Summary of Arrowhead Pharmaceuticals (ARWR) Conference Call Company Overview - **Company**: Arrowhead Pharmaceuticals (ARWR) - **Event**: 2025 Conference at Cantor's Global Healthcare Conference - **Date**: September 04, 2025 Key Priorities and Upcoming Events - **MAPT Clinical Trial**: Launching the first CNS drug administered via subcutaneous injection [3] - **PCSK9 ApoC3 Dimer**: Expected to enter the clinic, targeting ASCVD [4] - **Blazaran PDUFA Date**: Scheduled for November, marking a transition to a commercial company [4] - **Data Releases**: Anticipated data on MAPT and dimer by mid-2026 [5] Regulatory and Commercial Strategy - **Regulatory Interactions**: Positive discussions with regulators, no slowdown reported [6] - **Commercial Preparations**: Commercial team fully established and in training for FCS launch in November [7] Competitive Landscape - **SHTG Market**: Acknowledgment of competitor data, emphasizing the importance of education in the market [8] - **Pricing Strategy**: Discussion on pricing for Plazasiran, suggesting it may be higher than typical cardiovascular drugs due to its unique application [9][10] Clinical Trials and Data Expectations - **Shasta Trials**: Focused on triglyceride lowering, with Shasta-five designed to show effects on pancreatitis [11][12] - **Market Addressability**: Targeting patients with triglycerides above 800, estimated at one million in the U.S. [17][18] Product Differentiation - **Efficacy Comparison**: Plazasiran showed an 80% reduction in triglycerides compared to a competitor's 40% [23] - **Safety Profile**: Claims of superior safety and less frequent dosing compared to competitors [23] Obesity Portfolio - **Dual Targets**: ALK7 and Inhibin E targeting the activin pathway, with potential for both to advance based on clinical data [34] - **Market Positioning**: Potential for use as monotherapy or in combination with GLP-1s for obesity treatment [38] Business Development and Partnerships - **Partnership Strategy**: Focus on maintaining wholly owned assets while exploring partnerships for non-core assets [42][45] - **Recent Deal with Novartis**: $200 million upfront for a preclinical asset, indicating strong interest in CNS applications [46] Financial Outlook - **Cash Runway**: Sufficient cash to sustain operations until 2028, with expectations for further business development [59] Conclusion - Arrowhead Pharmaceuticals is positioned for significant developments in the CNS and metabolic disease markets, with a clear strategy for clinical trials, regulatory interactions, and commercial preparations. The company is focused on leveraging its innovative drug delivery platforms and maintaining a competitive edge through effective differentiation and strategic partnerships.

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash, cash equivalents, and short-term investments totaled $413.4 million [36] - Collaboration revenue for Q4 2024 was $54.2 million, compared to $15.2 million for the same period in 2023, while total collaboration revenue for the year was $100.6 million, up from $97.1 million in 2023 [37] - Total research and development expenses for Q4 2024 were $46.5 million, down from $47.7 million in Q4 2023, and total R&D expenses for the year were $185.9 million, compared to $192.1 million in 2023 [38] Business Line Data and Key Metrics Changes - The company is advancing two first-in-class late-stage clinical programs developed in collaboration with GSK, focusing on neurodegenerative disorders [9] - The pivotal Phase 3 trial in frontotemporal dementia with progranulin gene mutation is expected to read out later this year [10] - The ongoing PROGRESS-AD Phase 2 trial of AL101 in early Alzheimer's disease is expected to complete patient recruitment by early 2025 [10] Market Data and Key Metrics Changes - The company is targeting high unmet medical needs in neurodegenerative disorders such as frontotemporal dementia, Alzheimer's disease, and Parkinson's disease [7] - The proprietary Alector Brain Carrier (ABC) platform aims to enhance the delivery of therapeutics to the brain, improving efficacy and safety [9] Company Strategy and Development Direction - The company is focused on discovering and developing disease-modifying therapies for neurodegenerative disorders [7] - Alector aims to build an integrated biotechnology organization combining expertise in genetics, immunology, and neuroscience with drug discovery and clinical development capabilities [7] - The company plans to hold a virtual educational event in Q2 2025 to share additional preclinical data on its programs [35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential for Latozinemab to provide a path to full approval based on the totality of evidence, including clinical endpoints and biomarkers [20][99] - The company remains committed to making data-driven decisions that create sustainable value [10] - Management highlighted the importance of targeting early symptomatic populations for greater clinical benefit in neurodegenerative disease treatments [42] Other Important Information - Alector received a $1.7 million grant from the Michael J. Fox Foundation for Parkinson's Research to support research on GPNMB [34] - The company is advancing a preclinical pipeline that includes candidates targeting amyloid beta and tau pathology [30][33] Q&A Session Summary Question: Regarding the INFRONT study and patient enrollment - Management confirmed that they intentionally targeted early symptomatic populations and capped enrollment for more progressed patients to enhance efficacy [44][45] Question: On AL101 and its relation to INFRONT-3 - Management indicated that there is no significant read-through from the TREM2 trial to AL101 due to differing mechanisms, but they are optimistic about the biomarkers used in both studies [57][66] Question: About the ABC platform and its differentiation - Management highlighted the versatility and tunability of the ABC platform compared to others, emphasizing its ability to optimize efficacy and safety [75] Question: On siRNA versus ASOs - Management noted that siRNA may offer better on-target activity and fewer side effects compared to ASOs, with ongoing testing to determine efficacy [82] Question: Regarding the INFRONT-3 study power and data maturity - Management confirmed that the study is powered for approximately 90% to detect a 40% slowing of disease progression, with comprehensive data expected at the end of the study [93][95]

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash, cash equivalents, and short-term investments totaled $413.4 million [36] - Collaboration revenue for Q4 2024 was $54.2 million, up from $15.2 million in Q4 2023, while total collaboration revenue for the year was $100.6 million compared to $97.1 million in 2023 [37] - Total research and development expenses for Q4 2024 were $46.5 million, down from $47.7 million in Q4 2023, and for the year, they were $185.9 million compared to $192.1 million in 2023 [38] - Total general and administrative expenses for Q4 2024 were $15 million, slightly up from $14.9 million in Q4 2023, and for the year, they were $59.6 million compared to $56.7 million in 2023 [38] Business Line Data and Key Metrics Changes - The company is advancing two first-in-class late-stage clinical programs developed in collaboration with GSK, focusing on neurodegenerative disorders [9] - The pivotal Phase 3 trial in frontotemporal dementia with progranulin gene mutation is expected to read out later this year [10] - The ongoing PROGRESS-AD Phase 2 trial of AL101 in early Alzheimer's disease is expected to complete patient recruitment by early 2025 [10] Market Data and Key Metrics Changes - The company is targeting high unmet medical needs in neurodegenerative disorders such as frontotemporal dementia, Alzheimer's disease, and Parkinson's disease [7] - The company anticipates realizing a significant portion of its potential in 2025, with a focus on data-driven decisions to create sustainable value [10] Company Strategy and Development Direction - The company aims to discover and develop first or best-in-class disease-modifying therapies for neurodegenerative disorders [7] - The proprietary Alector Brain Carrier (ABC) platform is central to the company's strategy, enhancing the delivery of therapeutics to the brain [9] - The company is committed to advancing its preclinical pipeline, including programs targeting amyloid beta and tau pathology [33] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential for Latozinemab to provide a path to full approval based on the totality of evidence, including primary clinical endpoints and biomarkers [20][99] - The company remains optimistic about the upcoming readout of the Phase 3 trial and the potential for significant clinical benefits [10][124] Other Important Information - The company received a $1.7 million grant from the Michael J. Fox Foundation for Parkinson's Research to support research on GPNMB [34] - A virtual educational event is planned for Q2 2025 to share additional preclinical data on the ABC platform [35] Q&A Session Summary Question: Regarding the INFRONT study and patient enrollment - Management confirmed that they intentionally targeted early symptomatic populations and capped enrollment for more progressed patients to enhance efficacy [44][45] Question: On AL101 and its relation to INFRONT-3 - Management indicated that there is no significant read-through from the TREM2 trial to AL101 due to differing mechanisms [57][66] Question: About the ABC platform and its differentiation - Management highlighted the versatility and tunability of the ABC platform compared to competitors, emphasizing its potential for optimized efficacy and safety [75][78] Question: On siRNA versus ASOs - Management noted that siRNA may offer better on-target activity and fewer side effects compared to ASOs, with ongoing testing to determine efficacy [82] Question: Regarding the INFRONT-3 trial design and patient enrichment - Management explained the challenges in patient enrichment and the decision to focus on symptomatic patients based on observed progression rates [120][121]