Detalimogene Voraplasmid

Data from pivotal cohort demonstrate compelling clinical activity, consistent with Phase 1 results Favorable tolerability profile with no drug-related discontinuations Detalimogene’s profile to date supports its potential as a foundational therapy for NMIBC BOSTON, MA, USA & MONTREAL. Canada I September 26, 2024 I enGene Holdings Inc. (Nasdaq: ENGN or “enGene” or the “Company”), is a clinical-stage genetic medicines company whose non-viral lead investigational product detalimogene voraplasmid (also known as detalimogene, and previously EG-70) is in an ongoing pivotal study in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (Cis). Today, the Company announced preliminary data from 21 patients assessed at three months, including 17 patients who were also assessed at six months, in the ongoing pivotal cohort of the LEGEND study. The Complete Response (CR) rate at any time was 71%, the CR rate at three months was 67% and the CR rate at six months was 47%. Detalimogene was generally well-tolerated by patients and no patients discontinued due to treatment-related adverse events. “We are pleased with this preliminary dataset, which clearly demonstrates that detalimogene is highly active and generally well tolerated. The data are consistent with what was observed in Phase 1 and give us increased confidence in the emerging profile,” said Raj Pruthi, M.D., Chief Medical Officer of enGene. “We are also planning protocol refinements in LEGEND, which we believe will provide patients with additional clinical benefit.” “The promising initial efficacy and safety data observed in LEGEND’s pivotal cohort, combined with detalimogene’s ease of handling, administration, minimal storage requirements, and lack of post-procedural patient restrictions underscore its potential to become a broadly utilized treatment option for NMIBC patients, especially in the community practice setting,” remarked Suzanne Merrill, M.D., a urologist specializing in bladder cancer with the United Urology Group in Colorado. Bladder cancer is a top 10 cancer by incidence in the US with high annual treatment cost. NMIBC represents more than 75% of bladder cancer diagnosis and over 70% of urologists practice in the community setting where the majority of these patients are treated. “Detalimogene was designed to be the most practical therapy for urologists to manage NMIBC,” said Ron Cooper, Chief Executive Officer of enGene. “The early results from our pivotal LEGEND study clearly demonstrate that detalimogene has the potential to offer a highly differentiated profile by striking an optimal balance between efficacy, tolerability, and ease of use.” Safety Information The overall tolerability profile associated with detalimogene was favorable, and there have been no drug-related discontinuations in the study.  Of the 42 patients assessed for safety, inclusive of all Phase 2 cohorts, 20 patients (48%) experienced at least one treatment-related adverse event (TRAE), which were mainly Grade 1/2 in severity, except for two Grade 3 TRAEs (peripheral edema and urosepsis). The most common TRAEs (≥10%) were dysuria, bladder spasm, pollakiuria and fatigue. There were no Grade 4 or Grade 5 TRAEs reported. About LEGEND The LEGEND study is a multi-cohort study to establish efficacy of detalimogene in high-risk NMIBC patients with Cis, as well as those with papillary-only NMIBC. The pivotal cohort is an approximately 100 patient, open-label study evaluating detalimogene in BCG-unresponsive NMIBC patients with Cis. Patients receive 800µg/mL of detalimogene intravesically at weeks one, two, five, and six during a 12-week cycle, for up to four cycles, with assessments at three, six, nine, and 12 months. The study’s primary efficacy endpoint is the percentage of patients with a complete response at 12 months, based on cystoscopy, urine cytology and biopsy. In addition to LEGEND’s pivotal cohort, the Company plans to initiate enrollment of three additional cohorts in the LEGEND study: (i) high-risk BCG-exposed patients with Cis and BCG-naïve patients with Cis in cohorts 2a and 2b, respectively, and (ii) high-risk BCG-unresponsive NMIBC patients with papillary-only disease in cohort 3. Enrollment for cohorts 2a, 2b, and 3 is expected to begin in the fourth quarter of 2024. The Company remains on track to file a Biologics License Application (BLA) for detalimogene in its pivotal cohort in mid-2026. About enGene enGene is a clinical-stage biotechnology company mainstreaming genetic medicines through the delivery of therapeutics to mucosal tissues and other organs, with the goal of creating new ways to address diseases with high clinical needs. enGene’s lead program is detalimogene voraplasmid, (also known as detalimogene, and previously EG-70) for patients with Non-Muscle Invasive Bladder Cancer (NMIBC) – a disease with a high clinical burden. Detalimogene is being evaluated in the ongoing multi-cohort LEGEND Phase 2 study, which includes a pivotal cohort studying detalimogene in Bacillus Calmette Guérin (BCG)-unresponsive patients with carcinoma in situ (Cis). Detalimogene was developed using enGene’s proprietary Dually Derivatized Oligochitosan (DDX) platform, which enables penetration of mucosal tissues and delivery of a wide range of sizes and types of cargo, including DNA and various forms of RNA. For more information, visit enGene.com. SOURCE: enGene

A small US and Canadian gene therapy biotech has released a look at data from its experimental bladder cancer treatment, hoping to enter a field that includes CG Oncology, ImmunityBio, Johnson & Johnson and UroGen. EnGene said Thursday that its non-viral gene therapy led to a complete response in 71% of 21 patients assessed so far in the key cohort of its Phase 2 LEGEND trial. It’s one of several drugmakers testing treatments for patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer, or NMIBC. Known as detalimogene voraplasmid or EG-70, enGene’s therapy is delivered to the bladder using a catheter four times during a 12-week cycle, for up to four cycles. EnGene said the treatment was “generally well-tolerated” and that no patients stopped the study because of drug-related safety concerns. Most side effects were grade 1 or 2 in severity, with two cases — peripheral edema and urosepsis — reaching grade 3. The biotech expects to collect data on about another 80 patients from the pivotal cohort portion of the open-label study before requesting regulatory approval. But enGene said it plans to package the data into a biologics license application in the middle of 2026 — about one year later than originally projected when the company went public by way of a SPAC combination last November. “The original guidance was more of an estimate, not based on experience. Now that we have a number of sites up and going, we see the enrollment coming in, we feel pretty confident about our [new] guidance,” Ron Cooper, who took over as CEO this summer , said in an interview. Merck’s product BCG is the standard treatment for patients with certain forms of the cancer, but the treatment is in shortage and doesn’t help all patients. Merck has said it expects to finish constructing a new facility to make BCG in Durham, NC, by late 2026. ImmunityBio’s IL-15 agonist Anktiva secured FDA approval in certain patients with the cancer in April, about 11 months after originally being rejected . The drug was approved in combination with BCG, however, meaning it doesn’t assuage concerns about the standard-of-care’s ongoing supply constraints. J&J is also working on a so-called “ pretzel ” drug-device combo. And UroGen is looking to treat patients with certain forms of NMIBC with a decades-old chemotherapy delivered as a gel . Last month, it asked the FDA for approval. CG Oncology, meanwhile, reported interim data from its Phase 3 in May, showing that 75.2%, or 79 out of 105 patients, had a complete response at any time to its therapy called cretostimogene grenadenorepvec. In enGene’s Phase 2 pivotal cohort, the complete response rate was 71% at any time, but it fell to 67% at three months and 47% at six months. For comparison, the complete response rate in CG’s Phase 3 was 63.6% at six months , but in a Phase 2 study, that rate was 44% . As it progresses with the rest of the pivotal trial, enGene said it is making protocol amendments to “reflect what’s done in clinical practice,” according to chief medical officer Raj Pruthi, a urological oncologist who joined the company in April after working on bladder cancer at J&J. “One of the amendments we’ve made recently is involving re-resection of T1 tumors,” Pruthi said. Another adjustment, at three months, is allowing for resection and reinduction of therapy for patients who have recurrence. “That reinduction of therapy is something that’s very familiar to us as urologists from the standpoint of that’s what we have done for years with BCG. And other late-stage agents and even ones approved by the FDA have also employed this reinduction paradigm.” CG has said it expects more data by the end of this year and plans to package the results for an approval request to the FDA. The biotech’s immunotherapy deploys a virus to infect and dismantle tumor cells. It had the first and biggest biotech IPO $CGON of the year, reeling in $380 million in January .