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.

LEGEND Pivotal Cohort Protocol Amendment - The current LEGEND protocol includes changes such as performing a 2nd resection at the lesion site and restaging, which aligns with the standard of care and AUA Guidelines[8] - Enrollment is complete with 125 patients in the pivotal cohort, with 94 patients (75%) enrolled post-amendment and 31 patients (25%) pre-amendment[10, 11] Efficacy Data - Post-protocol amendment, the Intent-to-Treat (ITT) population (N=62) showed a Complete Response (CR) rate of 63% at any time, 56% at 3 months, and 62% at 6 months[14] - Pre-protocol amendment, the ITT population (N=31) showed a CR rate of 55% at any time, 55% at 3 months, and 41% at 6 months[18] - The 6-month CR rate for detalimogene post-amendment is 62%, which is trending competitively with novel products in the industry[25] Tolerability and Safety - In the entire Cohort 1 (n=125), 42.4% of patients experienced at least one Treatment-Related Adverse Event (TRAE), with zero discontinuations due to adverse events[30] - Detalimogene is trending towards best-in-class tolerability compared to other investigational agents and approved products, with a serious TRAE rate of 1.6%[31] Trial Progress and Enrollment - Enrollment rate was heavily skewed to the last 10 months, delaying insights into long-term efficacy[28, 35] - Additional cohorts are in progress, including BCG-Naïve, BCG-Exposed, and Papillary-Only NMIBC, with varying enrollment statuses[33]

enGene Holdings Inc. (NASDAQ:ENGN) stock is edging higher on Tuesday, with a session volume of 18.62 million compared to an average volume of 266.85 thousand, as per data from Benzinga Pro.ENGN is reaching significant price levels. Check the full analysis hereenGene on Tuesday reported additional preliminary data from the pivotal cohort of its ongoing, Phase 2 LEGEND trial of detalimogene voraplasmid (also known as detalimogene and previously EG-70) in high-risk bladder cancer patients.The trial included 99 ...

BOSTON & MONTREAL--(BUSINESS WIRE)--enGene Holdings Inc. (Nasdaq: ENGN or "enGene†or the "Company†), a clinical-stage, non-viral genetic medicines company, today reported additional preliminary data from the pivotal cohort of its ongoing, Phase 2 LEGEND trial of detalimogene voraplasmid (also known as detalimogene and previously EG-70) in high-risk, Bacillus Calmette-Guérin (BCG)- unresponsive non-muscle invasive bladder cancer (NMIBC) patients with carcinoma in situ (CIS) with or without conco. ...

Detalimogene Voraplasmid & Market Opportunity - The Non-Muscle Invasive Bladder Cancer (NMIBC) market is forecasted to be greater than $20 billion [11] - NMIBC represents 75-80% of bladder cancer diagnoses [14] - Approximately 25,000 US patients per year are diagnosed with High-Risk NMIBC [15] Clinical Trial & Efficacy - The LEGEND study is a global, single-arm, open-label study with a target enrollment of 125 patients with BCG-Unresponsive High-risk NMIBC with CIS [49] - In the post-protocol amendment group (N=62), the Any Time Complete Response (CR) rate was 63% (CI: 51-74) [55, 58] - In the pre-protocol amendment group (N=31), the Any Time Complete Response (CR) rate was 55% (CI: 38-71) [59] Safety & Tolerability - In the Cohort 1 study (n=125), 42.4% of patients experienced at least one Treatment-Related Adverse Event (TRAE) [62] - The most common TRAEs reported in >10% of patients were fatigue (16.8%), dysuria (12.0%), bladder spasm (10.4%), micturition urgency (10.4%), and pollakiuria (10.4%) [62] - Only 1.6% of patients experienced TRAEs leading to dose interruptions, and 0.8% led to dose discontinuations [62] Operational & Financial - Buy+Bill has grown from 5% of revenue in 2008 to 15-20% in 2025 [32] - The company projects its current capital to provide runway into 2027 [78]

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]

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 [8][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][5] 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, potentially enhancing the profile of detalimogene voraplasmid [5][9] - The company is focusing on pivotal cohort 1 while also initiating additional cohorts to expand knowledge and data for treating urologists [17] 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 [14][15] - The company is confident in its manufacturing capabilities, which are crucial given the challenges faced in the industry [15] Company Strategy and Development Direction - The company aims to provide incremental data updates as more patients are enrolled under the new protocol, which is expected to improve the overall profile of the treatment [1][2] - There is a focus on aligning the treatment protocol with standard care to enhance the drug's marketability and acceptance among urologists [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed excitement about the upcoming data and the potential for the treatment to meet regulatory standards, emphasizing the importance of the new protocol [1][14] - The management highlighted the challenges in the industry related to manufacturing but expressed confidence in their current capabilities and readiness for the BLA submission [15] Other Important Information - The company is actively enrolling patients in three new cohorts to gather more data, which will help in understanding the treatment's efficacy across different patient profiles [17] - The management cautioned against making direct comparisons between different studies due to variations in protocols and patient populations [12][13] Q&A Session Summary Question: How many patients from the new protocol? - The majority of patients will be under the new protocol, with a target enrollment of 100 patients achieved [3][5] Question: Could you talk about the bar for the CR rate? - The FDA has approved agents with CR rates between 20% to 40%, while the company reported a 71% CR rate, indicating strong efficacy [8][9] Question: What are the caveats for cross-file comparisons? - Management advised caution in comparing CR rates across studies due to differences in protocols and patient heterogeneity [12][13] Question: Can you touch on BLA filing and confidence to be on track? - The company is on track for a BLA submission in the second half of 2026, with many modules already prepared [14][15] Question: What are the new cohorts and their opportunities? - The new cohorts aim to expand knowledge for treating urologists, with a focus on pivotal cohort 1 for generating critical data [17]

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 [8][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][5] 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, potentially enhancing the profile of detalimogene voraplasmid [3][5] - The company is focused on generating data from the pivotal cohort (cohort 1) while also initiating additional cohorts to expand knowledge in the community [17] 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 [14][15] - The company has noted that the manufacturing process is already at scale, which is a competitive advantage in an industry facing manufacturing challenges [15] Company Strategy and Development Direction - The company aims to provide as much data as possible to treating urologists, indicating a commitment to transparency and education within the medical community [17] - The strategic focus is on aligning the protocol with standard care to improve the treatment profile and increase the likelihood of regulatory approval [9][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the efficacy of detalimogene voraplasmid, especially after protocol changes that align with standard care [9][10] - The management team is optimistic about the upcoming data releases and the potential for a successful BLA filing, highlighting the strength of their regulatory and clinical teams [14][15] Other Important Information - The company is cautious about making cross-study comparisons due to the small sample sizes and variability in patient populations across studies [12][13] - The management emphasized the importance of understanding the heterogeneity of patients in clinical trials, which can affect treatment outcomes [12][13] Q&A Session Summary Question: How many patients from the new protocol? - The majority of patients will be under the new protocol, with a target enrollment of 100 patients, likely to exceed this number [3][5] Question: Could you talk about the bar for the CR rate? - The FDA has approved agents with CR rates between 20% to 40%, while the company reported a 71% CR rate, indicating strong efficacy [8][9] Question: What are the caveats for cross-file comparisons? - The management cautioned against comparisons due to differences in study protocols and patient heterogeneity, emphasizing the need for careful interpretation of CR rates [12][13] Question: Can you touch on BLA filing and confidence? - The company is on track for a BLA submission in the second half of 2026, with many modules already prepared, indicating strong readiness [14][15] Question: What are the new cohorts and their opportunities? - The company initiated three new cohorts to expand knowledge, focusing primarily on the pivotal cohort while also enrolling patients in the others [17]