the lay community on cell and gene therapy in partnership with the SC CTSI. The second component will focus on engaging community health care providers in underserved communities in South Los Angeles. We are providing community outreach support for the Regenerative Patch Technology trial in macular degeneration mentioned above. We are also in discussion with other ACs on development of aligned and complementary approaches to community outreach and engagement. Impact: Our community outreach efforts are in the planning phase, so we do not have specific impact to report yet.

The USC+CHLA Alpha Clinic (AC) aims to be a leader in advancing and supporting the development of cell and gene therapies for people from all backgrounds. Below is a description of our progress and impact in four main areas in the current reporting phase: Translational Development and Regulatory Support: Proposal Development. Progress: We supported 4 CIRM grant applications of internal researchers and 1 CIRM Community Center of Excellence applicant, focusing on community engagement and trial support resources at USC+CHLA. Impact: Our support helped investigators translate new therapies towards inclusive clinical trials and to expand the cell and gene therapy trial (CGT) infrastructure in California. Process Development & Product Manufacturing. Progress: Our cGMP facility received a Drug Manufacturing License from the California Department of Public Health in May 2024 and is developing manufacturing solutions for 6 new clinical trials. Impact: Expansion of product manufacturing helps to accelerate translation of potential cell and gene therapies to testing in clinical trials. Regulatory Support Services. Progress: In partnership with USC’s Regulatory Science Program, the AC has created a portfolio of regulatory support to help USC+CHLA investigators navigate the regulatory landscape for CGT trials. Impact: Improved regulatory support will help researchers bring their inventions quickly to clinical trials and ultimately clinical care. Clinical Trial Operations: Trial Support Optimization. Progress: The AC, the Norris Comprehensive Cancer Center (NCCC) and Department of Pathology established a working group to best support CGTs at USC. We defined workflows and included AC staff in the Blood and Marrow Transplant (BMT) lab to support trial initiation. Impact: Optimized workflows and alignment of responsibilities helped us rapidly expand our support for CGT trials while ensuring highest quality standards. Expansion of Clinical Trial Portfolio. We have grown rapidly and are now supporting 38 clinical trials, up from 15 based on last year’s annual report. At USC, we are currently supporting 16 trials including testing of treatments for macular degeneration, epilepsy, multiple sclerosis, and various cancers. At CHLA, we are currently supporting 22 trials in a range of pediatric conditions including hemoglobinopathies, hemophilia, cancer, and soon to open, rheumatologic diseases including lupus. Impact: Expansion of our trial portfolio will bring more treatments to clinical use in different disease areas. Education: Cell and Gene Therapy Development – From Research to Clinic. Progress: Fifteen students enrolled in the 4-unit course in 2024, bringing the total to 24 students in this reporting period. The course is now officially included in USC’s Department of Stem Cell and Regenerative Medicine curriculum (SCRM 516). Impact: Feedback obtained through a survey indicates that the course is excellent and expanded the participants’ CGT knowledge and skills. Workforce Education Activities. Progress: AC team members participated as guest lecturers in undergraduate and master’s courses and in a professional development day for high school teachers. We are also training 4 CIRM COMPASS program fellows in 1-year long internships (3 at cGMP facility, 1 in community engagement (CE) group). Impact: Training helps raising awareness of the challenges and opportunities in CGT and to prepare future workforce. Patient Outreach & Community Engagement: Alpha Clinic Network CE Working Group. Progress: We launched a monthly CE workgroup for the AC network and are sharing best practices for CE, DEI and clinical outreach. Impact: Participating AC teams will have strong resources for engaging the diverse communities of California in local and collaborative clinical trials for CGT. Provider Landscape Analysis. Progress: The AC team conducted interviews with providers in community clinics across LA County to learn about their experience with clinical trials. Key findings were summarized in a research brief (shared with the AC network and providers). Impact: This work helps CGT researchers better understand community providers’ knowledge and attitudes about trial participation. Clinical Trial Specific Outreach. Progress: In partnership with the USC Race and Equity Center, the USC+CHLA AC created a strategy for community and provider outreach for a CIRM CLIN2 trial in macular degeneration with Patch Technologies. The AC conducted interviews with initial referral sites that guided creation of study recruitment materials. Impact: Helped with the patient referral process for trial enrollment. Community Engagement. Progress: We participated in 2 panels, 1 round table discussion, and taught at different events (see education section). We also helped a large Federally Qualified Health Center with their application to become a CIRM Community Center of Excellence. Impact: Our CE efforts help to connect with the community and to learn from each other.