Summary of enGene Holdings Conference Call Company Overview - **Company**: enGene Holdings (NasdaqCM: ENGN) - **Focus**: Non-viral gene therapy for various diseases, specifically targeting non-muscle invasive bladder cancer (NMIBC) with its lead asset, detalimogene voraplasmid [1][2] Core Product Insights - **Lead Asset**: Detalimogene voraplasmid - **Indication**: Non-muscle invasive bladder cancer (NMIBC) - **Market Potential**: Projected to grow to over $20 billion due to a shift from an incident-based to a prevalent-based disease model [2] - **Efficacy and Tolerability**: Demonstrated promising efficacy and tolerability, with a focus on ease of use for both community and academic urologists [2][3] Market Dynamics - **Current NMIBC Statistics**: Approximately 730,000 cases in the U.S., with 65,000 new cases annually [3] - **Treatment Landscape**: Current management involves BCG therapy, which has been in chronic backorder and presents challenges in administration [4][5] - **Unmet Needs**: Significant unmet needs in the NMIBC market, particularly in community settings where most urologists practice [5][6] Competitive Advantages - **Non-Viral Approach**: Overcomes limitations of viral gene therapies, such as genetic payload size, redosing issues, and high manufacturing costs [3] - **Ease of Administration**: Detalimogene can be administered intravesically with minimal logistical requirements, making it suitable for community practices [12][14] - **Cost-Effectiveness**: Competitive cost of goods due to simple manufacturing processes [12][18] Clinical Development - **Pivotal Program**: Fully enrolled pivotal program for NMIBC patients unresponsive to BCG, with 125 patients enrolled [9] - **Efficacy Data**: Six-month complete response (CR) rate of 62%, showing improvement from pre-protocol rates [11][13] - **Tolerability Profile**: Mostly grade 1 or 2 adverse events, with low rates of dose interruptions (1.6%) and discontinuations (0.8%) [11][14] Future Outlook - **Regulatory Plans**: Anticipated filing with the FDA in the second half of next year, with potential approval in 2027 [2][19] - **Market Growth**: NMIBC market currently valued at approximately $2 billion, expected to grow significantly [18] - **Strategic Positioning**: Detalimogene is positioned to integrate into community urologist practices without disrupting existing workflows, offering a more patient-friendly treatment option [18][19] Conclusion - **Company's Financial Health**: Well-capitalized with over $100 million raised recently, providing a strong foundation for future growth and development [17][18] - **Commitment to Innovation**: enGene is focused on delivering effective and accessible treatments for NMIBC, aiming to improve patient outcomes and streamline urologist practices [16][19]

Summary of enGene Holdings Conference Call Company Overview - **Company**: enGene Holdings (NasdaqCM: ENGN) - **Focus**: Development of non-viral gene therapies for bladder cancer, specifically targeting non-muscle invasive bladder cancer (NMIBC) Industry Context - **Disease Prevalence**: NMIBC affects approximately 730,000 patients in the US, with about 85,000 new cases annually [1][2] - **Market Size**: The management of NMIBC is estimated to cost the healthcare system $6.5 billion per year [3] - **Current Treatment Landscape**: Traditional treatments include BCG therapy, IV chemotherapy, and radical cystectomy, which are often associated with high morbidity and mortality [4][5] Core Product Insights - **Product**: Detalimogene voraplasmid, a non-viral gene therapy designed for intravesical administration [7] - **Mechanism**: Combines plasmid DNA with RIG-I agonists and IL-12 to activate both innate and adaptive immune systems [7] - **Manufacturing**: Utilizes four simple ingredients, allowing for competitive cost of goods and easier handling [8] Clinical Development - **LEGEND Program**: Focused on BCG-unresponsive NMIBC patients, with 125 patients enrolled in the pivotal cohort [8][10] - **Efficacy Data**: - 63% complete response (CR) rate at any time for post-amendment patients [11] - 62% CR rate at six months, showing improvement over previous data [11][13] - **Tolerability**: 42% treatment-related adverse event rate, primarily mild and associated with catheterization [14][15] Competitive Landscape - **Comparison with Other Products**: Detalimogene's efficacy and tolerability are competitive with other approved products, such as those from J&J [18][19] - **Market Positioning**: Positioned as a first-line treatment option for busy community urologists, emphasizing ease of use and integration into practice [21][27] Regulatory and Future Outlook - **FDA Engagement**: Ongoing discussions with the FDA regarding clinical endpoints and potential approval timelines, with a target for filing in the second half of next year and potential approval in 2027 [21] - **Financial Position**: Company has sufficient cash reserves to support operations through 2027 [21] Additional Insights - **Community Urologist Feedback**: There is enthusiasm for new products, including J&J's TAR-200, which is expected to integrate well into existing treatment workflows [22][23] - **Importance of Durability**: While CR at any time is a primary endpoint, durability of response is also critical for treatment decisions, especially for older patients with multiple options [25][26] Conclusion - enGene Holdings is positioned to address significant unmet needs in the NMIBC market with its innovative non-viral gene therapy, which offers a competitive profile in terms of efficacy, tolerability, and ease of use for healthcare providers. The company is on track for potential regulatory approval and is well-prepared to capitalize on emerging market opportunities.

Summary of enGene Holdings Conference Call on DETALIMGENE Company Overview - **Company**: enGene Holdings (NasdaqCM: ENGN) - **Focus**: Development of DETALIMGENE, a non-viral gene therapy for high-risk BCG unresponsive non-muscle invasive bladder cancer (NMIBC) Key Points from the Conference Call Industry Context - **Target Disease**: High-risk BCG unresponsive NMIBC, particularly carcinoma in situ (CIS) - **Current Treatment Landscape**: Limited options for patients who progress to BCG unresponsive disease, with radical cystectomy being a last resort due to high morbidity and mortality rates [doc id='22'][doc id='23'] Clinical Trial Updates - **Enrollment**: Completion of enrollment in the pivotal cohort with 125 patients, exceeding the original target by 25% due to investigator demand [doc id='3'][doc id='4'] - **Protocol Amendments**: Significant changes made to align the trial with standard care, including re-resection requirements for T1 lesions and biopsy confirmations for persistent CIS [doc id='8'][doc id='9'] - **Efficacy Data**: - Six-month complete response (CR) rate increased to 62% post-amendment, compared to previous rates of 47% [doc id='4'][doc id='12'] - Anytime CR rate reported at 63% [doc id='10][doc id='14'] - High-risk patient characteristics noted, with 42% having concurrent papillary disease [doc id='10][doc id='41'] Safety and Tolerability - **Adverse Events**: 42% of patients experienced treatment-related adverse events, mostly mild (grade one or two) [doc id='17'] - **Discontinuation Rates**: Very low treatment discontinuation (0.8%) and interruption (1.6%) rates, indicating a favorable safety profile [doc id='17] Competitive Positioning - **Differentiation**: DETALIMGENE is positioned as a potentially best-in-class therapy due to its ease of use, tolerability, and competitive efficacy [doc id='5][doc id='30] - **Market Readiness**: Anticipation of high uptake among providers due to its non-viral nature and reduced logistical burdens compared to existing therapies [doc id='38][doc id='39] Future Outlook - **Regulatory Engagement**: Plans to engage with the FDA regarding the statistical analysis plan (SAP) and patient inclusion criteria for final analysis [doc id='15][doc id='36] - **Long-term Data**: Expectation of 12-month data availability in the second half of 2026, with a BLA filing planned for the same period [doc id='30][doc id='29] Insights from Clinical Experts - **Real-world Management**: Insights shared by Dr. Suzanne Merrill on the challenges of managing NMIBC and the importance of bladder-sparing therapies [doc id='20][doc id='23] - **Treatment Selection**: Emphasis on the need for individualized treatment strategies based on efficacy, safety, and logistical considerations [doc id='24][doc id='45] Conclusion - **Overall Sentiment**: Positive outlook on DETALIMGENE's potential to provide a new treatment option for NMIBC patients, with a focus on improving patient quality of life and reducing the burden on healthcare providers [doc id='30][doc id='27]

Summary of enGene Holdings FY Conference Call Company Overview - **Company**: enGene Holdings (NasdaqCM: ENGN) - **Focus**: Non-viral gene therapy utilizing the Dually Derivatized Oligochitosan (DDX) platform - **Lead Asset**: Detalimogene voraplasmid, targeting non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) resistant to Bacillus Calmette-Guérin (BCG) [2][3] Industry Context - **Bladder Cancer Statistics**: - Sixth most common cancer in the U.S. - Approximately 780,000 patients currently, with 82,000 new cases annually [5] - **Current Treatment Landscape**: - BCG is the standard treatment but is often on backorder, leading to radical cystectomy in many cases [5] Core Points and Arguments - **Efficacy and Tolerability**: - Detalimogene voraplasmid shows a 71% complete response (CR) rate with good tolerability [7][10] - Compared to existing products with CR rates of 20% to 40% [8] - **Ease of Administration**: - No pre-washes, special handling, or co-medications required, making it more suitable for busy community urology practices [9][10] - **Protocol Changes in LEGEND Study**: - Implemented three protocol amendments to enhance efficacy, including stricter enrollment criteria for T1 patients and allowing resection of TA [13][16] - **Regulatory Confidence**: - High confidence in the registrational path, supported by FDA engagement and recent designations [20] Competitive Landscape - **Differentiation from Competitors**: - Detalimogene voraplasmid is non-viral, contrasting with newer products that may require complex handling [11][12] - **Market Positioning**: - Targeting community urologists who may not be tracking new medications closely, focusing on the product's efficacy and ease of use [22] Future Outlook - **Clinical Development**: - Anticipated data updates in Q4 of the current year, with a BLA filing expected in mid-next year and potential approval in 2027 [28] - **Cash Position**: - Over $250 million in cash, sufficient to fund operations into 2027 [28] - **Expansion Beyond Bladder Cancer**: - Potential applications of the DDX platform in other cancers and mucosal delivery systems [26][27] Additional Insights - **AI Integration**: - enGene is exploring AI's potential to enhance drug development and commercialization processes [33][34] - **Regulatory Environment**: - Positive interactions with the FDA, indicating a supportive regulatory landscape for enGene's products [35][36] Conclusion - enGene Holdings is positioned to address significant unmet needs in bladder cancer treatment with its innovative non-viral gene therapy platform, demonstrating strong efficacy, tolerability, and ease of use, while maintaining a solid financial position and regulatory support for future growth.

Financial Data and Key Metrics Changes - The company reported a complete response (CR) rate of 71% in the September 2024 update, indicating a strong efficacy profile for detalimogene voraplasmid [3][9] - The target enrollment for the study has been reached at 100 patients, with expectations to exceed this number, which is a significant increase from the previous cohort of 21 patients [3][15] Business Line Data and Key Metrics Changes - The majority of patients enrolled in the study will be under the new protocol, which aligns with standard care practices, enhancing the profile of detalimogene voraplasmid [3][5] - The company is focusing on pivotal cohort 1 while also initiating additional cohorts to expand knowledge and data for treating urologists [19] Market Data and Key Metrics Changes - The company is preparing for a Biologics License Application (BLA) submission in the second half of 2026, indicating a strategic timeline for regulatory approval [15][16] - The company is confident in its manufacturing capabilities, which are crucial given the challenges faced in the industry [16] Company Strategy and Development Direction - The company aims to provide incremental data updates to enhance the understanding of detalimogene voraplasmid's efficacy and safety profile [3][9] - There is a strong emphasis on aligning the study protocols with standard care to improve the treatment profile and increase the likelihood of regulatory approval [10][15] Management's Comments on Operating Environment and Future Outlook - Management expressed excitement about reaching target enrollment and the potential for sharing more data in the future, which is expected to strengthen the company's position in the market [10][21] - The management highlighted the importance of understanding the heterogeneous nature of NMIBC patients when interpreting efficacy data [14] Other Important Information - The company has initiated three new cohorts to gather more data, focusing on different patient profiles, which will help in expanding the knowledge base for the treatment [19] - The management is cautious about making cross-study comparisons due to the small sample sizes and variability in patient characteristics [13][14] Q&A Session Summary Question: How many patients from the new protocol? - The vast majority of patients will be under the new protocol, with a target enrollment of 100 patients, likely to exceed this number [3] Question: Could you discuss the CR rate expectations? - The FDA has approved agents with CR rates between 20% to 40%, while the company reported a 71% CR rate, indicating confidence in the drug's efficacy [9] Question: What is the timeline for BLA filing? - The company updated its guidance for BLA submission to the second half of 2026, with strong regulatory and clinical teams ready to proceed [15][16] Question: Can you elaborate on the new cohorts? - The new cohorts aim to expand knowledge for treating urologists, with a focus on pivotal cohort 1 being the highest priority [19]