prime medicine(PRME) - 2025 Q2 - Quarterly Results

Company Overview and Strategy This section outlines the company's strategic vision, mission, and future milestones, emphasizing its commitment to developing curative genetic therapies Forward Looking Statements This section contains standard forward-looking statements, cautioning that the presentation includes projections and expectations about future events, such as program development timelines, clinical trial results, and financial performance. These statements are based on current information and are subject to risks and uncertainties, and the company undertakes no obligation to update them - The presentation includes forward-looking statements regarding strategy, program development, clinical trial timing (IND/CTA filings for AATD and Wilson's Disease in mid-2026), potential of Prime Editing, and financial runway[2] - The company disclaims any obligation to update these statements and warns that actual results could differ materially from expectations due to various risks described in their SEC filings[2] Company Mission and Strategic Roadmap Prime Medicine aims to provide safe, effective, and curative treatments for diseases. The company outlines a strategic evolution from its 2019 discovery phase to achieving clinical validation between 2024-2026, with a focus on generating clinical data for multiple programs and leveraging platform modularity. Key upcoming milestones include filing INDs/CTAs for Wilson's Disease and AATD in 2026, with initial clinical data expected for both in 2027 - The company's mission is to develop safe, effective, and curative treatments that offer lifelong benefits to patients[4] Strategic Roadmap and Key Milestones | Year(s) | Key Objectives | | :--- | :--- | | 2025 | Prepare Wilson's Disease and AATD for 2026 clinical entry. Leverage business development. Build on initial positive clinical data from PM359 in CGD | | 2026 | File IND/CTA for Wilson's Disease (1H 2026) and AATD (mid-2026); initiate Phase 1 trials. Share in vivo proof-of-concept data for Cystic Fibrosis (CF) | | 2027+ | Announce initial clinical data for Wilson's Disease and AATD. File IND/CTA for CF and initiate Phase 1 trials. Relaunch programs in neurology and other large indications | - A core part of the strategy is to secure additional strategic partnerships to accelerate the pipeline and strengthen financial resources[9] Prime Editing Technology Platform This section details the Prime Editing technology, highlighting its broad capabilities, differentiated safety profile, and modularity as a versatile gene editing platform Platform Capabilities and Clinical Proof of Concept Prime Editing is presented as a versatile gene editing technology capable of a wide range of edits, from small base pair corrections to large gene insertions (PASSIGE™). The company reports initial clinical proof of concept with its PM359 program for Chronic Granulomatous Disease (CGD). Data from the first two patients showed rapid engraftment, restoration of protein function (DHR positivity) to levels 3-4 times the therapeutic threshold, and improvement in inflammatory markers, with no serious adverse events attributed to PM359 - Prime Editing is designed with broad capabilities, including point mutation correction, insertions, deletions, and targeted full gene insertion (PASSIGE™)[11][12] PM359 for CGD - Initial Clinical Data Highlights | Metric | Result | | :--- | :--- | | Safety | Tolerable conditioning, no serious adverse events attributed to PM359 | | Engraftment | Rapid neutrophil and platelet engraftment within 2-3 weeks | | Efficacy (DHR) | Patient 1 reached 71% DHR positive neutrophils by Day 60 | | Efficacy (DHR) | Patient 2 reached 66% DHR positive neutrophils by Day 30 | | Inflammation | Patient 2 showed normalization of fecal calprotectin (inflammation marker) | Differentiated Safety Profile and Platform Modularity Prime Editing is highlighted for its highly differentiated safety profile, characterized by the absence of detectable double-strand breaks, off-target edits, bystander edits, or large chromosomal rearrangements in lead programs. This contrasts with potential issues like indels and translocations observed with Cas9 nuclease. The platform's modularity, where components like Prime Editors, delivery systems, and manufacturing processes can be reused across different programs, is positioned as a key advantage that de-risks development and accelerates program advancement - The platform demonstrates a strong safety profile with no detectable double-strand breakage, off-target edits, or bystander edits in lead programs[18][19][20] - In studies on CD34+ cells for the CGD program, no off-target editing was detected, and no large deletions or translocations were observed, unlike in Cas9 nuclease-edited cells[21][24] - The platform's modularity across Prime Editors, delivery, manufacturing, and regulatory aspects is expected to de-risk and accelerate the advancement of new programs[25][26] Clinical Pipeline This section details Prime Medicine's clinical pipeline, focusing on its liver, lung, immunology, and oncology franchises, and highlighting key programs and strategic collaborations Liver Franchise The liver franchise targets two of the largest genetic liver diseases, Wilson's Disease and Alpha-1 Antitrypsin Deficiency (AATD), using a universal, proprietary liver-targeted LNP delivery system. This modular approach is expected to accelerate development. The LNP has been well-tolerated in NHP studies. The Wilson's Disease program is advancing toward a H1 2026 IND/CTA filing, while the AATD program targets a mid-2026 filing. Preclinical data for both programs show efficient editing and restoration of protein function in humanized mouse models Liver Program Status and Timelines | Program | Targeted Mutations | Status | IND/CTA Filing Target | | :--- | :--- | :--- | :--- | | Wilson's Disease | H1069Q, R778L | IND-enabling | H1 2026 | | AATD | E342K (Pi*Z), D341H | Final lead optimization | Mid-2026 | - Both programs utilize a universal, proprietary GalNAc-targeted liver LNP, which has demonstrated >50% hepatocyte editing in NHPs and was well-tolerated at clinically relevant doses[33][39] - The LNP drug product is modular, with 6 out of 8 components being the same for liver programs, allowing for streamlined development[35] Wilson's Disease Program The Wilson's Disease program aims to correct mutations in the ATP7B gene to cure a disease affecting over 20,000 patients in the US and EU. Preclinical studies in humanized mouse models demonstrated efficient correction (>60%) of the two most prevalent mutations (H1069Q and R778L). This editing led to a ~75% reduction in liver copper and restoration of copper homeostasis. The company has initiated IND-enabling activities for a planned H1 2026 filing - The program targets a significant unmet need in Wilson's Disease, where correction of 20-30% of hepatocytes may be curative[45] - In vivo studies in humanized mouse models showed efficient correction of H1069Q and R778L mutations, with over 60% of hepatocytes corrected[47] - Correction of the H1069Q mutation resulted in a ~75% reduction in liver copper, ~80% decrease in urinary copper, and ~100% increase in fecal copper, indicating restored homeostasis[50] Alpha-1 Antitrypsin Deficiency (AATD) Program The AATD program targets the SERPINA1 gene to address both lung (loss-of-function) and liver (gain-of-function) disease affecting approximately 200,000 people in the US and EU. The goal is to correct the mutant Z-AAT protein to the healthy M-AAT form. In a humanized mouse model, Prime Editing successfully restored circulating AAT protein levels into the normal human range. The program is in the final stages of lead optimization, with an IND/CTA filing planned for mid-2026 - The objective is to normalize circulating AAT protein to healthy levels (~20uM or more) and reduce toxic Z-AAT protein in the liver, with 20-30% correction in hepatocytes potentially being curative[57][61] - In a fully humanized mouse model, Prime Editor treatment resulted in efficient correction of hepatocytes and restored serum M-AAT protein levels to the healthy human range[63][64] Lung Franchise The lung franchise is focused on developing a curative therapy for Cystic Fibrosis (CF), a disease affecting nearly 40,000 people in the U.S. The company is pursuing two parallel approaches: a 'Hotspot' strategy to correct the most common mutations and a 'PASSIGE' strategy for targeted gene insertion, which could potentially address nearly all CF patients. Supported by funding from the CF Foundation, the company has demonstrated phenotypic restoration of CFTR function in primary human bronchial epithelial cells for the G542X mutation and is advancing in vivo delivery efforts - Prime Editing approaches could potentially benefit over 93% of all people with CF, a disease for which there is no cure[70] - The company is developing two strategies: 'Hotspot' correction for common mutations and 'PASSIGE' for inserting a functional copy of the gene, aiming to address nearly all patients[74][75] - Prime Medicine has expanded its agreement with the CF Foundation, securing up to an additional $24 million in July 2025 to support CF program development[79] - For the G542X mutation, the company has shown phenotypic restoration of CFTR function in primary human bronchial epithelial (HBE) cells[80] Immunology and Oncology This franchise is anchored by a major strategic collaboration with Bristol Myers Squibb (BMS) to develop ex vivo CAR-T cell therapies for cancer and immunological diseases. The partnership leverages Prime's PASSIGE™ technology for one-step, non-viral gene-sized insertions. This approach aims to overcome key limitations of current CAR-T manufacturing by enabling high-efficiency (>80%) integration, precise on-target insertion, and safe, high-level multiplex editing without double-stranded breaks Bristol Myers Squibb (BMS) Collaboration Terms | Payment Type | Amount | | :--- | :--- | | Upfront | $110 million | | Preclinical Milestones | $185 million | | Development Milestones | $1.2 billion | | Commercial Milestones | >$2.1 billion | | Total Potential Milestones | >$3.5 billion | | Royalties | Royalties on net sales | - The collaboration aims to solve existing CAR-T limitations by using PASSIGE for precise, non-viral, single-step editing and integration, with the potential for no detectable off-target edits or translocations[87] - Prime Editing technology has demonstrated the ability to efficiently perform multiplex edits, achieving high editing rates for multiple gene targets (e.g., B2M, TRAC) simultaneously in CAR-T cells[89] Corporate Strategy and Position This section outlines Prime Medicine's corporate strategy, focusing on business development, intellectual property, and its overall investment proposition and financial outlook Business Development and Intellectual Property Prime Medicine's corporate strategy relies heavily on business development to accelerate its pipeline and secure financial resources, exemplified by its core partnerships with BMS for CAR-T and the CF Foundation for Cystic Fibrosis. The company holds an extensive and foundational intellectual property portfolio, with 6 issued U.S. patents and 12 ex-U.S. patents covering multiple configurations of Prime Editors, pegRNAs, and the PASSIGE system, ensuring broad protection for its technology - The company's partnering strategy focuses on leveraging its scientific leadership to form collaborations both within its core therapeutic areas (e.g., BMS) and to enable innovation in other areas[93][94] - Prime Medicine holds a strong IP position with 6 U.S. and 12 ex-U.S. issued patents[97] - The patent portfolio provides broad coverage for key technologies, including various Prime Editor and pegRNA configurations, dual flap editing, and the PASSIGE system for large gene insertions[99][102] Investment Summary Prime Medicine positions itself as the leader in Prime Editing, with the potential to address ~90% of genetic diseases. The company highlights its clinical proof of concept in CGD, a modular platform, and a strategically focused pipeline in large genetic diseases like Wilson's Disease and AATD. Key value drivers include its transformative partnership with BMS, funding from the CF Foundation, and a cash runway into the first half of 2026 - The company has achieved clinical proof of concept for Prime Editing with initial data from its CGD program[103] Key Pipeline and Financial Highlights | Item | Detail | | :--- | :--- | | Wilson's Disease | IND/CTA expected in H1 2026 | | AATD | IND/CTA expected in mid-2026 | | Partnerships | BMS collaboration for CAR-T; CF Foundation funding for CF | | Financials | Cash, equivalents, investments of $158.3M as of 3/31/2025 | | Cash Runway | Into H1 2026 | Appendix The appendix provides additional technical details on the Prime Editing platform. It includes a table outlining the capabilities of different Prime Editing approaches (Short Flap, Dual Flap, Long Flap, PASSIGE) for making edits of various sizes. It also elaborates on the PASSIGE technology, a one-step, non-viral method for inserting gene-sized DNA sequences, highlighting its current applications (CAR-T, CF) and future areas of opportunity (e.g., Hemophilia A, Fabry's disease) Prime Editing Approach Capabilities | Prime Editing Approach | Small Edits (bp swaps, small ins/del) | Mid-sized Edits (hotspot corrections) | Large Deletions (multi-kb) | Large Insertions (multi-kb) | | :--- | :--- | :--- | :--- | :--- | | Short Flap | +++ | + | | | | Dual Flap | +++ | ++ | | | | Long Flap | +++ | +++ | + | | | PASSIGE | | | ++ | +++ | - PASSIGE (Prime-Assisted Site-Specific Integrase Gene Editing) is a one-step, non-viral technology for inserting multi-kilobase gene sequences without double-stranded breaks[108] - Beyond current work in CAR-T and CF, PASSIGE presents opportunities for targeted whole gene replacement in diseases like Hemophilia A, Fanconi Anemia, and Phenylketonuria[109]