Candel Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah, absolutely. Candel Therapeutics develops viral immunotherapies for very difficult to treat solid tumors. We have two investigational medicines in the clinic. The first is called aglatimogen besadenovec. I will call it aglatimogen for short, and we are preparing for BLA submission. We have achieved a primary endpoint in a pivotal placebo-controlled phase III clinical trial in newly diagnosed localized prostate cancer patients who seek curative treatment through radiotherapy, and I guess we will come back to that. We also have positive data for aglatimogen in non-small cell lung cancer. Recently, we announced that we have started our first global phase III clinical trial in therapy-resistant non-squamous, non-small cell lung cancer patients with progression despite immune checkpoint inhibitors, pembrolizumab, KEYTRUDA, and cisplatin-based chemotherapy.

These patients have a very poor prognosis, and we have very encouraging phase II-A clinical data that are currently under review at the scientific journal and that are really the basis for the design of this phase III study. We also have positive data in borderline resectable pancreatic cancer. For the same asset, we have paused this program because we cannot do everything at the same time. The data were very encouraging. We got also Fast Track designation, Orphan Drug Designation, and it reinforces the notion that this is a pan-solid tumor off-the-shelf therapy that induces an individualized anti-tumor immune response specific for the patient's own tumor. That is the first asset, and then the second is called linoserpaturev. Actually, it is equally exciting, but it is in an earlier stage of development.

We call it phase I-B, but you could easily call it phase II-A because we have now dosed 62 patients with recurrent glioblastoma brain cancer. These patients are probably the most difficult to treat, and we have very encouraging data that we published in Nature and in Science Translational Medicine. This has also the potential to become a pipeline in a product because there is a possibility to not only go into recurrent glioblastoma, which is a huge unmet need and commercial opportunity in itself if you have something that seems to work, but we could also expand into indications based on other indications based on the biomarker called Nestin. That is where I will pause.

Of course. Most important, we are preparing for BLA submission.

Yeah. We have conducted a study in 745 patients with intermediate or high-risk prostate cancer who elected to undergo external beam radiotherapy, EBRT, with curative intent. These patients get radiotherapy on the prostate, and the goal is to eradicate the tumor. The problem is that despite this radical treatment, there is a chance of recurrence of at least 30%. It is quite high. We try to increase the proportion of patients that will achieve their goal of living free from evidence of recurrence with all the complications over time, like symptoms due to local progression of the disease, symptoms due to metastatic disease over time, the toxicity, and the side effects of long-term cell-rich anti-cancer therapies, especially long-term androgen deprivation therapy, ADT, basically chemical castration, which has a very negative impact on quality of life in at least two-third of the patients. Patients hate it. That is what we try to avoid.

We designed a clinical trial in agreement with the FDA, conducted under a Special Protocol Assessment, SPA. That basically means that there was basic alignment about what the trial looked like, including the primary endpoint, disease-free survival, DFS, which is the right endpoint if you treat patients with prostate cancer with curative intent. It is an event-driven endpoint, and we have achieved that with a hazard ratio of 0.7, that means 30% improvement in disease-free survival. That includes all events, including death, completely unrelated to prostate cancer. Think of an accident, a car accident, or somebody fell off a ladder and died.

Or a heart attack or a stroke. All of that was included despite that, because you dilute the signal by doing this. We still achieved this with statistical significance. What follows is that the key secondary endpoint was prostate cancer-specific disease-free survival. That is when you exclude death not related to prostate cancer.

and then the results look even better. We have achieved that, convincingly supported by other secondary and exploratory endpoints. Very importantly, we did a 2-year biopsy, which is not part of standard of care, but this is a research tool. It is the most objective way to detect cancer cells and also the most sensitive way. We observed a pathological complete response at 2 years in the patients who had received aglatimogen in 80% of the patients, compared to 63% in the control group who only received radiotherapy. Again, statistically significant. Why does that matter? Because we know based on the literature that this is predictive of subsequent clinical outcomes, and that is what we have shown, and we can discuss that further.

Yeah. It is a simple procedure, actually, to inject aglatimagene into the prostate. Non-clinicians may find needles scary, but actually it is super simple. There is no place in the body that cannot be easily reached with a needle. The whole procedure takes 15 to 20 minutes in an outpatient clinic, is often better tolerated than a standard of care diagnostic prostate biopsy, which is a completely routine procedure. So what we do is the urologist or the radiation oncologist, they are the treating physicians. I think it is important to understand this. They are used to manipulate the prostate. They put needles or spacers into prostates every day. This is a simpler procedure than a standard of care biopsy.

They inject 0.5 mil in each of the four quadrants of the prostate in an outpatient procedure, and that leads to a diffuse distribution of aglatimagene in the whole prostate. Then we give the patient a tablet called valacyclovir for 2 weeks- and that leads to massive immunogenic cell death.