Core Insights - Passage Bio and PepGen are small-cap medical companies being compared based on various financial and operational metrics to determine which stock is more favorable [1][3][4]. Institutional Ownership - Passage Bio has 53.5% of its shares owned by institutional investors, while PepGen has 58.0% [1]. - Insider ownership stands at 5.0% for Passage Bio and 5.2% for PepGen, indicating a similar level of insider investment [1]. Analyst Ratings - Passage Bio has a consensus target price of $42.67, suggesting a potential upside of 363.26% [3][4]. - PepGen's consensus target price is $10.00, indicating a potential upside of 83.82% [3][4]. - Passage Bio has a stronger consensus rating with a score of 2.50 compared to PepGen's score of 2.33 [3]. Earnings and Valuation - Passage Bio reported a net income of -$64.77 million with an earnings per share (EPS) of -$14.40 [5]. - PepGen's net income is -$89.98 million with an EPS of -$2.82 [5]. - Passage Bio has a higher price-to-earnings ratio compared to PepGen, which is currently trading at a lower valuation [5]. Profitability - Passage Bio has a net margin of -102.09% and a return on equity of -52.97% [6]. - PepGen's net margin is -84.15% with a return on equity of -65.59% [6]. Risk & Volatility - Passage Bio has a beta of 1.86, indicating it is 86% more volatile than the S&P 500 [7]. - PepGen has a beta of 1.91, meaning it is 91% more volatile than the S&P 500 [7]. Summary - PepGen outperforms Passage Bio in 6 out of 11 factors compared [8].

Summary of Passage Bio FY Conference Call Company Overview - **Company**: Passage Bio (NasdaqGS:PASG) - **Industry**: Gene Therapy - **Focus**: Lead clinical program in frontotemporal dementia (FTD) with a granular mutation and a preclinical program in Huntington's disease [2][3] Key Points and Arguments Clinical Program Insights - **FTD Program**: The primary focus of the discussion was on the FTD program, particularly following a disappointing phase three study from a competitor [3][11] - **Progranulin Levels**: The company is investigating the significance of progranulin levels in the context of FTD GRN patients, noting that the average CSF progranulin level in a competitor's study was 4-5 ng/ml, while the normal range is 3-8 ng/ml [4][22] - **Mechanism of Action**: Passage Bio's approach involves using AAV (adeno-associated virus) to increase intracellular progranulin levels, contrasting with competitors that may inhibit natural cellular processes [8][25] Study Design and Patient Population - **Patient Selection**: The company plans to focus on earlier-stage patients (CDR 0.5 and 1) to enhance the likelihood of observing clinical responses, as opposed to including more severe patients [14][26] - **Epidemiology**: There are approximately 3,000 to 6,000 patients in the U.S. with FTD GRN, and genetic testing is crucial for early diagnosis [16][18] Regulatory Considerations - **FDA Guidance**: Recent FDA guidance indicates a potential openness to single-arm studies for rare diseases, which could benefit Passage Bio's registration strategy [21][29] - **Statistical Analysis Plan**: The company emphasizes the importance of prespecifying the statistical analysis plan and intends to engage with the FDA early in the study design process [28][29] Manufacturing and Financials - **Manufacturing**: The company collaborates with Catalent for manufacturing, utilizing a high productivity suspension process that can treat over 1,000 patients per batch [43][44] - **Cash Position**: Passage Bio has a cash balance sufficient to sustain operations into 2027, with an annual expenditure of approximately $30 million [45] Additional Important Insights - **Natural History Studies**: The company can leverage data from large natural history studies (All FTD and GenFi) to inform its clinical program [32] - **Neurofilament Biomarker**: The increase in plasma neurofilament levels observed in the study is consistent with age-related changes, suggesting the potential efficacy of the therapy [34][35] - **Future Data Release**: The company plans to refresh data in the first half of next year and will seek FDA guidance on the registration path, which is seen as a critical catalyst for investor confidence [39][40] This summary encapsulates the key aspects of Passage Bio's conference call, highlighting the company's strategic focus, clinical insights, regulatory considerations, and financial health.

Financial Performance - As of September 30, 2025, Passage Bio reported total assets of $74,160,000, a decrease of 27.6% from $102,412,000 on December 31, 2024[13] - For the three months ended September 30, 2025, net loss was $7,749,000, a reduction of 60% compared to a net loss of $19,340,000 for the same period in 2024[14] - The net loss per share for the three months ended September 30, 2025, was $2.44, compared to $6.15 for the same period in 2024[14] - The company reported a comprehensive loss of $7,749,000 for the three months ended September 30, 2025, compared to $19,241,000 for the same period in 2024[14] - For the nine months ended September 30, 2025, the net loss was $32.5 million, a decrease from a net loss of $52.0 million in the same period of 2024, representing a 37.4% improvement[23] - The company reported net losses of $7.7 million and $19.3 million for the three months ended September 30, 2025 and 2024, respectively[168] Cash and Liquidity - The company’s cash and cash equivalents increased to $52,773,000 from $37,573,000, representing a growth of 40.3%[13] - The company reported cash and cash equivalents of $52.8 million at the end of the period, up from $32.3 million at the end of September 2024, reflecting a 63.7% increase[23] - As of September 30, 2025, the company had cash and cash equivalents of $52.8 million, expected to fund operations into Q1 2027[171] - Cash flows used in operating activities amounted to $25.0 million for the nine months ended September 30, 2025, compared to $39.5 million for the same period in 2024, indicating a 36.5% reduction in cash outflows[23] - The company anticipates needing additional funds for operational needs and capital requirements for clinical trials and research and development expenditures[207] Research and Development - Research and development expenses decreased to $4,307,000 from $8,656,000, reflecting a decline of 50.3% year-over-year[14] - Total research and development expenses for the nine months ended September 30, 2025, were $17.9 million, down 41.6% from $30.6 million in the same period of 2024[141] - The company expects research and development expenses to remain consistent in the near future, with potential increases if product candidates progress to later-stage clinical trials[186] - The lead clinical product candidate, PBFT02, is focused on treating frontotemporal dementia caused by progranulin deficiency, aiming to restore lysosomal function[25] - The company has a gene therapy pipeline addressing multiple neurodegenerative diseases, including Alzheimer's disease, with a potential prevalence of 3.9 million in the US/EU[149] Equity and Stock - Total stockholders' equity decreased to $31,120,000 from $61,261,000, a decline of 49.1%[13] - The total number of shares authorized under the Incentive Plan as of September 30, 2025, was 947,598, with 423,039 shares available for future grants[125] - The number of shares reserved for issuance under the Incentive Plan increased by 155,155 shares in January 2025[125] - The company issued 6,000,000 shares under the ATM Facility, resulting in net proceeds of $8.7 million after deducting offering costs of $0.3 million[210] Impairment and Expenses - The company recognized impairment expenses of $2.6 million for long-lived assets during the nine months ended September 30, 2025, compared to $2.7 million for the same period in 2024[45] - The company recorded $2.6 million of impairment expense related to laboratory equipment during the nine months ended September 30, 2025[200] - General and administrative expenses decreased by $3.0 million to $4.3 million for the three months ended September 30, 2025, from $7.3 million in the same period in 2024[195] Workforce and Operational Changes - The company reduced its workforce by approximately 55% in January 2025 to extend its cash runway[85] - Severance and termination-related costs recorded for the nine months ended September 30, 2025, amounted to $1.7 million[86] - A decrease of $3.3 million in wages and benefits due to a lower headcount from restructuring in January 2025[203] Clinical Trials and Product Development - PBFT02, a gene replacement therapy for FTD-GRN, is currently in a Phase 1/2 clinical trial with an active IND application from the FDA[152] - The company has opened enrollment in the upliFT-D study for PBFT02 in FTD-C9orf72 patients, following positive regulatory feedback on the clinical pathway[146] - The company plans to report updated interim safety and biomarker data from Dose 2 in the first half of 2026[164] Lease and Sublease Agreements - The company has classified all leases with terms greater than one year as operating leases as of September 30, 2025[49] - The company is pursuing additional opportunities to sublease space to offset financial obligations under the Laboratory Lease Agreement[101] - Total undiscounted lease payments amount to $38,217,000, with total lease liabilities at $24,337,000 after deducting imputed interest of $13,880,000[102]

Financial Performance - Cash, cash equivalents, and marketable securities were $52.8 million as of September 30, 2025, down from $84.8 million as of September 30, 2024[12] - Net loss for Q3 2025 was $7.7 million, or $2.44 per share, compared to a net loss of $19.3 million, or $6.15 per share, in Q3 2024[12] - Total current assets decreased to $55.7 million as of September 30, 2025, from $78.8 million as of December 31, 2024[15] - Total liabilities increased to $43.0 million as of September 30, 2025, compared to $41.2 million as of December 31, 2024[15] Expenses - Research and Development (R&D) expenses for Q3 2025 were $4.3 million, a decrease of 50.4% compared to $8.7 million in Q3 2024[12] - General and Administrative (G&A) expenses for Q3 2025 were $4.3 million, down 40.4% from $7.3 million in Q3 2024[12] Clinical Trials and Regulatory - Actively enrolling Cohort 3 (FTD-GRN) with 5 to 10 patients and Cohort 4 (FTD-C9orf72) with 3 to 5 patients in the ongoing upliFT-D study[6] - The company is on track to obtain regulatory feedback on the FTD-GRN registrational trial design in the first half of 2026[6] - The company plans to report updated interim safety and biomarker data from Dose 2 in the first half of 2026[6] Manufacturing - A single batch of the new suspension-based PBFT02 manufacturing process is estimated to yield over 1,000 doses with over 90% purity and over 70% full capsids[6]

Core Insights - Passage Bio, Inc. is actively enrolling patients in Cohort 3 (FTD-GRN) and Cohort 4 (FTD-C9orf72) for the ongoing upliFT-D clinical trial of PBFT02, recognizing the urgent need for disease-modifying therapies for frontotemporal dementia (FTD) [1][2] - The company has aligned with the FDA on an analytical approach to establish comparability of a high-productivity, suspension-based manufacturing process for PBFT02, which is expected to yield over 1,000 doses per batch with over 90% purity [5][2] - Passage Bio is on track to obtain regulatory feedback on the registrational trial design for FTD-GRN in the first half of 2026, with plans to report updated interim safety and biomarker data from Dose 2 during the same period [5][4] Recent Highlights - The upliFT-D trial is a Phase 1/2 global, multi-center, open-label clinical trial aimed at evaluating the safety and tolerability of PBFT02, with secondary endpoints including disease biomarkers and clinical outcome measures [6] - The trial protocol has been amended to allow for the enrollment of patients who are prodromal or have mild cognitive impairment, while excluding those with more severe progression [5] Financial Overview - As of September 30, 2025, the company reported cash, cash equivalents, and marketable securities totaling $52.8 million, down from $84.8 million a year prior, with an expected cash runway into the first quarter of 2027 [11] - Research and Development (R&D) expenses for the third quarter of 2025 were $4.3 million, a decrease from $8.7 million in the same quarter of 2024 [11] - General and Administrative (G&A) expenses also decreased to $4.3 million from $7.3 million year-over-year [11] - The net loss for the third quarter of 2025 was $7.7 million, or $2.44 per share, compared to a net loss of $19.3 million, or $6.15 per share, for the same period in 2024 [11][16]

Core Viewpoint - Passage Bio, Inc. is actively engaged in the development of genetic medicines aimed at treating neurodegenerative diseases, with a focus on innovative one-time therapies [3]. Company Overview - Passage Bio is a clinical stage genetic medicines company dedicated to improving the lives of patients suffering from neurodegenerative diseases [3]. - The company's lead product candidate, PBFT02, targets conditions such as frontotemporal dementia by increasing progranulin levels to restore lysosomal function and slow disease progression [3]. Upcoming Events - Will Chou, M.D., the president and CEO of Passage Bio, will participate in a fireside chat at the Guggenheim Securities 2 Annual Healthcare Innovation Conference on November 12, 2025, at 9:30 a.m. ET in Boston, MA [1]. - A live webcast of the event will be accessible on the Investors & News section of Passage Bio's website, with a replay available for 90 days post-event [2].

Summary of Conference Call on Gene Therapy for Neurodegenerative Diseases Industry Overview - The conference focused on gene therapy applications for neurodegenerative diseases, featuring speakers from three companies: Mira, uniQure, and Passage Bio [1][2][6]. Key Points by Company Mira - **Company Overview**: Mira specializes in genetic medicines, focusing on local delivery of small doses to treat severe indications, which enhances safety and reduces costs [2]. - **Recent Milestones**: Mira has two pivotal studies and two awaiting Biologics License Application (BLA) filings, including treatments for rare and common eye diseases and a Parkinson's treatment that has shown three positive studies [3][4]. - **Innovative Approach**: The company utilizes AI technology to analyze data from the largest neurohospital in Europe, demonstrating physiological changes in the brain related to their Parkinson's treatment [4][24]. - **Potential Applications**: Mira's gene therapy can convert glutamate to GABA, potentially treating various neurodegenerative diseases by calming hyperactive neurons [22][24]. uniQure - **Company Overview**: uniQure is a pioneer in genomic medicine, known for developing the first approved AAV gene therapies, including Glybera and Hemgenix [6][9]. - **Lead Program**: The company is focused on Huntington's disease, utilizing a platform called MyCure to suppress the aberrant Huntingtin protein [8]. - **Clinical Findings**: In a study involving 45 patients, uniQure reported a 75% statistically significant slowing of disease progression based on the UHDRS [9]. - **Regulatory Plans**: A pre-BLA meeting is expected in Q4, with a BLA submission planned for Q1 of the following year [9]. Passage Bio - **Company Overview**: Passage Bio is based on technology from the University of Pennsylvania, focusing on gene therapy for frontotemporal dementia and Huntington's disease [14]. - **Clinical Approach**: The company delivers AAV1 via a minimally invasive procedure, showing high levels of target engagement and stabilization of neurofilaments [14][15]. - **Future Directions**: Passage Bio is also developing a preclinical program targeting the DNA damage response pathway in Huntington's disease [15]. Challenges in Gene Therapy - **Delivery Issues**: The primary challenge remains delivering therapies to the correct brain regions, especially for diseases like Huntington's [18][19]. - **Slow Disease Progression**: Designing clinical studies for slowly progressing neurodegenerative diseases is difficult, as changes in function are hard to detect [19][20]. - **Heterogeneity**: Variability among patients complicates the assessment of treatment efficacy, necessitating innovative statistical methods to account for differences [31][32]. Regulatory Considerations - **FDA Flexibility**: The FDA is showing increased willingness to consider alternative trial designs and endpoints for rare diseases with high unmet needs [44][46]. - **Natural History Data**: Utilizing natural history datasets can help in understanding disease progression and support regulatory submissions [30][31]. Safety Concerns - **Patient Safety**: The panel acknowledged the importance of safety in gene therapy, especially following recent patient deaths in trials [35][37]. - **Local Delivery Advantages**: Localized delivery methods may reduce systemic exposure and associated risks, as demonstrated by lower doses used in certain therapies [38][41]. Access and Implementation - **Training and Infrastructure**: Successful implementation of gene therapies will depend on training healthcare providers and establishing treatment centers [52][54]. - **Data-Driven Adoption**: Strong clinical data will be crucial for gaining acceptance among medical professionals and ensuring broad access to therapies [55][56]. Conclusion - The conference highlighted the potential of gene therapy in treating neurodegenerative diseases, the challenges faced in delivery and study design, and the evolving regulatory landscape that may facilitate the development of these innovative treatments [1][17][42].

Core Insights - Passage Bio, Inc. is a clinical stage genetic medicines company focused on neurodegenerative diseases [3] - The company will participate in the Chardan 9th Annual Genetic Medicines Conference on October 21, 2025 [1] - The lead product candidate, PBFT02, aims to treat frontotemporal dementia by elevating progranulin levels [3] Company Overview - Passage Bio is dedicated to developing one-time therapies targeting the underlying pathology of neurodegenerative conditions [3] - The company emphasizes its commitment to improving the lives of patients and families affected by these diseases [4] Event Details - Will Chou, M.D., the CEO, will be part of a panel discussion at the conference [1] - A live webcast of the event will be available on the company's website, with a replay accessible for 90 days [2]

Summary of Passage Bio (PASG) FY Conference Call - September 05, 2025 Company Overview - Passage Bio is a clinical stage genetic medicines company focused on neurodegenerative diseases, particularly frontotemporal dementia (FTD) [2][3] Core Program: PBFT02 - PBFT02 is the lead clinical program targeting frontotemporal dementia with the GRN mutation, addressing a significant unmet need as there are no approved disease-modifying therapies for this condition [2][4] - The target population includes approximately 18,000 patients with GRN mutation FTD and 21,000 with C9orf72 mutation FTD across the U.S. and Europe [3] Clinical Development and Milestones - The ongoing phase 1/2 study of PBFT02 is a multicenter international open-label dose exploration study, currently active in the U.S., Canada, Portugal, and Brazil [7] - Key upcoming milestones include seeking regulatory feedback on manufacturing comparability in Q4 2025 and reporting dose two data in the first half of 2026 [3][21] Mechanism of Action - PBFT02 utilizes AAV gene therapy to increase levels of progranulin, a protein crucial for CNS cell homeostasis, which is deficient in patients with GRN mutation FTD [4][5] - The administration route is intracisterna magna, allowing for broad CNS biodistribution and lower doses compared to systemic delivery [9][10] Clinical Data and Safety Profile - Initial cohorts have shown promising results, with dose one achieving an average of over 25 nanograms per ml of progranulin levels at 12 months, indicating robust and durable responses [15][18] - The safety profile includes three serious adverse events (SAEs) among eight treated patients, with a decision to implement prophylactic anticoagulation for future patients due to observed venous thromboembolic events [12][20] Biomarker Analysis - Plasma neurofilament levels, a marker of neurodegeneration, showed a significant reduction in treated patients compared to the expected annual increase of 29% in untreated patients, suggesting a potential slowing of disease progression [17][20] - The study is also tracking CSF progranulin levels and clinical dementia rating scales to assess treatment efficacy [9][11] Competitive Landscape - PBFT02 is positioned as a potentially best-in-class therapy, with higher and more durable progranulin levels compared to other therapies in development for FTD [18][19] - Market research indicates a preference for a one-time therapy over monthly treatments, particularly for patients with behavioral dementia [19] Future Directions - Plans to expand the clinical study to include FTD C9 patients, as raising progranulin may also benefit TDP-43 pathology seen in multiple neurodegenerative diseases [20][21] - The company has a cash balance of $58 million, providing a runway into Q1 2027 to continue patient treatment and data collection [22] Conclusion - Passage Bio is advancing its clinical program for PBFT02 with promising early data and a clear regulatory pathway, aiming to address significant unmet needs in neurodegenerative diseases [22]

Core Viewpoint - Passage Bio, Inc. (PASG) shows significant potential for upside, with a mean price target of $59.25 indicating a 731% increase from its current trading price of $7.13 [1] Price Targets and Estimates - The average price target for PASG ranges from a low of $10.00 to a high of $120.00, with a standard deviation of $46.71, suggesting a high variability in analyst estimates [2] - The lowest estimate indicates a potential increase of 40.3%, while the most optimistic estimate suggests a 1583% upside [2] - Analysts' consensus on price targets is often questioned, as they may not accurately reflect future stock prices [3][7] Earnings Estimates and Analyst Agreement - Strong agreement among analysts regarding PASG's ability to report better earnings than previously predicted supports the view of potential upside [4] - The Zacks Consensus Estimate for the current year has increased by 30.3% over the past month, with two estimates revised higher and no negative revisions [12] - PASG holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] Implications of Price Movement - While the consensus price target may not be a reliable indicator of potential gains, the direction implied by these targets appears to be a useful guide for further research [14]