Question-and-Answer SessionAbsolutely. Maybe -- I know we were talking about this before, but you've recently become CEO of the company. And so maybe you could just kind of outline your strategic priorities, what you've been focused on, how you've been focusing your time and effort in this role now at the company?Allan ReineCEO & Director Yes. So as we think about -- as I think about strategic priorities and sort of capital allocation plan and how we really just build the best company that we can over the l ...

Vancouver, British Columbia – TheNewswire - September 8, 2025 – Western Star Resources Inc. (CSE: WSR; OTCQB: WSRIF) (“Western Star” or the “Company”) is pleased to announce that its common shares have been approved for trading on the OTCQB Venture Market (the “OTCQB”), a U.S. trading platform.The Company’s shares will commence trading on the OTCQB under the ticker symbol “WSRIF” effective Tuesday, September 9, 2025.The OTCQB is recognized as an established public market for international companies, provid ...

Summary of Prime Medicine FY Conference Call (September 08, 2025) Company Overview - **Company**: Prime Medicine (NasdaqGM:PRME) - **CEO**: Allan Reine - **Industry**: Biopharmaceuticals, specifically focusing on gene editing technologies Strategic Priorities - **Focus on Value Framework**: The company is prioritizing programs that can de-risk early, have high probabilities of success, address unmet medical needs, and present commercial opportunities [5][6] - **Key Programs**: - **Liver Programs**: Focus on Wilson's disease and Alpha-1 antitrypsin deficiency (AATD) due to high probability of success and effective delivery mechanisms [6][7] - **Cystic Fibrosis**: Progress is being made, funded by the Cystic Fibrosis Foundation, but delivery remains a challenge [7] - **Ex Vivo CAR-T Cell Therapy**: Collaboration with Bristol Myers Squibb is ongoing [8] Differentiation of Prime Editing Technology - **Safety and Precision**: Prime Editing offers a safer alternative to CRISPR-Cas9 by making single-stranded breaks, reducing off-target effects and indels [12][13] - **Broad Application Potential**: The technology can target various genetic diseases, including neurological disorders, which are currently underserved by existing gene editing technologies [9][10] Regulatory Environment - **Positive FDA Stance**: The FDA appears supportive of gene and cell therapies, potentially easing the path for Prime Medicine's products [15][16] - **Unique Approach**: The ability to return patients to wild-type protein without off-target effects may facilitate regulatory discussions [17] Clinical Programs and Data - **Chronic Granulomatous Disease**: Initial clinical data showed promising results, but the small patient population led to a decision not to invest further in this program [19][20][21] - **Upcoming IND Submissions**: Targeting IND submissions for Wilson's disease in the first half of 2026 and AATD in mid-2026 [28][29] Market Opportunities - **Wilson's Disease vs. AATD**: - Wilson's disease has a potential patient population of 10,000 to 11,000 in the U.S., with a focus on the 1069Q mutation [32][33] - AATD has a similar patient size but faces more competition [32][34] - **Global Market Considerations**: The prevalence of Wilson's disease mutations is higher in certain Asian populations, presenting additional opportunities [34] Preclinical Data and Efficacy - **High Editing Efficiency**: Both Wilson's disease and AATD programs have shown high editing efficiency and positive phenotypic data in preclinical studies [41][42] - **Clinical Trial Design**: Standard designs are anticipated for AATD, while Wilson's disease may involve novel biomarkers and imaging studies to assess efficacy [43][44] Collaboration and Financial Outlook - **Bristol Myers Squibb Collaboration**: The partnership includes $110 million upfront and $185 million in preclinical milestones, progressing well [57] - **Capital Management**: Recent capital raises extend cash runway into 2027, with a focus on reducing expenses and potential for further partnerships to enhance funding [59][60] Delivery Mechanisms - **Lipid Nanoparticle (LNP) Technology**: Effective for liver delivery, with ongoing evaluations of both internal and external delivery technologies for broader applications [49][50] - **Challenges in Cystic Fibrosis**: Addressing the difficulty of delivering therapies through mucus in the lungs remains a key focus [51][53] Conclusion - **Long-term Vision**: The company aims to create sustained value over the next five to ten years by leveraging its unique gene editing technology and addressing significant unmet medical needs in various genetic disorders [10][36]

Core Viewpoint - Prime Drink Group Corp. has terminated its rights offering and is moving forward with a non-brokered private placement to raise a maximum of $5,000,000 [1] Group 1: Private Placement Details - The private placement will offer units at a price of $5,000 per unit, each consisting of 62,500 common shares and 62,500 transferable share purchase warrants [2] - A maximum of 62,500,000 common shares will be issued at a deemed price of $0.08 per share, along with a maximum of 62,500,000 warrants [2] - Each warrant allows the holder to purchase a common share at $0.085 for two years from the issuance date [2] Group 2: Financial Aspects - The company will pay a cash finders' fee of 6% on the proceeds received from subscribers introduced by arm's-length finders [3] - The net proceeds from the unit offering will be used for business development and general working capital purposes [5] Group 3: Regulatory and Compliance - The units are offered through private placement exemptions from prospectus requirements under applicable securities laws, with resale restrictions including a hold period of four months and one day [4] - The offering is subject to final approval from the Canadian Securities Exchange and other regulatory approvals [4] Group 4: Company Overview - Prime Drink Group Corp. is based in Québec and aims to become a leading diversified holding company in the beverage, influencer media, and hospitality sectors [6]

Company Transition and Vision - The company announced a leadership transition with Allan Reine taking over as CEO on May 19 [2] - The company completed the final stage of pipeline prioritization, reducing the number of programs from 18 to 3 high-value programs focused on Wilson's disease, Alpha-1 Antitrypsin Deficiency, and cystic fibrosis [2] Collaboration and Future Strategy - The company is collaborating with BMS on ex vivo CAR-T therapies targeting immunology, hematology, and oncology [3] - The vision for the company is structured into short-term, medium-term, and long-term goals, indicating a strategic approach to future developments [3]

Summary of Prime Medicine Conference Call - September 02, 2025 Company Overview - **Company**: Prime Medicine (PRME) - **CEO**: Allan Reine - **Focus**: Gene editing technologies, specifically Prime Editing Key Points Pipeline and Strategic Focus - Transition to a focused pipeline with three high-value programs: Wilson's disease, Alpha-1 antitrypsin deficiency (AATD), and cystic fibrosis [4][5] - Previous pipeline had 18 programs, now streamlined for better capital allocation [4] - Collaboration with Bristol-Myers Squibb (BMS) for ex vivo CAR-T therapies, with $110 million upfront and $185 million in potential preclinical milestones [6] Clinical Development Timeline - Expecting Investigational New Drug (IND) application for Wilson's disease in the first half of 2026 and for AATD shortly thereafter [5][26] - Clinical data for both programs anticipated in 2027, marking a significant year for value creation [5] Prime Editing Technology - Prime Editing is described as the most versatile gene editing technology, capable of correcting various types of mutations beyond what CRISPR and base editing can achieve [6][54] - The technology allows for the insertion of multiple base pairs and correction of frameshift mutations, offering a broad range of applications [6] Clinical Data and Proof of Concept - Achieved proof of concept in chronic granulomatous disease (CGD) with rapid engraftment observed in treated patients [9][10] - Discontinued the CGD program but plans to engage with the FDA based on the strength of the data [12] Market Opportunities - **AATD**: Approximately 100,000 patients with the mutation in the U.S., with 10,000 to 15,000 diagnosed cases. Potential market size estimated at $20 billion to $40 billion [23][24] - **Wilson's Disease**: Targeting mutations prevalent in 30% to 50% of patients in the U.S. and higher in Asian populations. Global market opportunity estimated at $20 billion to $40 billion [30][33] Competitive Landscape - Limited competition in Wilson's disease, while AATD has multiple competitors. Prime Medicine aims to be a best-in-class therapy for AATD based on preclinical data [16][17] - Differentiation in the market is emphasized, particularly in the ability to return patients to wild-type protein levels [17][18] Future Directions and Partnerships - Potential for future business development deals, particularly in cell therapy and neurological diseases [57][58] - Ongoing arbitration with BEAM regarding the AATD program, with resolution expected in the first half of 2026 [28] Financial Position - Recent financing in August extended cash runway into 2027, with a pro forma cash position of approximately $260 million [60] Closing Remarks - The CEO expressed excitement about the company's technology and strategy, highlighting the transition from a lab-based company to one with human clinical data and upcoming programs [61] Additional Insights - The company is focused on leveraging its technology for unmet medical needs while ensuring commercial viability [54][56] - Emphasis on the importance of delivery mechanisms for gene editing therapies, particularly in challenging tissues like the lung for cystic fibrosis [48][50]

Core Viewpoint - Prime Drink Group Corp. has received an extension from the British Columbia Securities Commission to file its annual financial statements, now due by September 29, 2025, following a management cease trade order [1][2]. Group 1: Management Cease Trade Order (MCTO) - The MCTO was granted on July 30, 2025, preventing the CEO and CFO from trading the company's securities until the annual financial filings are submitted [1][2]. - Shareholders retain the ability to trade their securities despite the MCTO [2]. Group 2: Financial Filing Extension - The deadline for filing the annual financial statements for the period ended March 31, 2025, has been extended to September 29, 2025 [1]. - The company is actively working to meet this new deadline [2]. Group 3: Compliance and Reporting - The company will issue bi-weekly default status reports in the form of news releases to comply with alternative information guidelines under NP 12-203 until the annual financial filings are submitted [3].

Core Viewpoint - Prime Medicine, Inc. reported a quarterly loss of $0.41 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.36, representing an earnings surprise of -13.89% [1][2] Financial Performance - The company posted revenues of $1.12 million for the quarter ended June 2025, missing the Zacks Consensus Estimate by 59.6%, compared to zero revenues a year ago [2] - Over the last four quarters, Prime Medicine has surpassed consensus EPS estimates only once [2] Stock Performance - Prime Medicine shares have increased by approximately 39.4% since the beginning of the year, outperforming the S&P 500's gain of 7.9% [3] Future Outlook - The current consensus EPS estimate for the upcoming quarter is -$0.29 on revenues of $2.59 million, and for the current fiscal year, it is -$1.30 on revenues of $7.74 million [7] - The estimate revisions trend for Prime Medicine was favorable ahead of the earnings release, resulting in a Zacks Rank 2 (Buy) for the stock, indicating expected outperformance in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Prime Medicine belongs, is currently in the top 41% of over 250 Zacks industries, suggesting a favorable outlook for stocks in this sector [8]

[PART I - FINANCIAL INFORMATION](index=5&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements (unaudited)](index=5&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This section presents the unaudited condensed consolidated financial statements for Q2 and H1 2025, including balance sheets, operations, cash flows, and detailed notes [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of June 30, 2025, total assets decreased to **$279.0 million** while total liabilities increased to **$218.1 million**, driven by operating lease liabilities Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $53,804 | $182,476 | | Total current assets | $121,287 | $211,886 | | Total assets | $279,009 | $297,508 | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $34,109 | $37,961 | | Operating lease liability, net of current | $112,478 | $37,180 | | Total liabilities | $218,149 | $144,359 | | Total stockholders' equity | $60,860 | $153,149 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Q2 2025 saw **$1.1 million** in revenue and a **$52.6 million** net loss, while H1 2025 net loss was **$104.5 million** Statement of Operations Summary (in thousands, except per share data) | Metric | Q2 2025 | Q2 2024 | H1 2025 | H1 2024 | | :--- | :--- | :--- | :--- | :--- | | Total revenue | $1,115 | $0 | $2,569 | $591 | | Research and development | $41,375 | $43,071 | $81,937 | $80,845 | | General and administrative | $13,117 | $12,601 | $26,401 | $23,759 | | Loss from operations | $(53,377) | $(55,672) | $(105,769) | $(104,013) | | Net loss | $(52,591) | $(55,327) | $(104,481) | $(101,088) | | Net loss per share | $(0.41) | $(0.46) | $(0.81) | $(0.90) | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) H1 2025 net cash used in operating activities was **$90.3 million**, with financing activities providing **$6.2 million**, ending the period with **$67.5 million** in cash Cash Flow Summary for the Six Months Ended June 30 (in thousands) | Cash Flow Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(90,269) | $(113,198) | | Net cash used in investing activities | $(44,971) | $(30,138) | | Net cash provided by financing activities | $6,197 | $157,362 | | **Net change in cash, cash equivalents, and restricted cash** | **$(129,043)** | **$14,026** | | Cash, cash equivalents, and restricted cash at end of period | $67,495 | $69,096 | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes detail liquidity, accounting policies, and key agreements, including a **$138.2 million** stock offering, stock option repricing, and ongoing arbitration with Beam Therapeutics - In August 2025, the company raised approximately **$138.2 million** in net proceeds from a common stock offering, which is expected to be sufficient to fund operations for at least the next twelve months[34](index=34&type=chunk)[35](index=35&type=chunk) - On August 1, 2025, the company repriced certain outstanding employee and director stock options with exercise prices above **$4.04** down to **$4.04** per share to improve retention and incentive value[80](index=80&type=chunk)[81](index=81&type=chunk) - The company is in an arbitration proceeding with Beam Therapeutics, Inc regarding a dispute over the development of a treatment for alpha-1 antitrypsin deficiency (AATD)[89](index=89&type=chunk)[141](index=141&type=chunk) - In July 2025, the company entered into an agreement with the Cystic Fibrosis Foundation (CFF) for up to **$24 million** in additional funding to accelerate the development of Prime Editors for cystic fibrosis[87](index=87&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=24&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the strategic shift to the in vivo liver franchise, analyzes Q2 and H1 2025 financial results, and highlights a **$138.2 million** financing extending the cash runway into 2027 [Overview and Business Update](index=27&type=section&id=Overview%20and%20Business%20Update) The company strategically refocused on its in vivo liver franchise (Wilson's Disease, AATD) with 2026 IND/CTA filings, while continuing CF and CAR-T programs and seeking partners for PM359 - Strategic focus has shifted to the in vivo liver franchise, targeting Wilson's Disease and AATD, with IND/CTA filings anticipated in the first half and middle of 2026, respectively[94](index=94&type=chunk) - The company will continue its Cystic Fibrosis program, supported by up to **$24 million** in additional funding from the Cystic Fibrosis Foundation, and its CAR-T collaboration with Bristol-Myers Squibb[95](index=95&type=chunk)[96](index=96&type=chunk) - Initial data from the Phase 1/2 trial of PM359 for CGD showed high levels of dihydrorhodamine positivity, considered potentially curative; the company is now seeking partners for this program following its strategic shift[97](index=97&type=chunk) [Results of Operations](index=29&type=section&id=Results%20of%20Operations) Q2 2025 R&D expenses decreased by **$1.7 million** due to program deprioritization, while H1 2025 G&A expenses increased by **$2.6 million** from severance and legal fees R&D Expense Comparison - Q2 (in thousands) | Category | Q2 2025 | Q2 2024 | Change | | :--- | :--- | :--- | :--- | | Personnel expenses | $14,448 | $16,198 | $(1,750) | | Facility related | $13,765 | $11,302 | $2,463 | | Research costs | $8,116 | $11,390 | $(3,274) | | **Total R&D expenses** | **$41,375** | **$43,071** | **$(1,696)** | G&A Expense Comparison - H1 (in thousands) | Category | H1 2025 | H1 2024 | Change | | :--- | :--- | :--- | :--- | | Personnel expenses | $14,238 | $12,840 | $1,398 | | Professional and consultant fees | $7,228 | $5,931 | $1,297 | | **Total G&A expenses** | **$26,401** | **$23,759** | **$2,642** | - The decrease in Q2 R&D spending was driven by a **$3.3 million** reduction in research costs and a **$1.1 million** drop in clinical expenses due to the deprioritization of the CGD program[107](index=107&type=chunk) - The increase in H1 G&A expenses was primarily due to a **$1.4 million** increase in personnel costs related to one-time severance payments from the workforce reduction and a **$1.3 million** increase in corporate legal fees[112](index=112&type=chunk)[116](index=116&type=chunk) [Liquidity and Capital Resources](index=34&type=section&id=Liquidity%20and%20Capital%20Resources) As of June 30, 2025, the company held **$101.8 million** in cash and investments, supplemented by a **$138.2 million** August 2025 stock offering, extending its cash runway into 2027 - As of June 30, 2025, the company held **$101.8 million** in cash, cash equivalents, and investments[117](index=117&type=chunk) - An August 2025 stock offering generated approximately **$138.2 million** in net proceeds, extending the company's cash runway into 2027[118](index=118&type=chunk)[126](index=126&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=32&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity on its **$115.4 million** investment portfolio, though a 10% rate change is not expected to be material - The company is exposed to interest rate risk on its **$115.4 million** portfolio of cash, cash equivalents, investments, and restricted cash[135](index=135&type=chunk) - Management does not believe a 10% change in interest rates would materially affect the fair market value of its investments due to their short-term nature[135](index=135&type=chunk) [Item 4. Controls and Procedures](index=33&type=section&id=Item%204.%20Controls%20and%20Procedures) As of June 30, 2025, the company's disclosure controls and procedures were effective, with no material changes to internal control over financial reporting during Q2 2025 - The company's disclosure controls and procedures were deemed effective as of the end of the period covered by this report (June 30, 2025)[138](index=138&type=chunk) - No changes occurred during the quarter that have materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[139](index=139&type=chunk) [PART II - OTHER INFORMATION](index=34&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=34&type=section&id=Item%201.%20Legal%20Proceedings) The company is in arbitration with Beam Therapeutics over alleged breach of a collaboration agreement regarding the AATD program, with Beam seeking damages and program transfer - The company is in a consolidated arbitration proceeding with Beam Therapeutics regarding the development of a treatment for AATD[141](index=141&type=chunk) - Beam alleges breach of contract and seeks declaratory, injunctive, and monetary relief, which could include forcing the company to cease work on its AATD program and transfer it to Beam[141](index=141&type=chunk) [Item 1A. Risk Factors](index=34&type=page&id=Item%201A.%20Risk%20Factors) Updated risk factors include healthcare reform, U.S. tax/trade policy changes, challenges in retaining key personnel, collaborator disputes, and operational risks from the May 2025 restructuring - Healthcare reform, including the Inflation Reduction Act of 2022 (IRA), could increase costs, add downward pressure on drug prices, and adversely affect profitability[143](index=143&type=chunk)[147](index=147&type=chunk) - The company's ability to retain key employees is a significant risk, exacerbated by a declining stock price that has left many stock options "underwater"; a recent option repricing was implemented to address this[158](index=158&type=chunk)[160](index=160&type=chunk) - The ongoing arbitration with Beam Therapeutics is highlighted as a material risk, as an adverse outcome could result in monetary damages and the loss of the company's AATD program[163](index=163&type=chunk) - The May 2025 strategic restructuring and workforce reduction may not achieve anticipated cost savings and could disrupt operations, reduce morale, and lead to further attrition[164](index=164&type=chunk)[165](index=165&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=39&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities occurred during the three months ended June 30, 2025 - There were no unregistered sales of equity securities in the three months ended June 30, 2025[167](index=167&type=chunk) [Item 5. Other Information](index=39&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted, modified, or terminated Rule 10b5-1 trading plans during the three months ended June 30, 2025 - No directors or officers adopted, modified, or terminated a Rule 10b5-1 trading plan during the quarter[171](index=171&type=chunk) [Item 6. Exhibits](index=40&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Quarterly Report on Form 10-Q, including officer certifications and various agreements

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](index=2&type=section&id=Forward%20Looking%20Statements) 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](index=2&type=chunk) - 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](index=2&type=chunk) [Company Mission and Strategic Roadmap](index=3&type=section&id=Company%20Mission%20and%20Strategic%20Roadmap) 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](index=4&type=chunk) 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](index=9&type=chunk) 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](index=6&type=section&id=Platform%20Capabilities%20and%20Clinical%20Proof%20of%20Concept) 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](index=11&type=chunk)[12](index=12&type=chunk) 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](index=8&type=section&id=Differentiated%20Safety%20Profile%20and%20Platform%20Modularity) 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](index=18&type=chunk)[19](index=19&type=chunk)[20](index=20&type=chunk) - 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](index=21&type=chunk)[24](index=24&type=chunk) - 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](index=25&type=chunk)[26](index=26&type=chunk) 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](index=11&type=section&id=Liver%20Franchise) 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](index=33&type=chunk)[39](index=39&type=chunk) - The LNP drug product is modular, with **6 out of 8 components** being the same for liver programs, allowing for streamlined development[35](index=35&type=chunk) [Wilson's Disease Program](index=15&type=section&id=Wilson%27s%20Disease) 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](index=45&type=chunk) - In vivo studies in humanized mouse models showed efficient correction of H1069Q and R778L mutations, with **over 60% of hepatocytes** corrected[47](index=47&type=chunk) - 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](index=50&type=chunk) [Alpha-1 Antitrypsin Deficiency (AATD) Program](index=19&type=section&id=Alpha-1%20Antitrypsin%20Deficiency%20%28AATD%29) 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](index=57&type=chunk)[61](index=61&type=chunk) - 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](index=63&type=chunk)[64](index=64&type=chunk) [Lung Franchise](index=23&type=section&id=Lung%20Franchise) 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](index=70&type=chunk) - 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](index=74&type=chunk)[75](index=75&type=chunk) - 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](index=79&type=chunk) - For the G542X mutation, the company has shown phenotypic restoration of CFTR function in primary human bronchial epithelial (HBE) cells[80](index=80&type=chunk) [Immunology and Oncology](index=27&type=section&id=Immunology%20and%20Oncology) 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](index=87&type=chunk) - 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](index=89&type=chunk) 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](index=32&type=section&id=Business%20Development%20and%20Intellectual%20Property) 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](index=93&type=chunk)[94](index=94&type=chunk) - Prime Medicine holds a strong IP position with **6 U.S. and 12 ex-U.S. issued patents**[97](index=97&type=chunk) - 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](index=99&type=chunk)[102](index=102&type=chunk) [Investment Summary](index=34&type=section&id=Investment%20Summary) 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](index=103&type=chunk) 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](index=108&type=chunk) - 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](index=109&type=chunk)