All right. Good afternoon, everyone, and thank you for joining us at the 46th Annual Canaccord Genuity Growth Conference here in sunny Boston today. I'm John Newman. I'm one of the biotech analysts here at the firm. Very excited to have Candel with us today. We're joined by Dr. Francesca Barone, the Chief Scientific Officer. Welcome. First question, for anyone that's not familiar with Candel, and everyone should be, could you give us an overview of the company and specifically your lead asset, aglatimagene?
Thank you, John, and for having us here today. Candel Therapeutics is a biopharmaceutical company, developing off-the-shelf viral immunotherapies. These drugs are aimed at local delivery to achieve systemic immunization.
We have two clinical assets. One is aglatimagene besadenovec, or aglatimagene I would refer to that, and it was also called CAN-2409, so some-
of the literature still refer it as that. That is an off-the-shelf replication-defective adenovirus. It delivers a gene, thymidine kinase. It's given together with a prodrug, and the aim is basically to induce immunization, in situ immunization of the patients against the tumor or antigens. The main indication is localized prostate cancer. We had unveiled in 2024 a positive phase III randomized trial results, where aglatimagene demonstrated superiority around 30% to reduce disease-free survival risk for patients treated with aglatimagene as compared to patient treated with standard of care radiation. This asset is also in development for non-small cell lung cancer. We've completed a phase II study in this indication. We just very recently started recruitment for a new registrational, a potentially registrational phase III study called AURORA in non-small cell lung cancer patients with non-squamous disease that are non-responsive to first-line checkpoint inhibitors.
This is stage 4 disease.
This is the first clinical asset. We have another clinical asset, is a classical oncolytic virus. This is called linoserpaturev, previously known as CAN-3110. This is a classical oncolytic that is the first in class for its modification. It has been modified to selectively replicate within a tumor cell that express the nestin promoter.
This asset has been developed in brain cancer. Both for aglatimagene and for linoserpaturev, we had lots of interactions with the FDA. The phase III trial that I mentioned before for aglatimagene has been developed in prostate cancer under a SPA, Special Protocol Assessment. It received a Fast Track designation, as well as the RMAT designation, and the RMAT designation has been received by the FDA after study readout. With the phase III study readout data, we went to the FDA, and we got RMAT designation. That enables us a very strict communication with the FDA that is extremely useful since we are gearing up to file a BLA for aglatimagene by the end of the year.
Linoserpaturev also had Fast Track designation for the development in the brain cancer indication and Orphan Drug Designation as well.
Okay, great. Thank you. I believe Candel will be presenting additional prostate cancer data at ASTRO 2026 this September. I wonder if you could just describe in general what we might expect to see in that update, and how it might further support the positive data that you've already shown there.
Sure. First of all, as I mentioned before, we've achieved positive, the primary endpoint of the study under the SPA in 2024, where we demonstrated this ability of aglatimagene to delay recurrence of prostate cancer. As a part of the original primary endpoint of this trial, we had the possibility of obtaining biopsies from the patients, and the biopsies were pair biopsies, obviously baseline, and biopsies at two years post the end of radiation. This material is extremely interesting because it will enable us to investigate changes that have happened to the tumor microenvironment at the site of injection. What we've done, as part of our presentation at ASTRO, is an AI-enabled digital pathology analysis on the slides of the two-year post-treatment biopsies that will enable us to really see what changes aglatimagene makes on the top of radiation.
We're going to report the series of histological parameters. We had already disclosed at the time of data readout the ability of aglatimagene to induce an increased number of pathological complete response.
Meaning absence of the tumor at the two-year biopsy. We had 80% as compared to 63%. That was the data in the control arm. Now we're going to look at this a little bit more in details and using the digital pathology quantification of immune cell aggregates, differential distribution, a series of parameters like, for example, the closeness of the immune cell to the cancer cell. That is a very good readout of some of the mechanistic aspect that then underpin the clinical effect. It is important to say that obviously we had already proof of the mechanism of action of aglatimagene in other indication. We also had it in prostate cancer. We had a very early study in pre-prostatectomy, but this is going to be the first evidence of biological engagement of the immune system at the site of biopsies from the phase III trial.
Okay, great. As you mentioned just a moment ago, you've guided to a BLA submission in prostate cancer by the end of this year, 2026. Just curious how that process is progressing and just generally speaking, what your interactions with the agency have looked like.
The process is progressing very well. It's busy. We've been extremely busy, and particularly, I think these past two years have been extremely focused on execution of the elements that we needed to put in place in order to have a successful filing. This has been mainly focused on manufacturing. We had already, just before the study readout, to scale up the manufacturing for the product, for the production of the commercial product to the scale that we're going to use for the commercial product, that is the 200 liters. But there was still quite a bit to do. What was left for us to do was the PPQ campaign, and we can say that we've been extremely successful so far. We are around three quarters down to the PPQ campaign.
We are in close contact with the FDA through this process because one element that is extremely important for the filing is to have alignment on the comparability process. Obviously, in the clinical study, we had a non-commercial lot. It was a clinical lot that has gone into these patients. Now we have a new process. The process had to be changed to modernize some of the aspects related to it. We've been really busy in producing evidence that the two processes are comparable, and the product that comes out of the two processes is comparable, and this is what we've been doing. This is all under the umbrella of the RMAT designation that enables us to have a frequent meeting with the FDA. Every meeting is a type B meeting.
We have a 60-day turnaround, so we had the possibility to check with them what was our plan for comparability. Very recently, we had a meeting in which we aligned on the comparability protocol that will be executed at the end of the PPQ campaign. The other element that has been important for this, and let's fill out some of the activities for the past two years, is the stability. The product that comes from the new process has to be put on stability to create what is going to be the indication for the shelf life of the product at the time of launch. We have product on stability now. We are generating this data, and we're putting together the Module 3, all gearing up at the moment for the timeline of submission by the end of the year.
Mm-hmm. Okay, great. Just curious, what type of feedback have you received from key opinion leader physicians on the prostate cancer that you have generated thus far? How clinically meaningful do you think, and do they think, is the 30% reduction in disease recurrence that you have seen?
Yeah. This is a part of a very exciting activity that we are taking at the moment. We are taking these two years really to help us to create this relationship with future prescribers. We started all the activities related to medical affairs and commercialization, among which, obviously, gearing up, getting feedback on our drug. The feedback has been encouraging, extremely encouraging. There is a lot of excitement. This will be the first drug in this space in more than 20 years. The alternative in this space is really radiotherapy or radical prostatectomy. There is excitement for aglatimagene. When we discussed the data, the disease-free survival, the physician found this to be a meaningful improvement, in particular because the next line of therapy for patients that failed radiotherapy or failed radical prostatectomy is ADT. We are particularly selective of the patient.
Obviously, with radiotherapy. There is a rate of recurrence in this patient that is 30% for the intermediate risk population and up to 50% in the high risk. It is a reality. For this patient, the next line is ADT. ADT is a drug that works, but it is a drug that nobody really likes. Physicians do not like to prescribe it, neither patients like to take it because of the complication of the side effects related to this drug. There is an effect on the quality of life, and it comes with a series of morbidities that is sometimes intolerable for the patient. Patients tend to be against the prescription, but also tend to have very poor adherence to that. There is excitement on that respect, and the physician finds this a meaningful improvement.
On top of this, the data that we presented in the spring to AUA, in which we have reported long-term outcomes in additional exploratory, purely clinical endpoint, has been extremely exciting for the physician. What we have reported at AUA is that DFS improvement translates, as we have predicted, actually, in longer time to metastasis, longer time to biochemical failure, a longer time to new anticancer treatment. This is a validation of our hypothesis that the DFS endpoint, and in particular, the data that we were obtaining from the two-year biopsies, were going to be correlating with long-term improvement in these patients. This is what we see. We see a clear separation of the curve. Patients treated with aglatimagene have got a longer time to metastasis, less incidence of metastatic disease, and longer time to this next line of therapy, and this is clinically meaningful.
Mm-hmm. Okay, great. Thank you. A follow-up on a point you just made regarding androgen deprivation therapy. Aglatimagene has demonstrated a benefit regardless of whether patients have received androgen deprivation therapy or have not received it. Again, how important is it to reduce or avoid ADT from the physician perspective, and how important do you think the flexibility is there you can give your product whether or not they've received it?
I think it's extremely important. I was just coming back from one of the PCF, the Prostate Cancer Foundation conferences, so this was a Delphi consensus process, a metastatic disease. I think there were a lot of discussions in the community in the sense that the community of physicians want to really identify the patient that will benefit from ADT because of that very unfavorable benefit to risk associated with the use of ADT. Unfortunately, ADT is a drug that works. We have plenty of evidence in randomized clinical trials, but patients don't like to take ADT.
We had some of the physician that gave us feedback and said, "Patient don't feel men from the day after they start ADT." On the top of it, obviously, there are effects on the musculature, there are effect on bone loss and so on. There are the cardiovascular risk. There are many patient that cannot take ADT, so they cannot even take the advantage of that despite the side effect. So the possibility of delaying, and in total reduce the number of years so that this patient will have ADT is absolutely a goal. The curative intent that you have when you treat a patient with localized prostate cancer shouldn't have to be paid with the price of ADT. That's why some of the patient want to get a radical prostatectomy.
They want to avoid the ADT because they think that the risk associated with getting ADT if they get radiotherapy is higher, right? So the possibility of getting a drug like aglatimagene that is only injected 3x and that's it, and then you have this long-lasting benefit definitely outweighs the issue with the ADT. So we are very aligned with this community of physicians that don't want to prescribe ADT and with the patients that don't want to take ADT. This is what we hear also when we discuss with patient. We've been starting all these activities also to understand from their point of view what they feel about this therapy. So I think that's one of our stronger theme. You're right, the benefit of aglatimagene is independent of the use of ADT.
Despite the study was not really powered to look at subgroups, the directionality of the response there is very clear.
Okay, great. How are you thinking about the commercial opportunity in localized prostate cancer? Do you think a therapy like aglatimagene might encourage more patients to opt for radiotherapy rather than surgery?
You're not the first person that tell us that. First of all, we designed the study to really target the population of patients that are treated with radiotherapy. This is a very large population. There are 65,000 patients per year get diagnosed with localized prostate cancer and will undergo radiotherapy, will choose radiotherapy. This is 40%, roughly, of the overall population of patient, intermediate, high risk patient with localized prostate cancer that get diagnosed. This is a 60/40 split. If we look just specifically at this population, we are thinking about a commercial opportunity that goes between $10 billion - $16 billion. It's really high up in the projection that we have. Now, if we think about the way in which some of the physician have feedback us about this therapy, we've always thought, okay, it's going to be three opportunities.
You're going to either go to radical prostatectomy or radiotherapy, or radiotherapy plus aglatimagene. Actually, the physician look back at us and say, "Well, no. We see this as a two possibilities, radical prostatectomy or radiotherapy plus aglatimagene," because really, they see the value of that. Now, can this translate in the future in what you were saying that more and more patient will choose radiotherapy to avoid that? It is a possibility. It's not, at the moment, embedded in our forecast, so we've been extremely conservative. But yes, it is a possibility because some patients decide to undergo radical prostatectomy because they don't want to incur the risk of having to use ADT. So if we decrease that and improve the ability of radiotherapy to be efficacious in diminishing the possibility of recurrence, there is that possibility, and we heard that also from some physicians.
Mm-hmm. Okay, great. Shifting over to non-small cell lung cancer, you recently initiated a registrational study here. Very exciting. Could you walk us through the clinical design there?
Sure. We had a very positive end of phase II trial meeting with the FDA, and we brought them a clinical study that was focused specifically in the non-squamous population of patients with stage 4 disease that were non-responsive to ICI. These patients were either previously responsive or presenting as after the first-line treatment, and they were coming after 12 weeks. So classical study design according to the NCCN guidelines. The FDA agreed to this study design. So what we are planning to do is to recruit 500 patients. It is going to be a one-to-one randomization. The control arm is very clear, docetaxel, this is the anchorage in the treatment, as they define it, in the treatment on non-small cell lung cancer. The endpoint is median overall survival. The median overall survival for docetaxel is around 12 months.
It has been confirmed over and over again in phase II and phase III studies. None of the current medicine in development have beat the 12 months. So we have been finding ourself really the possibility to power the study using the data from our phase II study. So what we have done is that we have looked specifically at the non-squamous histology, those were the patients that responded better to aglatimagene. In these patients, we have achieved a median overall survival of 24.5 months, but we have been very conservative. We looked at the intent to treat population in the non-squamous subpopulation, and we have seen that even in this, we achieve a median overall survival of 17 months, so we largely exceed the 12 months. We think we can even improve that. Why? Because we know now that if we inject a patient specifically in the thorax, with aglatimagene, we improve that survival.
The other aspect is that we have been better at understanding how our drug works. So we knew that we had some patients in which we had pseudoprogression, and at the six-week scan, some of the physicians were feeling a little bit nervous and taking the patient off study. So we had some patients that did not even get the second injection of aglatimagene. We really think that the course of two injections, when you have a primer and a booster, is necessary in order to have the full effect. So we think that we can even improve that. So we have been conservative in our estimate for the study design.
Mm-hmm. Okay, great. Could you talk about how aglatimagene is administered in lung cancer? Is the goal to inject every accessible lesion, or is there evidence that the treatment could generate a broader systemic immune response, such that you may not have to inject every single lesion that the patient has?
Absolutely. In non-small cell lung cancer, first of all, we only give two administration of aglatimagene, so two injections. You don't need to repeat the injection more than two times because you really have this effect of primer booster that I was alluding to before, where you inject either the same lesion or two different lesions, and you achieve a long-lasting process of in situ immunization. What is important is that we've already described changes in the tumor microenvironment, activation of the immune cell at the site of injection. We proved that through longitudinal biopsies. But we've also proved a clear systemic effect. We've reported biomarker data in the phase II study where we show an activation of the T cells, generation of a memory response with activation both of the CD8 and the CD4 compartment, activation of the B cell response.
Most importantly, this translating a clear clinical effect in non-injected lesion. We had regression of non-injected lesions, and we reported that as a abscopal effect, looking both at overall responses or 5%, including only patient that had more than 5% shrinkage of non-injected lesions. We reached that on around 60%- 70% of the patients. So if you consider the totality or only the more than 5%. Really we have evidence of a systemic response. You don't need to continue giving this over and over again because it's the ultimate medicine here are the T cell that get educated to recognize the tumor, so they can go from the tumor microenvironment, patrol around and recognize metastatic sites. This is clearly evident both from the biomarker and from the clinical data.
Mm-hmm. Okay, great. Thank you. I want to talk a bit about recurrent glioblastoma for CAN-3110 here for a moment. You have an ongoing program here, in recurrent glioblastoma. Could you remind us again of mechanism of action?
Yes. This is different from aglatimagene. This is CAN-3110, or linoserpaturev. It has got its new generic name. This is a classical oncolytic virus, but it is a first in class for the modification that have been made to this virus. The mechanism of action is related to this ability of the virus both to replicate and kill tumor cells. This is directly injected in this case, and the indication is recurrent high-grade glioma, so it gets injected through burr holes into the tumor directly. But it is also capable for the modification that have been made to the virus itself to induce a very strong immune response, both locally, that is almost unheard of in the space of glioma that is classically super cold tumor microenvironment, but also in the systemic circulation.
The data of this have been published in "Science," the original description of this virus, and then in "Nature," and more recently in "Science Translational Medicine" and in "Cell." We have clear evidence of activation of the immune system. The modification is that this is a first in class because it is the only virus in which the gene responsible for replication had been deleted, but reinserted under the nestin promoter. That really enables this capability of the virus to specifically replicate and kill tumor cells whilst activating the immune response. We are really excited about the data that we generated in this indication. We had achieved a median overall survival of 12 months after single injection. We are now going to disclose at the end of the year new data on the multiple injection cohort, and also follow up on the patient that had long survival.
We have reported already that a couple of the patients in our phase I trial survived more than 49 months, 50 months. So it is quite unheard of in the space of recurrent glioma.
Mm-hmm. Excellent. Well, it looks like we are out of time. I wanted to thank you, Francesca, for joining us today. Also, thank you to the Candel team. Thank you to the investors here in the room in Boston, and everyone on the webcast.
Thank you.