Can Gene Therapy Change Bladder Cancer Treatment?

November 13, 2026

Transcript

Voice over (00:02):

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs (00:38):

Hi, I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for, by, and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model year neobladder and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, producers of this podcast. Today is the latest in a series of podcasts that we’ll be doing again in 2026. In these podcasts, we highlight our pharmaceutical company partners, support of BCAN’s mission of creating better todays and more tomorrows for bladder cancer patients and family. Today, we’re featuring enGene Therapeutics, who was our August 2026 partner in progress. enGene is on a mission to break barriers in genetic medicine and deliver innovative non-viral medicines to improve the quality of life for people with urological cancers.

(01:34):

Well, we’ll be talking today about enGene’s lead investigational candidate, detalimogene voraplasmid. It’s important to remember that different treatments have different results in patients and your results may vary. detalimogene voraplasmid is being evaluated in the ongoing open-label multi-cohort legend trial to establish its safety and efficacy in high risk non-muscle invasive bladder cancer.

(02:00):

I’m pleased to welcome today’s guest, Anthony Cheung. Anthony co-founded enGene and served in various capacities since enGene’s inception, including as president and chief executive officer, and most recently as chief scientific officer overseeing the development and application of enGene’s novel and proprietary Dually Derivatized Oligochitosan DDX, that’s how it’s abbreviated, DDX platform. He has co-authored numerous book chapters, review articles, and peer reviewed journals, and is a named inventor on numerous patents in the areas of gene therapy and polymer chemistry. Anthony, welcome.

Anthony Cheung (02:38):

Thanks, Rick. Thank you for the kind intro and thanks for having me on the podcast.

Rick Bangs (02:41):

Oh, it’s our pleasure. So let’s start with when did you start working in the bladder cancer space and why?

Anthony Cheung (02:48):

Well, it has been quite a long journey to get here. I founded enGene more than 20 years ago with the goal of developing a safe and effective way to deliver genetic medicines directly to mucosal tissues, such as the gut or GI tract, the lungs and the bladder. These tissues are important treatment targets because they are involved in many serious diseases like cancers, inflammatory bowel disease or IBD, cystic fibrosis, and many others. But delivering genetic medicines directly to these tissues can be very difficult. Given that these tissues are the first line of defense against invasions by foreign pathogens, they possess many barriers to prevent pathogens from coming into the body.

(03:27):

For example, one of the common features of mucosal tissues is that the outward facing parts of these tissues are protected by a mucus lining. Mucus acts as a formidable natural protective barrier and can prevent a therapy from reaching the underlying cells. So the DDX platform we developed at enGene was designed to overcome this barrier and deliver genetic material directly into cells lining these tissues where it can produce powerful therapeutic proteins locally. Our initial work focused on the gut and GI diseases. We explore whether our technology could deliver DNA or genetic cargo that produce potent anti-inflammatory proteins locally in the gut to treat inflammatory bowel disease. The GI tract is arguably one of the most challenging mucosal tissues to target because it presents many, many formidable barriers that other mucosal tissues in the body doesn’t have. In addition to having a thick mucus layer, the GI tract is in constant motion and contains ingested food, digestive enzymes, and a dense bacterial population. To overcome these challenges, we needed to develop a carrier for genetic cargo that would penetrate the mucus barrier while maintaining stability in the harsh GI environment.

(04:39):

I recall an interest in bladder cancer began in 2018. It happened following a chance conversation I had with my neighbor who is a urologist at the University of Montreal Hospital who specialized in treating bladder cancer. He helped me understand the significant unmet needs facing people with non-muscle invasive bladder cancer. He explained what a long journey it can be, how frequently it reoccurs, the significant number of surgeries called TURBT that patients often need to undergo, and how even periods of remission require regular surveillance with invasive cystoscopies. Furthermore, there’s a longstanding BCG shortage in the US which added to the problem. For some patients, the remaining options may be radical cystectomy, which as you can attest to, this is a major life changing surgery to remove the bladder and can be associated with significant complications. Now I remember that day quite vividly. I returned to the lab the next day and asked our team to evaluate whether the DDX platform could deliver genetic material to the bladder lining through intravesical administration, meaning delivering the drug product directly into the bladder through a catheter.

(05:45):

Now to make the long story short, early results were very encouraging and exceeded my expectations. Around that same time, the FDA in the US issued a guidance encouraging the development of innovative therapies for people with BCG unresponsive NMIBC, once again, highlighting the urgent need for additional treatment options. Before advancing the program into further development, we spoke with many urologists and people living with NMIBC. Their perspectives really help us design a therapy intended not only to have a meaningful clinical effect, but also to fit into patient’s life and the routine urology practice. That’s why we intentionally develop an immunotherapy with practical features such as straightforward preparations and handling, no need for ultra cold storage and administrations in a familiar outpatient setting. So that is a quick summary on how we ended up working in the bladder cancer space. I believe the lack of options for people with NMIBC was also an important factor that led to the founding of BCAN. So we are very pleased to partner with the organization and to share its goal of bringing more treatment options to people living with bladder cancer.

Rick Bangs (06:54):

Excellent. So what’s enGene’s mission or vision and how does it translate into action?

Anthony Cheung (07:01):

To put it simply, our mission at enGene is to develop medicines for urological cancers that are effective, well tolerated, and can ease the treatment burden for patients and providers. Our team has worked tirelessly to advance our lead investigational therapy, detalimogene voraplasmid into clinical development for NMIBC. We are encouraged by its potential and are working toward the possibility of submitting it for FDA review.

Rick Bangs (07:26):

And what’s unique about enGene?

Anthony Cheung (07:30):

So enGene specializes in delivering genetic material without using a virus. For those who aren’t too familiar with gene therapy or genetic medicines, every cell in your body contains DNA material that are made up of genes. These genes act like an instruction manual telling ourselves how to function. Disease can occur when an instruction is faulty, missing, or not working as it should. A gene therapy is designed to address the underlying cause of diseases by replacing a missing gene, correcting faulty instructions or adding a new gene that enables cells to produce a therapeutic protein. The biggest challenge in gene therapy is still delivery. That is how to get the genetic cargo into the right cells in sufficient amount while limiting exposure to healthy tissues. The genetic instructions may be powerful, but they cannot work unless they reach their intended destinations and enter the target cells. Many gene therapies engineer viruses as delivery vehicle for genetic cargos because viruses are naturally designed to enter cells, implant their own DNA and instruct cells to make more viruses. Now scientists very smartly remove these disease causing components and redesign the virus to carry therapeutic genetic cargoes.

(08:42):

Although this approach can be very effective, viral therapies are complex to manufacture at scale and they can require specialized storage, preparations, require special handling and administrations. Some also have even limitations related to the amount of genetic material that they can carry. Furthermore, viruses can trigger an immune response and inflammation, so preexisting immunity to that virus may prevent some patients from receiving treatment. Also, repeated dosing can be difficult because the immune systems may recognize a vector after the first dose. So historically, many viral-based gene medicines have been limited to use in rare genetically driven diseases. These challenges highlight the need for a safer, more precise and potentially repeatable non-viral delivery technologies. These practical requirements can also make it difficult to offer certain gene therapies outside large academic hospitals or highly specialized treatment centers, which can mean limited access for patients in certain geographies or the need to travel great distances to seek therapies.

(09:46):

Our DDX platform was designed to overcome several of these challenges. Its mucus penetrating properties help it to move through the protective mucus layer and deliver the genetic material to the cells lining organs such as the bladder. The platform is also designed with practical use in mind. It does not require  ultra cold storage, specialized containment, or post-treatment quarantine or urine bleaching procedures. Its manufacturing process is intended to be scalable, which could make genetic medicines more practical for diseases affecting larger patient populations. We describe this as helping to mainstream genetic medicines by making this innovative approach potentially more practical for healthcare providers and more accessible to patients.

Rick Bangs (10:28):

So I’m curious, what bladder cancer spaces do you play in?

Anthony Cheung (10:32):

Our lead investigational candidate detalimogene voraplasmid is currently being studied in people with high-risk NMIBC that has become unresponsive to BCG. This is an area with particularly significant unmet need. We also have some early work ongoing to help us understand what the detalimogene voraplasmid may have potential in additional subsets of NMIBC populations. We look forward to providing some updates here in the near future.

Rick Bangs (10:58):

And which patients in bladder cancer tumors are appropriate?

Anthony Cheung (11:02):

Our current priority is to evaluate detalimogene voraplasmid in people with high risk BCG unresponsive NMIBC, because these patients, as I said earlier, have urgent unmet needs for additional bladder preserving treatment options. Based on how detalimogene voraplasmid is designed to work, we believe it may eventually have potential in other types of NMIBC. Now obviously this possibility must be evaluated through carefully designed and conducted clinical trials.

Rick Bangs (11:28):

So what’s unique about detalimogene voraplasmid?

Anthony Cheung (11:32):

Detalimogene voraplasmid is designed to activate the immune systems locally within the bladder so that it can recognize and attack the bladder cancer cells. Delivering the therapy directly into the bladder allows the treatment to act where it’s needed most. This localized approach is intended to generate a strong immune response within the bladder while limiting exposure to the rest of the body. Detalimogene voraplasmid is made up of synthetic polymers, which wrap around the DNA cargo to form these very small particles to shuttle the DNA cargoes into cells. It uses enGene’s DDX platform rather than a modified virus to deliver its genetic payload to the bladder lining. Now I should point out that therapy remains investigational. Clinical studies are still continuing to evaluate its potential benefits and risks in patients.

Rick Bangs (12:18):

And how is it administered and how often?

Anthony Cheung (12:21):

In our clinical trials, detalimogene voraplasmid is stored in a vial that can be kept in regular fridge and freezers. When the patient is ready, the healthcare provider will prepare the drug product simply by adding water to the vial. It is then administered directly into the bladder through a catheter, a procedure known as intravesical administration. The therapy remains in the bladder for about one hour before patients empties the bladder. During the initial treatment phase, patients receive detalimogene voraplasmid four times in each 12 week treatment cycles. If a patient remains in complete response after fourth treatment cycle, which is a year’s time, they may move into a maintenance phase. During maintenance phase, treatment is administered only two times every three months or every quarter for up to two years.

Rick Bangs (13:06):

So how does it relate to BCG?

Anthony Cheung (13:08):

Detalimogene voraplasmid and BCG both activate the immune systems locally in the bladder to destroy cancer cells, but detalimogene voraplasmid is designed to engage the body’s immune system in ways that are distinct from those that are engaged by BCG. This is very important because we don’t want to engage the same pathways as BCG in patients that have become unresponsive to BCG. Because the effect is local, we can express very powerful natural factors in the bladder to stimulate the immune systems locally without causing unwanted systemic side effects. Furthermore, because we don’t have the same packaging limit like virus, these features allow us to carry more genes into cells in a single administration. In detalimogene voraplasmid, we’ve expressed three genes simultaneously in cells that lines the bladder wall, allowing us to properly engage multiple immune pathways in the bladder to generate the required anti-tumor immunity.

Rick Bangs (14:04):

What kind of work has enGene done with BCAN in the past or is planning to do in the future?

Anthony Cheung (14:10):

We have had the pleasure of attending BCAN’s think tank meeting for several years now, as well as sponsoring a number of walks organized by BCAN. This year we became a national sponsor of the Walks to End Bladder Cancer. We were honored to walk alongside patients and caregivers in Philadelphia, Nashville, Seattle, Chicago, San Francisco, Boston, St. Louis, and New York. Legend are clinical trials in patients with BCG unresponsive NMIBC is also a feature trial on the BCAN clinical trial dashboard. We’re also honored to be featured by BCAN’s Partner in Progress Initiative. Through our partnerships with BCAN, we have invited patients to visit our company and share the personal journeys of living with the disease. These events truly inspire our team and reinforce our purpose to deliver transformative therapies for patients and their families. Our organization is so impressed with the work BCAN has done so far and it has helped connect us with the broader community.

Rick Bangs (15:07):

So what do you see in the future for bladder cancer and what specifically is in your pipeline?

Anthony Cheung (15:12):

Well, we’re currently planning to initiate a submission of biologicals license application to the FDA for detalimogene voraplasmid for the treatment of high risk BCG unresponsive NMIBC with CIS with or without papillary disease before the end of the year. Again, one of the main goals we had when we designed detalimogene voraplasmid was to make the treatment that was really straightforward and that has the potential to lower burden on both practices and patients alike. We have also recently started a new cohort of patients in the Legend trial who have high risk BCG unresponsive NMIBC with CIS alone or CIS with papillary disease. Patients in this cohort receive a short five-minute bladder rinse with a surfactant called polidocanol. This is a product already approved by FDA for use as an agent in the treatment of varicose veins and other vascular disorders. Following polidocanol rinse, we administer detalimogene in the bladder through the same catheter. This surfactant bladder rinse helps to loosen up the stack of outer layer of cells in the bladder wall so that detalimogene voraplasmid can penetrate deeper into the bladder.

(16:20):

In our preclinical studies, we see a sizable increase in immune activation and we can achieve this in a shorter product dwell time in the bladder. So in our clinical studies, patient only required to have detalimogene voraplasmid stay in the bladder for 30 minutes instead of the 60 minutes which is being used right now. This means less time in the office for patients, less time they have to hold fluid in the bladder, which we understand can be difficult for some patients receiving intravesical therapy. We recently announced that we cleared the safety  run in portion of this study in patients, which means that none of the initial subset of patients enrolled experience any dose limiting toxicities, and we’re now expanding a number of trial sites across the US, Canada, Europe and Asia.

Rick Bangs (17:07):

Any final thoughts?

Anthony Cheung (17:08):

While there have been advances in care with new products becoming available, there’s still high unmet need for those with BCG unresponsive NMIBC. New treatment options have become available, but not every patient responds. And some patients who initially response will eventually see the cancer return. Our responsibility is to keep building on this progress by finding ways to make responses last longer, reduce the treatment burden for patient and simplify the treatment for urology practices. Anyone interested in learning more about enGene or what we discussed today, you can find more information directly on our website or via our Partner in Progress page on BCAN’s website.

Rick Bangs (17:58):

Anthony, I want to thank you for sharing enGene’s origin story and also the work you’re doing. We really appreciate your support for BCAN’s mission of creating better today’s and more tomorrows for bladder cancer patients and families.

Anthony Cheung (18:11):

Thank you,  Rick.

Rick Bangs (18:12):

If you’d like more information on bladder cancer, please visit the BCAN website, www.bcan.org. Anthony, can you tell us where listeners can learn more?

Anthony Cheung (18:24):

Well, to learn more about enGene, you can visit our website at www.enGene, that’s E-N-G-E-N-E.com. You can also find more about the work we’re doing on our Partners in Progress page and clinical trial dashboard on BCAN website.

Rick Bangs (18:39):

Excellent. Just a reminder, if you’d like more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today. Be sure to like, comment and subscribe to this podcast so we have your feedback. Thank you for listening and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Anthony.

Voice over (19:06):

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network or BCAN. BCAN works to increase public awareness about bladder cancer, advance bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.