Summary of Precision BioSciences Conference Call Company Overview - **Company**: Precision BioSciences (NasdaqCM:DTIL) - **Industry**: In-vivo gene editing - **Location**: Durham, North Carolina - **Focus**: Developing gene editing therapies for chronic hepatitis B and Duchenne muscular dystrophy (DMD) [2][3][4] Key Programs PBGene-HBV (Hepatitis B) - **Target Population**: 300 million people globally with chronic hepatitis B [2] - **Current Status**: Program initiated in the clinic late 2024, with ongoing data generation throughout 2025 and into 2026 [3][4] - **Mechanism**: Aims to eliminate cccDNA, the root cause of hepatitis B, rather than just reducing S antigen levels [9][10][12] - **Clinical Trial**: Phase 1 trial named "Eliminate B" with three cohorts, focusing on safety and efficacy [13][14] - **Safety Profile**: Well-tolerated across all doses, with manageable side effects [15][20] - **Data Trends**: Early cohorts show promising reductions in S antigen levels, with cohort three demonstrating sustained reductions [16][18] - **Future Plans**: Completion of cohort three dosing, potential to stop nucleoside analogs, and test for a cure [20][21] PBGene-DMD (Duchenne Muscular Dystrophy) - **Target Population**: Affects boys with a genetic disease leading to muscle loss and early mortality [21][22] - **Current Status**: IND filing expected by the end of 2025, with clinical trials anticipated to start in early 2026 [25][26] - **Mechanism**: Gene editing approach targeting mutations in exons 45 to 55, potentially benefiting up to 60% of DMD patients [22][24] - **Clinical Trial Design**: Phase 1, 2, 3 study design with a focus on safety and efficacy [25][26] Financials - **Recent Financing**: Raised $75 million from existing and new investors, providing a cash runway through 2028 [4] - **Investment Strategy**: Focused on two key programs to maximize capital efficiency and create value inflection points [35] Market Context - **Unmet Needs**: Both hepatitis B and DMD represent significant unmet medical needs, with current treatments lacking effectiveness [21][22][27] - **Competitive Landscape**: Current standard of care for hepatitis B involves nucleoside analogs, which do not address cccDNA, resulting in low functional cure rates (1%-3%) [29][30][31] Strategic Partnerships - **PBGene-HBV**: Potential for strategic partnerships for commercialization, especially for larger phase three trials [32] - **PBGene-DMD**: Opportunities for partnerships exist, but the company is capable of advancing this program independently [33] Future Outlook - **Data Readouts**: Anticipated data readouts for both programs in 2026, with potential for a Biologics License Application (BLA) for DMD by the end of 2028 [26][27] - **Investor Engagement**: Emphasis on demonstrating the effectiveness of gene editing to attract further investment and partnerships [35]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company's cash, cash equivalents, and marketable securities were approximately $707.1 million, down from $861.7 million as of December 31, 2024, reflecting normal operational expenses and nonrecurring costs associated with portfolio prioritization and workforce reduction [23][24] - Collaboration revenue for Q1 2025 was $16.6 million, compared to $28.9 million in Q1 2024, primarily due to a decrease in revenue under the Avansel license agreement [24] - R&D expenses were $108.4 million in Q1 2025, down from $111.8 million in Q1 2024, driven by lower employee-related expenses and stock-based compensation [25] Business Line Data and Key Metrics Changes - The company has dosed the first patient in its Phase 3 studies for hereditary angioedema (HAE) and hereditary ATTR with polyneuropathy, indicating significant progress in its clinical pipeline [9][10] - Enrollment in the global Phase 3 HALO study for HAE is progressing rapidly, with expectations to complete enrollment by the end of Q3 2025 [17][18] - The global Phase 3 MAGNETUDE study for ATTR with cardiomyopathy is also ahead of schedule, with over 90 sites actively enrolling patients [10][21] Market Data and Key Metrics Changes - The company is observing significant interest from both investigators and patients across its programs, indicating a high unmet need in the market for effective therapies [9][10] - The FDA granted RMAT designation for NexSee for the treatment of ATTR with cardiomyopathy, which will facilitate earlier engagement with the FDA [10][21] Company Strategy and Development Direction - The company is focused on operational excellence and aims to offer life-changing benefits through one-time therapies for severe diseases [8] - Intellia is building critical commercial foundations to bring its therapies to market quickly, with plans to file its first BLA in 2026 [14] - The company is monitoring the regulatory environment closely but has not experienced any tangible changes in its interactions with the FDA [13][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in meeting or exceeding regulatory timelines and objectives, with a strong relationship with the FDA [13][14] - The company anticipates a year-over-year decline in GAAP operating expenses of 5% to 10% and expects its cash balance to fund operations into the first half of 2027 [26][42] - Management highlighted the potential for significant value creation from its lead programs and the importance of maintaining a solid balance sheet [23][24] Other Important Information - The company is restructuring its real estate portfolio to reduce costs and simplify operations, expecting nearly $50 million in cash savings from a smaller footprint [39][41] - The company is actively considering non-dilutive financing options as it approaches commercialization, including collaborations and royalty transactions [50][51] Q&A Session Summary Question: Can you provide updated metrics regarding the patient baseline characteristics in the MAGNETUDE Phase 3 trial? - Management expects more than 50% of patients to be on tafamidis in the study, which is important for demonstrating a benefit over existing treatments [30] Question: What should we expect in terms of cash burn in the next 12 to 24 months? - The average cash use is estimated to be about $95 million per quarter, with a focus on efficient operations and significant milestones ahead [35][42] Question: How should we think about the launch dynamics for the first in vivo gene editing therapy? - The company is well-positioned for an efficient market entry post-approval, with a straightforward outpatient infusion process [54][56] Question: How are you thinking about pricing for your molecules given the competitive landscape? - The company aims to price its therapies competitively while providing significant value to patients and the healthcare system [60][89] Question: Can you discuss the impact of recent drug approvals on enrollment in the MAGNETUDE study? - Enrollment remains brisk despite the introduction of new drugs, as the company’s therapy offers distinct benefits [96][100]