Group 1 - Precision BioSciences reported a quarterly loss of $2.21 per share, significantly worse than the Zacks Consensus Estimate of a loss of $0.43, representing an earnings surprise of -413.95% [1] - The company posted revenues of $0.03 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 99.71%, compared to revenues of $17.58 million a year ago [2] - The stock has increased approximately 29.9% since the beginning of the year, outperforming the S&P 500's gain of 0.2% [3] Group 2 - The earnings outlook for Precision BioSciences is currently unfavorable, with a Zacks Rank of 4 (Sell), indicating expected underperformance in the near future [6] - The current consensus EPS estimate for the upcoming quarter is -$0.08 on revenues of $13.7 million, and -$1.17 on revenues of $45.6 million for the current fiscal year [7] - The Medical - Biomedical and Genetics industry is ranked in the top 28% of over 250 Zacks industries, suggesting a favorable industry outlook [8]

Precision BioSciences (DTIL) Conference Call Summary Company Overview - **Company**: Precision BioSciences - **Focus**: Gene editing therapies, particularly for Duchenne muscular dystrophy (DMD) and chronic hepatitis B (HBV) Key Points from the Conference Call Industry and Market Context - **Duchenne Muscular Dystrophy (DMD)**: A genetic disorder leading to progressive muscle degeneration, with approximately 300,000 to 400,000 patients globally and 15,000 new cases in the U.S. annually [9] - **Current Treatment Landscape**: Existing therapies, including microdystrophins and exon skipping, have not achieved significant long-term muscle functional improvement [7][43] Core Program Updates - **PBGene DMD**: - A clinical-stage candidate aimed at providing durable muscle functional improvement for DMD patients, focusing on correcting mutations in the dystrophin gene [5][6] - The program is designed to address the highest unmet needs in DMD, with a unique mechanism that allows for the production of a near full-length dystrophin protein [20][31] - Preclinical data shows significant improvements in muscle force output in treated mice, maintaining improvements up to nine months post-treatment [22][23] Safety and Efficacy - **Safety Profile**: The use of lower doses of AAV (adeno-associated virus) is expected to enhance safety, reducing the risk associated with high doses [35][49] - **Durability of Treatment**: The ability to edit satellite cells is crucial for long-term muscle function improvement, with evidence of increased dystrophin protein expression over time [25][28][99] Regulatory Pathway - **FDA Interactions**: Precision BioSciences has had positive discussions with the FDA regarding their clinical trial design and biomarker linkage to functional improvement [59][102] - **Clinical Trial Timeline**: Targeting to file a CTA or IND by late 2025, with clinical trials expected to commence in 2026 [61][66] Financial and Operational Updates - **Resource Allocation**: The company is prioritizing its resources towards the HBV and DMD programs, pausing the PBGene 3243 mitochondrial DNA elimination program for fiscal reasons [62][64] - **Cash Runway**: The company has sufficient cash runway into the second half of 2026 to meet Phase 1 clinical requirements [68] Additional Insights - **Patient Perspective**: The potential for improved durability and better dystrophin expression is seen as a significant advancement over current therapies, which have struggled to demonstrate clinical efficacy [46][53] - **Commercial Considerations**: Screening for neutralizing antibodies will be critical, as many patients may have previously received AAV therapies, impacting eligibility for new treatments [80][83] Conclusion - Precision BioSciences is positioned to make significant advancements in the treatment of DMD and HBV, with promising preclinical data and a clear regulatory pathway. The focus on safety, efficacy, and patient needs underscores the company's commitment to addressing high unmet medical needs in these areas.

[First Quarter 2025 Financial Results and Business Update](index=1&type=section&id=First%20Quarter%202025%20Financial%20Results%20and%20Business%20Update) Precision BioSciences reported strong Q1 2025 momentum with significant clinical data, regulatory approvals, and accelerated program development [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Michael Amoroso highlighted strong Q1 2025 momentum, significant clinical data generation, and accelerated program development - ARCUS in vivo gene insertion validated clinically with a **complete response** in an infant with OTC-deficiency[3](index=3&type=chunk) - Phase 1 ELIMINATE-B trial for chronic Hepatitis B (PBGENE-HBV) progressing, with **encouraging safety data** after repeat dosing presented at EASL Congress[3](index=3&type=chunk) - U.S. IND approval and Fast Track Designation received for PBGENE-HBV, underscoring its potential for a curative treatment[3](index=3&type=chunk) - PBGENE-DMD program accelerated, targeting IND/CTA in 2025 with clinical data in 2026, based on preclinical proof of protein expression and improved muscle function[3](index=3&type=chunk)[4](index=4&type=chunk) [First Quarter 2025 Business Highlights](index=1&type=section&id=First%20Quarter%202025%20Business%20Highlights) Q1 2025 achievements include new clinical data, initial safety results, regulatory clearances, program acceleration, and extended cash runway - New clinical data announced for two programs, validating safety and efficacy of ARCUS in vivo gene editing[4](index=4&type=chunk) - Initial safety data from Phase 1 ELIMINATE-B trial (PBGENE-HBV) presented at EASL, with ongoing clinical updates expected throughout 2025[4](index=4&type=chunk) - Regulatory clearance of IND from U.S. FDA to expand ELIMINATE-B trial and CTA approved by MHRA for UK expansion; PBGENE-HBV granted U.S. FDA Fast Track Designation[4](index=4&type=chunk) - PBGENE-DMD program accelerated to be a first-in-class in vivo gene editing approach for Duchenne's Muscular Dystrophy, targeting IND/CTA in 2025 and clinical data in 2026[4](index=4&type=chunk) - Expected cash runway into **second half of 2026**, enabling data readouts from lead wholly-owned programs (PBGENE-HBV and PBGENE-DMD)[4](index=4&type=chunk) [Pipeline Update](index=2&type=section&id=Pipeline%20Update) Precision BioSciences is advancing its wholly-owned and partnered programs, achieving key clinical and preclinical milestones [Wholly Owned Portfolio](index=2&type=section&id=Wholly%20Owned%20Portfolio) The company is prioritizing PBGENE-HBV and PBGENE-DMD, showing promising clinical and preclinical data, while pausing PBGENE-3243 [PBGENE-HBV (Viral Elimination Program)](index=2&type=section&id=PBGENE-HBV%20(Viral%20Elimination%20Program)) PBGENE-HBV demonstrated initial safety and HBsAg reduction, receiving U.S. IND and Fast Track, and U.K. CTA clearances - PBGENE-HBV is the first and only gene editing program in clinic designed to eliminate cccDNA and inactivate integrated HBV DNA for chronic Hepatitis B[5](index=5&type=chunk) - Initial results from cohort 1 showed PBGENE-HBV was safe and well tolerated, with **substantial reduction in Hepatitis B surface antigen (HBsAg)** in two of three participants at the lowest dose[6](index=6&type=chunk) - Received U.S. FDA clearance for Phase 1 trials and Fast Track designation in March/April 2025; U.K. MHRA also cleared for Phase 1 trial, making it the fifth country[7](index=7&type=chunk) - Initial safety data presented at EASL Congress on May 8, 2025, supported pre-planned repeat dosing and dose escalation[8](index=8&type=chunk) [PBGENE-DMD (Muscle Targeted Excision Program)](index=2&type=section&id=PBGENE-DMD%20(Muscle%20Targeted%20Excision%20Program)) PBGENE-DMD showed significant functional improvement in preclinical models and is prioritized for 2025 IND/CTA filing - PBGENE-DMD addresses over **60% of DMD patients** by excising exons 45-55 to restore a near-full length functional dystrophin protein[9](index=9&type=chunk) - Preclinical data presented at MDA and ASGCT demonstrated **significant, durable functional improvement** and restoration of dystrophin protein across multiple muscles, including cardiac tissue, in a humanized DMD mouse model[10](index=10&type=chunk)[11](index=11&type=chunk) - The program is prioritized as the second wholly-owned clinical program, targeting IND/CTA filing in 2025 and clinical data in 2026[12](index=12&type=chunk) [PBGENE-3243 (Mutant Mitochondrial DNA Elimination Program)](index=3&type=section&id=PBGENE-3243%20(Mutant%20Mitochondrial%20DNA%20Elimination%20Program)) PBGENE-3243 showed preclinical efficacy in mutant mtDNA elimination but is paused to focus on lead programs - PBGENE-3243 is designed to specifically target and eliminate mutant m.3243G mitochondrial DNA, addressing the root cause of m.3243-associated mitochondrial disease[13](index=13&type=chunk) - New preclinical data at ASGCT showed an ARCUS nuclease can eliminate mutant mitochondrial DNA and achieve therapeutically meaningful heteroplasmy shifts in vivo[14](index=14&type=chunk) - Development of PBGENE-3243 is paused to accelerate PBGENE-DMD, with future development to be staged after PBGENE-HBV Phase 1 completion and PBGENE-DMD reaching the clinic[15](index=15&type=chunk) [Partnered Programs](index=3&type=section&id=Partnered%20Programs) Partnered programs iECURE-OTC and PBGENE-NVS are progressing, with iECURE-OTC showing a complete clinical response [iECURE-OTC (Gene Insertion Program)](index=3&type=section&id=iECURE-OTC%20(Gene%20Insertion%20Program)) iECURE-OTC reported a complete clinical response in an OTC-deficient infant, with full enrollment expected in 2025 - iECURE-OTC (ECUR-506) is an ARCUS-mediated in vivo gene editing program for neonatal onset OTC deficiency, currently in a Phase 1/2 trial (OTC-HOPE)[16](index=16&type=chunk) - Clinical efficacy and safety data from the first patient showed a **complete clinical response** from three months post-exposure to six months, with the patient now over one year old and eating age-appropriate protein levels[16](index=16&type=chunk) - The OTC-HOPE study is ongoing in multiple countries, with enrollment expected to complete in 2025 and complete data anticipated in the first half of 2026[17](index=17&type=chunk) [PBGENE-NVS (Gene Insertion Program)](index=3&type=section&id=PBGENE-NVS%20(Gene%20Insertion%20Program)) PBGENE-NVS, in collaboration with Novartis, aims for an in vivo gene insertion therapy for hemoglobinopathies - Precision continues to advance its gene editing program with Novartis (PBGENE-NVS) for hemoglobinopathies such as sickle cell disease and beta thalassemia[18](index=18&type=chunk) - The program aims to insert a therapeutic transgene in vivo as a potential **one-time transformative treatment**, overcoming access disparities of ex vivo approaches[18](index=18&type=chunk) [First Quarter 2025 Financial Performance](index=4&type=section&id=First%20Quarter%202025%20Financial%20Performance) Precision BioSciences reported a net loss in Q1 2025 due to decreased revenue, with R&D and G&A expenses remaining stable [Cash, Cash Equivalents, and Restricted Cash](index=4&type=section&id=Cash,%20Cash%20Equivalents,%20and%20Restricted%20Cash) Cash, cash equivalents, and restricted cash totaled approximately **$100 million**, extending the cash runway into H2 2026 Cash Position | Metric | March 31, 2025 | December 31, 2024 | | :-------------------------------- | :------------- | :---------------- | | Cash, cash equivalents, and restricted cash | $99,789 thousand | $108,468 thousand | - Company expects cash runway into the **second half of 2026**, enabling data readouts from PBGENE-HBV and PBGENE-DMD through Phase 1[19](index=19&type=chunk) [Revenues](index=4&type=section&id=Revenues) Total revenues significantly decreased to **less than $0.1 million** in Q1 2025 due to concluded collaboration agreements Revenue Comparison (Q1 2025 vs Q1 2024) | Metric | Q1 2025 | Q1 2024 | Change | | :------- | :------ | :------ | :----- | | Revenue | < $0.1M | $17.6M | -$17.6M | - Decrease due to revenue recognized from TG Therapeutics and Caribou Biosciences agreements in Q1 2024, decrease in Prevail agreement revenue (concluded April 2024), and decrease in Novartis Agreement revenue as preclinical work nears completion[20](index=20&type=chunk) [Research and Development Expenses](index=4&type=section&id=Research%20and%20Development%20Expenses) R&D expenses slightly increased to **$13.6 million** in Q1 2025, driven by the advancement of the PBGENE-DMD program R&D Expenses Comparison (Q1 2025 vs Q1 2024) | Metric | Q1 2025 | Q1 2024 | Change | | :------------------------ | :-------- | :-------- | :----- | | Research and development | $13.6M | $13.3M | +$0.3M | - Increase primarily due to increased direct expense for PBGENE-DMD as the program advances towards the clinic[21](index=21&type=chunk) [General and Administrative Expenses](index=4&type=section&id=General%20and%20Administrative%20Expenses) G&A expenses rose slightly to **$8.6 million** in Q1 2025, primarily due to higher employee-related costs G&A Expenses Comparison (Q1 2025 vs Q1 2024) | Metric | Q1 2025 | Q1 2024 | Change | | :-------------------------- | :-------- | :-------- | :----- | | General and administrative | $8.6M | $8.4M | +$0.2M | - Increase primarily due to employee-related costs, partially offset by decreases in depreciation, amortization, taxes, and insurance[22](index=22&type=chunk) [Net Loss](index=4&type=section&id=Net%20Loss) The company reported a net loss of **$(20.6) million**, or **$(2.21) per share**, in Q1 2025 Net (Loss) Income and EPS Comparison (Q1 2025 vs Q1 2024) | Metric | Q1 2025 | Q1 2024 | | :---------------------- | :-------- | :-------- | | Net (loss) income | $(20.6)M | $8.6M | | Net (loss) income per share (Basic) | $(2.21) | $1.70 | | Net (loss) income per share (Diluted) | $(2.21) | $1.70 | [Company Information](index=4&type=section&id=Company%20Information) Precision BioSciences is a clinical-stage gene editing company leveraging its ARCUS® platform for in vivo therapies [Company Profile](index=4&type=section&id=Company%20Profile) Precision BioSciences is a clinical-stage gene editing company developing in vivo therapies for high unmet medical needs - Precision BioSciences is a clinical stage gene editing company utilizing its proprietary ARCUS® genome editing platform[24](index=24&type=chunk) - Lead programs are PBGENE-HBV for chronic Hepatitis B and PBGENE-DMD for Duchenne muscular dystrophy, targeting diseases with high unmet need[24](index=24&type=chunk) [ARCUS® Genome Editing Platform](index=4&type=section&id=ARCUS%C2%AE%20Genome%20Editing%20Platform) The ARCUS® platform is a unique genome editing technology enabling gene insertion, elimination, and excision capabilities - ARCUS® platform differs from other technologies in its cutting mechanism, smaller size, and simpler structure[24](index=24&type=chunk) - Capabilities include gene insertion (adding function), elimination (removing viral DNA), and excision (removing defective gene portions)[25](index=25&type=chunk) [Financial Statements](index=7&type=section&id=Financial%20Statements) Financial statements detail Q1 2025 performance, including a significant revenue decrease, operating loss, and balance sheet changes [Statements of Operations](index=7&type=section&id=Statements%20of%20Operations) Statements of Operations show a Q1 2025 net loss of **$(20.6) million** due to decreased revenue, with stable expenses Statements of Operations (In thousands, except share and per share amounts) | Metric | For the Three Months Ended March 31, 2025 | For the Three Months Ended March 31, 2024 | | :-------------------------------------- | :---------------------------------------- | :---------------------------------------- | | Revenue | $29 | $17,584 | | Research and development | $13,588 | $13,343 | | General and administrative | $8,553 | $8,428 | | Total operating expenses | $22,141 | $21,771 | | Operating loss | $(22,112) | $(4,187) | | Total other income | $1,547 | $12,775 | | Net (loss) income | $(20,565) | $8,588 | | Net (loss) income per share (Basic) | $(2.21) | $1.70 | | Net (loss) income per share (Diluted) | $(2.21) | $1.70 | | Weighted-average shares outstanding (Basic) | 9,292,066 | 5,060,978 | | Weighted-average shares outstanding (Diluted) | 9,292,066 | 5,063,406 | [Balance Sheets Data](index=8&type=section&id=Balance%20Sheets%20Data) Balance sheets data indicates a decrease in cash, total assets, and liabilities as of March 31, 2025 Balance Sheets Data (In thousands, except share amounts) | Metric | March 31, 2025 | December 31, 2024 | | :-------------------------------- | :------------- | :---------------- | | Cash, cash equivalents, and restricted cash | $99,789 | $108,468 | | Working capital | $69,710 | $80,009 | | Total assets | $124,411 | $136,388 | | Total liabilities | $75,074 | $79,995 | | Total stockholders' equity | $49,337 | $56,393 | | Common stock outstanding | 10,548,852 | 8,202,715 | [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) This section outlines future expectations, beliefs, and assumptions, along with inherent risks and uncertainties that may impact actual results

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20%28unaudited%29) Precision BioSciences reported a significant Q1 2025 revenue decrease to $29 thousand, a net loss of $20.6 million, and reduced total assets Condensed Balance Sheet Data (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $77,223 | $85,899 | | Restricted cash | $22,566 | $22,569 | | Total Assets | $124,411 | $136,388 | | Total Liabilities | $75,074 | $79,995 | | Total Stockholders' Equity | $49,337 | $56,393 | Condensed Statement of Operations (in thousands, except per share data) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Revenue | $29 | $17,584 | | Total operating expenses | $22,141 | $21,771 | | Operating loss | $(22,112) | $(4,187) | | Net (loss) income | $(20,565) | $8,588 | | Net (loss) income per share (Basic & Diluted) | $(2.21) | $1.70 | Condensed Statement of Cash Flows (in thousands) | Cash Flow Activity | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(19,052) | $(18,981) | | Net cash used in investing activities | $(314) | $(26) | | Net cash provided by financing activities | $10,687 | $40,095 | | Net (decrease) increase in cash | $(8,679) | $(21,088) | [Notes to Condensed Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Financial%20Statements) Notes detail the company's strategic shift to in vivo gene editing, key collaborations, and financial specifics like loan and warrant liabilities - The company has strategically shifted to **focus exclusively on developing in vivo gene editing therapies**, with its former CAR T programs now accounted for as **discontinued operations**[30](index=30&type=chunk)[31](index=31&type=chunk) - Revenue from the Novartis collaboration was **less than $0.1 million** in Q1 2025, down from **$4.5 million** in Q1 2024. Deferred revenue related to this agreement was **$26.2 million** as of March 31, 2025[54](index=54&type=chunk) - The company has a **$22.5 million** term loan with Banc of California, with a stated interest rate of **6.00%** as of March 31, 2025[38](index=38&type=chunk)[39](index=39&type=chunk) - R&D expenses are broken down by program, with PBGENE-DMD and PBGENE-3243 seeing increased spending, while PBGENE-HBV spending decreased as it moved into the clinic[81](index=81&type=chunk) - Warrants from the March 2024 public offering are **classified as a liability**, valued at **$3.6 million** as of March 31, 2025, with changes in fair value recorded in the statement of operations[82](index=82&type=chunk)[84](index=84&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=22&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the strategic focus on ARCUS gene editing, program updates for PBGENE-HBV and PBGENE-DMD, and financial outlook - The company is a clinical-stage gene editing company focused on developing in vivo therapies for genetic and infectious diseases using its proprietary ARCUS platform[88](index=88&type=chunk) - PBGENE-HBV for chronic Hepatitis B is in a global first-in-human clinical trial. Initial data from the first cohort was safe and well-tolerated, with substantial HBsAg reduction. The FDA has granted **Fast Track designation**[90](index=90&type=chunk)[91](index=91&type=chunk)[92](index=92&type=chunk) - The company is prioritizing and accelerating the PBGENE-DMD program for Duchenne muscular dystrophy, targeting an IND and/or CTA filing in 2025 with clinical data expected in 2026[97](index=97&type=chunk) - Development of PBGENE-3243 for mitochondrial disease is being paused to accelerate PBGENE-DMD and conserve resources[100](index=100&type=chunk) Results of Operations Comparison (in thousands) | Line Item | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Revenue | $29 | $17,584 | $(17,555) | | Research and development | $13,588 | $13,343 | $245 | | General and administrative | $8,553 | $8,428 | $125 | | Net (loss) income | $(20,565) | $8,588 | $(29,153) | - The company believes its existing cash and cash equivalents of **$99.8 million** will be **sufficient to fund operating expenses and capital expenditure requirements into the second half of 2026**[155](index=155&type=chunk) [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 $99.8 million cash, with no material impact expected from fluctuations - The company's main market risk is interest rate sensitivity on its cash, cash equivalents, and restricted cash, which totaled **$99.8 million** at March 31, 2025[165](index=165&type=chunk) - A hypothetical 10% change in interest rates is not expected to have a material impact on the company's financial condition[165](index=165&type=chunk) [Controls and Procedures](index=32&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls were effective as of March 31, 2025, with no material changes to internal controls - The CEO and CFO concluded that the company's disclosure controls and procedures were **effective as of March 31, 2025**[167](index=167&type=chunk) - No material changes were made to the internal control over financial reporting during the three months ended March 31, 2025[168](index=168&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=33&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings - As of the report date, the company is **not involved in any material legal proceedings**[170](index=170&type=chunk) [Risk Factors](index=33&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including historical losses, funding needs, unproven technology, regulatory complexities, and capital raising limitations - The company has a history of significant operating losses (**$503.0 million** accumulated deficit as of March 31, 2025) and expects to incur losses for the foreseeable future, requiring substantial additional funding[172](index=172&type=chunk)[176](index=176&type=chunk) - The ARCUS gene editing platform is a novel technology, making it difficult to predict the time, cost, and success of product development. The company has not yet been able to assess the safety and efficacy of most of its product candidates in humans[193](index=193&type=chunk) - The regulatory landscape for gene editing therapies is rigorous, complex, and subject to change, which could result in delays, termination of development, or unexpected costs[215](index=215&type=chunk) - The company relies on third parties for collaborations (e.g., Novartis), conducting clinical trials (CROs), and manufacturing (CMOs), and the failure of these parties to perform could substantially harm the business[355](index=355&type=chunk)[362](index=362&type=chunk)[368](index=368&type=chunk) - As of the filing date, the company is subject to the "Baby Shelf Rule," which limits the amount of funds it can raise through its Form S-3 registration statement to **one-third of its public float** in any 12-month period[179](index=179&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=83&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) On January 6, 2025, the company issued **220,712** unregistered common shares to TG Subsidiary for a **$2.5 million** deferred cash payment - On January 6, 2025, the company issued **220,712 shares** of common stock to TG Subsidiary in exchange for a **$2.5 million** deferred cash payment related to their license agreement[439](index=439&type=chunk) - The issuance was an unregistered sale, relying on the **Section 4(a)(2) exemption** under the Securities Act[439](index=439&type=chunk) [Other Information](index=83&type=section&id=Item%205.%20Other%20Information) Two executive officers, Jeff Smith and Alex Kelly, established Rule 10b5-1 trading plans for stock sales and RSU tax obligations - Chief Research Officer Jeff Smith entered into a **Rule 10b5-1 trading plan** to sell up to **7,931 shares** of common stock between May 2025 and January 2026[442](index=442&type=chunk) - Chief Financial Officer Alex Kelly entered into a **Rule 10b5-1 sell-to-cover instruction** to sell shares to cover tax obligations from vesting RSUs[443](index=443&type=chunk) [Exhibits](index=84&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including corporate documents and Sarbanes-Oxley certifications

Core Viewpoint - Precision BioSciences' shares surged 23.8% following the FDA's Fast Track designation for PBGENE-HBV, a gene editing program aimed at curing chronic hepatitis B by targeting cccDNA and integrated HBV DNA [1][2][3] Company Overview - PBGENE-HBV is the first gene editing program with a unique mechanism of action to enter clinical stages as a potential cure for chronic hepatitis B [3] - The company has received FDA clearance to initiate the phase I ELIMINATE-B study for PBGENE-HBV in the U.S., with simultaneous studies in other regions to enhance patient recruitment [4] - Currently, the company is enrolling patients in the low-dose cohort of the ELIMINATE-B study, with plans to escalate to higher doses in subsequent cohorts [5][7] Market Context - Chronic hepatitis B affects approximately 300 million people globally, with around 2 million in the U.S. facing significant health risks, including cirrhosis and liver cancer [8] - Existing antiviral treatments do not eliminate the virus, necessitating lifelong therapy without achieving a functional cure, highlighting the unmet medical need that PBGENE-HBV aims to address [9] Pipeline and Future Prospects - In addition to PBGENE-HBV, Precision BioSciences has several other gene therapy programs in preclinical evaluation, including a partnered candidate, ECUR-506, for treating neonatal onset ornithine transcarbamylase deficiency [10]

分组1 - Precision BioSciences reported a quarterly loss of $3.20 per share, significantly worse than the Zacks Consensus Estimate of a loss of $0.42, representing an earnings surprise of -661.90% [1] - The company posted revenues of $0.64 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 93.28%, compared to revenues of $7.04 million a year ago [2] - The stock has increased by approximately 33.6% since the beginning of the year, while the S&P 500 has declined by -1.8% [3] 分组2 - The current consensus EPS estimate for the upcoming quarter is -$0.38 on revenues of $10 million, and for the current fiscal year, it is -$1.05 on revenues of $45.6 million [7] - The Medical - Biomedical and Genetics industry is currently ranked in the top 31% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8]

Gene Editing Technology - The ARCUS platform is a novel gene editing technology that utilizes a homing endonuclease, offering a unique cut that drives defined therapeutic outcomes [20]. - PBGENE-HBV, the lead program, aims to eliminate cccDNA in chronic hepatitis B patients, with the first patient dosed in December 2024 and a substantial reduction in HBsAg observed in two of three participants [30][31]. - PBGENE-3243 targets m.3243 associated mitochondrial disease, affecting approximately 20,000 people in the U.S., with plans to submit an IND application in 2025 [33]. - Preclinical data showed ARCUS achieved over 85% gene insertion efficiency in T-cells and 39% in non-dividing primary human hepatocytes [34]. - PBGENE-DMD demonstrated significant improvement in functional effects in DMD-diseased mice, with the ability to edit Pax7+ cells [36]. - PBGENE-LIVER achieved 40% to 45% overall gene insertion efficiency in non-dividing cells in nonhuman primates [37]. Collaborations and Agreements - The Novartis Agreement involves developing a custom ARCUS nuclease for treating hemoglobinopathies, with Novartis responsible for subsequent development and commercialization [38]. - A license agreement with Caribou Biosciences includes upfront payments and royalties on net sales, enhancing the company's collaboration strategy [43]. - On August 15, 2023, Imugene US acquired the manufacturing infrastructure for azer-cel, including clinical trial inventory and related assets, as part of the asset purchase agreement [45]. - The Imugene License Agreement grants Imugene US exclusive and non-exclusive rights to develop and commercialize azer-cel and up to three additional research product candidates [46]. - The Novartis Agreement, effective June 15, 2022, focuses on developing in vivo gene editing products for hemoglobinopathies, including sickle cell disease and beta thalassemia [47]. - Novartis will assume responsibility for all subsequent development, manufacturing, and commercialization activities for the licensed products developed from the ARCUS nuclease [48]. - The Duke License includes milestone payments totaling $0.3 million and low single-digit percentage royalties on net sales of licensed products [52]. Intellectual Property and Patents - The company holds an exclusive license from Duke under 12 issued U.S. patents and two pending U.S. patent applications as of December 31, 2024 [62]. - The patent portfolio includes 45 issued U.S. patents and 46 pending non-provisional U.S. patent applications, with a focus on obtaining additional patent protection for ARCUS technologies [62]. - The company relies on a combination of patents, trade secrets, and licensing agreements to protect its intellectual property and maintain a competitive edge in the market [60]. - The first patent family includes 12 issued patents in the United States, 6 in Europe, 3 in Japan, and 1 each in Australia and Canada, with a standard expiration date of October 18, 2026 [64]. - The second patent family includes 4 issued patents in the United States, 3 in Europe, 2 in Japan, and 1 in Australia, with a standard expiration date of October 31, 2028 [65]. - The third patent family includes 3 issued patents in the United States and 2 each in Europe and Australia, with a standard expiration date of July 14, 2029 [66]. - The fourth patent family has pending applications in multiple countries, with a potential expiration date of May 7, 2040 [67]. - The company owns 30 patent families related to in vivo gene editing technologies, protecting its product candidates [69]. Regulatory and Compliance - The FDA requires the submission of an IND before initiating clinical trials, which becomes effective 30 days after receipt unless safety concerns arise [129]. - Human clinical trials must follow protocols that establish safety, purity, potency, or effectiveness of the proposed biologic product candidate [131]. - The BLA submission includes all relevant data from preclinical and clinical studies, and the FDA aims to review standard applications within 10 months or 6 months for priority reviews [140]. - The FDA may issue a Complete Response Letter (CRL) if the BLA submission is found unacceptable, outlining deficiencies and requesting additional information [141]. - Approval of a product may be granted for specific indications and may require a Risk Evaluation and Mitigation Strategy (REMS) to manage known risks [142]. - The Pediatric Research Equity Act (PREA) mandates pediatric clinical trials for most biologics unless a deferral or waiver is granted [143]. - Fast track designation allows for expedited review of products intended to treat serious conditions and may involve rolling review of the BLA [145]. - Breakthrough therapy designation provides intensive FDA interaction and guidance starting as early as Phase 1 for products showing substantial improvement over existing therapies [146]. - Accelerated approval may be granted based on surrogate endpoints, with confirmatory trials required to verify clinical benefit [147]. - The FDA may withdraw approval of a drug if confirmatory trials fail to verify predicted clinical benefits or if the sponsor does not conduct trials timely [147]. - The Regenerative Medicine Advanced Therapy (RMAT) designation allows for expedited development and review of drugs intended to treat serious or life-threatening diseases, with potential benefits including more frequent FDA meetings and eligibility for accelerated approval [148]. - Orphan Drug Designation can be granted for drugs intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S., providing benefits such as tax credits and a seven-year exclusivity period upon first FDA approval [150][152]. Market and Industry Dynamics - The company competes with major biotechnology firms and academic institutions in the gene editing and therapy sectors, facing significant competition in research and development capabilities [57]. - The ACA has significantly changed healthcare financing and delivery, with ongoing scrutiny over pharmaceutical pricing practices [4]. - The Inflation Reduction Act of 2022 mandates price negotiations for certain drugs starting in 2026, with potential significant impacts on the pharmaceutical industry [4]. - The U.S. federal Anti-Kickback Statute prohibits remuneration to induce purchases of items reimbursable under federal healthcare programs [5]. - The U.S. civil False Claims Act prohibits knowingly presenting false claims for payment to the federal government [6]. - Compliance with healthcare laws involves substantial costs and potential penalties for violations, including exclusion from Medicare and Medicaid programs [7]. Workforce and Culture - The company has a team of 27 full-time employees with Ph.D. or M.D. degrees, emphasizing strong scientific experience in gene therapies [42]. - The organization emphasizes a culture of innovation, accountability, respect, adaptability, and perseverance, aiming to empower employees to deliver meaningful work [218]. - As of December 31, 2024, the workforce was approximately 51% female and 24% from diverse racial backgrounds, with senior leadership being approximately 33% female and 24% Asian or Black [220].

Financial Performance - Total revenues for Q4 2024 were $0.6 million, a decrease of $6.4 million from $7.0 million in Q4 2023, primarily due to the conclusion of the Prevail agreement[25]. - Total revenues for the fiscal year 2024 were $68.7 million, an increase of $20.0 million from $48.7 million in fiscal year 2023, driven by revenue from the Prevail agreement and new license agreements[29]. - Net loss for Q4 2024 was $17.8 million, or $(2.22) per share, compared to a net loss of $16.3 million, or $(4.06) per share, in Q4 2023[28]. - Net income from continuing operations was $7.2 million for the year ended December 31, 2024, a significant improvement from a net loss of $42.5 million in 2023[32]. - The company reported a net income of $7.2 million, or $1.05 per share basic and $1.04 per share diluted for the year ended December 31, 2024, compared to a net loss of $61.3 million, or $(15.96) per share in 2023[33]. - Total revenue for the year ended December 31, 2024, was $68.7 million, compared to $48.7 million in 2023, representing a growth of approximately 41.2%[45]. - Total operating expenses for the year ended December 31, 2024, were $94.9 million, slightly higher than $92.5 million in 2023[45]. Expenses - Research and development expenses increased to $15.9 million in Q4 2024 from $13.4 million in Q4 2023, mainly due to rising costs associated with the PBGENE-HBV program entering clinical trials[26]. - General and administrative expenses rose to $9.6 million in Q4 2024, up from $8.5 million in Q4 2023, attributed to higher employee-related expenses and share-based compensation[27]. - Research and development expenses increased to $59.6 million for the year ended December 31, 2024, up from $53.4 million in 2023, reflecting a $6.2 million rise primarily due to PBGENE-HBV program costs[30]. - General and administrative expenses decreased to $35.3 million for the year ended December 31, 2024, down from $39.1 million in 2023, a reduction of $3.8 million attributed to operational discipline and lower headcount[31]. Cash Position - The company has approximately $108.5 million in cash, cash equivalents, and restricted cash as of December 31, 2024, expected to extend its cash runway into the second half of 2026[24]. - The company had cash, cash equivalents, and restricted cash of $108.5 million as of December 31, 2024, down from $116.7 million in 2023[47]. Clinical Development - PBGENE-HBV demonstrated substantial antiviral activity with a reduction in Hepatitis B surface antigen after the first administration at the lowest dose level[4]. - The first patient cohort for PBGENE-HBV has been dosed, establishing safety and early efficacy, with no Grade ≥2 treatment-related adverse events reported[8]. - The ELIMINATE-B trial for PBGENE-HBV is designed to investigate multiple ascending dose levels in patients with chronic Hepatitis B, targeting a large patient population of approximately 300 million worldwide[5]. - The company plans to provide ongoing updates on clinical data for PBGENE-HBV throughout 2025, with significant milestones expected[11]. - The company plans to provide ongoing updates on the PBGENE-HBV study throughout 2025, including data at higher dose levels[37]. Shareholder Equity - Total stockholders' equity increased to $56.4 million as of December 31, 2024, compared to $18.9 million in 2023[47]. - The weighted average shares outstanding increased to 6,832,982 basic and 6,883,911 diluted for the year ended December 31, 2024, compared to 3,841,405 for both basic and diluted in 2023[34].

Core Insights - The article discusses the author's extensive background in biomedicine and bioengineering, emphasizing over 20 years of experience in the research and development of novel Cell & Gene Therapies (CGT) aimed at addressing various clinical needs [1] Group 1: Company Analysis - The author intends to focus on analyzing biotechnology, pharmaceutical, Medtech, and healthcare stocks, leveraging their expertise in life sciences to evaluate the potential of novel treatments and their ability to generate shareholder returns [1] Group 2: Industry Perspective - The article highlights the growing importance of CGT in the healthcare sector, indicating a significant opportunity for investment in companies that are innovating in this space [1]

Core Insights - Precision BioSciences, Inc. has revealed initial results from the first administration of PBGENE-HBV in cohort 1 of the ELIMINATE-B trial, which targets chronic Hepatitis B patients who are HBeAg-negative [1][4] - The trial is designed to assess PBGENE-HBV at multiple ascending dose levels, with the first dose being 0.2 mg/kg, and aims to establish the optimal dose and administration schedule [2][4] Group 1 - PBGENE-HBV was found to be safe and well tolerated in all three participants of cohort 1 after the initial administration [2][3] - No participants experienced Grade ≥2 treatment-related adverse events or serious adverse events [3] - A significant reduction in Hepatitis B surface antigen (HBsAg) was observed in two of the three participants following the first administration [3] Group 2 - The ELIMINATE-B study is currently enrolling patients in Moldova, Hong Kong, and New Zealand [4] - The company plans to complete subsequent administrations in cohort 1 patients and will escalate to higher dose levels to effectively eliminate covalently closed circular DNA (cccDNA) and inactivate integrated HBV DNA [4] - Precision BioSciences intends to share detailed clinical data throughout 2025 [5] Group 3 - HC Wainwright analyst Patrick Trucchio maintains a Buy rating on Precision BioSciences with a price target of $60 [5] - Following the news, DTIL stock increased by 9.22% to $5.63 [5]