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]

Precision BioSciences (DTIL) came out with a quarterly loss of $3.20 per share versus the Zacks Consensus Estimate of a loss of $0.42. This compares to loss of $3.35 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -661.90%. A quarter ago, it was expected that this genome editing company would post a loss of $0.79 per share when it actually produced a loss of $2.83, delivering a surprise of -258.23%.Over the last four quarters, ...

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]

Core Insights - Precision BioSciences' partner iECURE reported promising clinical efficacy and safety data for ECUR-506 in the Phase 1/2 OTC-HOPE study, aimed at treating neonatal-onset Ornithine Transcarbamylase deficiency [1][2] - The treatment was well tolerated in the first patient, with no significant safety concerns apart from mild asymptomatic transaminitis observed at four weeks [2] - BMO Capital Markets upgraded Precision BioSciences, citing early clinical validation for the ARCUS gene editing platform based on the initial data from ECUR-506 [3][5] Company Developments - Precision BioSciences is advancing its PBGENE-HBV program, which aims to deliver a functional cure for chronic hepatitis B, with a Phase 1 trial named ELIMINATE-B currently underway [4] - The company expects to report data from the ELIMINATE-B trial as it progresses through 2025 [4] - BMO Capital analysts predict that the HBV readout in 2025 could lead to a stock price increase of 100-200% or more [5] Market Reaction - Following the positive news regarding ECUR-506, DTIL stock rose by 25.8%, reaching $5.66 [5]

Precision BioSciences (DTIL) came out with a quarterly loss of $2.83 per share versus the Zacks Consensus Estimate of a loss of $0.79. This compares to loss of $3 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -258.23%. A quarter ago, it was expected that this genome editing company would post a loss of $0.77 per share when it actually produced earnings of $3.46, delivering a surprise of 549.35%.Over the last four quarters, t ...

Financial Performance - The company reported a net loss per share of $2.25 for the current quarter, compared to a net loss of $2.10 in the previous quarter[14]. - The net loss for the three months ended September 30, 2024, was $16,425 million, compared to a net loss of $8,079 million in the same period of 2023, indicating a worsening of 103.1%[16]. - For the nine months ended September 30, 2024, the net income was $24,912,000 compared to a net loss of $45,030,000 in the same period of 2023, indicating a significant improvement[20]. - The basic net loss per share for the three months ended September 30, 2024, was $(2.25), compared to $(2.10) for the same period in 2023[130]. Revenue and Growth - Revenue for the three months ended September 30, 2024, was $13,120 million, an increase from $8,079 million in the same period of 2023, representing a year-over-year growth of 62.5%[16]. - The Company recognized revenue of $52.7 million under the Prevail Agreement during the nine months ended September 30, 2024, compared to $23.4 million for the same period in 2023[99]. - Revenue recognized under the TG License Agreement for the nine months ended September 30, 2024, was $8.0 million, with no revenue recognized in the third quarter of 2024[87]. - Revenue recognized under the Novartis Agreement for the three months ended September 30, 2024, was $0.6 million, a decrease from $7.6 million for the same period in 2023[95]. Assets and Liabilities - As of September 30, 2024, total assets decreased to $153.258 million from $159.781 million as of December 31, 2023[12]. - Current liabilities significantly reduced to $11.982 million from $49.987 million as of December 31, 2023[12]. - Total stockholders' equity increased to $64.866 million from $18.861 million as of December 31, 2023[13]. - Cash and cash equivalents at the end of the period were $98,752,000, down from $122,231,000 at the end of the previous year[20]. Operating Expenses - Research and development expenses decreased to $13,084 million for the three months ended September 30, 2024, down from $15,850 million in the same period of 2023, a reduction of 17.5%[16]. - Total operating expenses for the three months ended September 30, 2024, were $21,851 million, compared to $25,483 million in the same period of 2023, reflecting a decrease of 14.4%[16]. - The total lease cost for the year 2024 was $2.022 million, a decrease from $2.530 million in 2023[72]. Funding and Capital - The company will need substantial additional funding to continue its research programs and product development activities[11]. - The Company raised approximately $37.0 million in net proceeds from the March 2024 Public Offering of 2,500,000 shares at $16.00 per share[79]. - The company is focused on raising additional capital to fund ongoing research and development and achieve profitable operations[22]. Competition and Market Conditions - The company faces significant competition in rapidly changing industries, which may impact its financial condition[11]. - The regulatory landscape for therapeutic product candidates is complex and subject to change, which could result in unexpected costs[11]. Stock and Equity - The balance of common shares as of September 30, 2023, was 3,882,739, reflecting an increase from 3,725,689 shares as of December 31, 2022[18]. - The Company has undergone a 1-for-30 reverse stock split effective February 13, 2024, adjusting all historical share amounts accordingly[27]. - As of September 30, 2024, there were 29,935 stock options outstanding under the 2015 Stock Incentive Plan, with no remaining stock options available to be granted[104]. Cash Flow and Financing Activities - Net cash used in operating activities for the nine months ended September 30, 2024, was $39,762,000, a decrease from $75,691,000 in the same period of 2023[20]. - The company reported a net cash provided by financing activities of $44,530,000 for the nine months ended September 30, 2024, compared to $2,559,000 in the same period of 2023[20]. - The Company’s 2024 Term Loan has a principal amount of $22.5 million, used to repay the outstanding balance under the Revolving Line[60]. Future Outlook - The company plans to continue its market expansion and product development strategies to enhance future revenue growth[16]. - The company has incurred significant operating losses since inception and expects to continue incurring losses for the foreseeable future[11]. - The company has a limited operating history, making it difficult to evaluate current business and future prospects[11].

Financial Position - As of September 30, 2024, Precision BioSciences, Inc. expects to report approximately $121 million in cash, cash equivalents, and restricted cash[2]. - The financial results for the quarter ended September 30, 2024, are still under review by the independent registered public accounting firm, which may lead to changes in the reported figures[2]. - Forward-looking statements indicate expectations regarding cash balances, clinical development, and regulatory processes, but actual results may differ due to various risks and uncertainties[5]. Clinical Development - The company received clinical trial application (CTA) clearance in Moldova for its lead candidate, PBGENE-HBV, aimed at treating chronic hepatitis B[3]. - The acceptance of the CTA for the in vivo gene editing program PBGENE-HBV was announced on October 24, 2024[4].