Candel Therapeutics Inc R&D Event Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : So let's just start out with a big high-level question, which is, what makes an immunotherapy target good? And two subquestions behind that. First of all, why do some IO targets that seem very promising in research labs end up having such different real world clinical impact and value? And secondly, how does the industry get better at predicting which ones will have the best clinical outcomes? Jim, maybe we can start with you, and then move to Pam and to Carl, please. Thank you. James Allison - James P. Allison Institute, University of Texas MD Anderson Cancer Center - Regental Professor and Chair of Immunology, and Founding Director of Scientific Programs Yeah, I think that the best targets are those that when you either give a either block them or give an agonist signal results in induction of your own immune cells so that you have long living, immunity after the whatever drug you used, is gone. I think that should be the goal of all the immunotherapies. And I think that, the reason that we're off sometimes is that things change when you give something and treatments are based on baseline biopsy, not on on-treatment biopsies, and I think it'd be useful to, really get an idea of what the changes are downstream and get some idea of what's, what, how the immune system has changed in the local environment of the tumor. We know what the good response looks like. That can give you not only ideas, by knowing what's happened, you can not only get an idea of what you've done, but also what you may be missing, because we know what a successful, therapy looks like at this point. I would suggest that. LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 05, 2025 / 4:00PM, CADL.OQ - Candel Therapeutics Inc R&D Event Or we're getting to the next question about building an atlas of all the spatialomics data that's getting to be available from different treatment groups would be a very valuable resource for companies to have, so they know a little bit more than just what they see on a TCGA analysis to predict their outcome because that falls way short for many reasons of being a predictor. So it's just inducing long-term immunity, that should be the goal.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : Carl, what are your thoughts? Carl June - Center for Cellular Immunotherapies and Parker Institute for Cancer Therapy, Perelman School of Medicine, University of Pennsylvania - Professor in Immunotherapy and Director I think you got -- so, my point of view would be my interest, how would you combine cell therapies with checkpoint therapies, oncolytic viruses, and so in the case of cell therapies, where we've had a lot of success has been when there's lineage dependent targets, and we don't have that in solid tumors where we really need to go. And so I think one emerging issue is being able to have targets that are drivers in the tumor. One huge advance now is potentially targeting things like mutated KRAS. LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 05, 2025 / 4:00PM, CADL.OQ - Candel Therapeutics Inc R&D Event And we'll have less escape, but I think we're going to need to have, as Jim said, the ability to trigger an immune response against. The total tumor, and that requires the tumor mutational burden, but we need to start the fire and then need to have it be catalytic to broaden out.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : Carl, is your answer? Carl June - Center for Cellular Immunotherapies and Parker Institute for Cancer Therapy, Perelman School of Medicine, University of Pennsylvania - Professor in Immunotherapy and Director I mean, yeah, I agree with that. I think we need to understand more about the stroma and how, what the immunosuppressive mechanisms are in a given tumor, and the huge innovation there is what Jim mentioned, spatial biology. If we have, huge databases on that, it's going to really accelerate the entire field, and right now we're not having cross learning really, I don't think enough between different trials and what the tumor microenvironments were and then understanding the escape and resistance mechanisms. So that would be something that everyone would benefit from if we had an atlas of spatial biology of various tumor microenvironments.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : Right. Well, you all pre-answered my next question, which is fine. I was going to ask about the combo approaches, with non IO based therapies and which tend to be most effective. You mentioned a lot of things, including the oncolytic viruses, T cell therapies, The RNA vaccines, LNPs, in vivo LNPs, in vivo cars. Maybe just spend a little bit of time talking about, which of those may seem more promising in combination with IO. Do they all have to be tried? Do they all have different advantages or different disadvantages? If you could just expand on that line of thinking, please. Padmanee Sharma - James P. Allison Institute, University of Texas MD Anderson Cancer Center - Professor of Genitourinary Medical Oncology and Immunology, and Director of Scientific Programs I do think that they're all going to have to be tried in some ways, right? Because, although all of these look promising in pre-clinical settings, I think we need the clinical data, at least 10 or 20 patients. I'm a big proponent of saying 10 or 20 patients to test the concept, collect all the samples from those patients to understand whether you really targeted the appropriate. Biologic pathways and immunologic pathways to get outcomes, for our patients that needs to be looked at. So I think we can do small trials where we ask the question, did this combination effectively change the immune response in a way that we would like to see and did we see any clinical outcomes that's a signal for then expanding that into larger numbers of patients to look at. So I think those are the things that, will need to be done. LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 05, 2025 / 4:00PM, CADL.OQ - Candel Therapeutics Inc R&D Event I don't know that we can haphazardly just choose which one will go just based on the pre-clinical data, because I have to say the pre-clinical data is looking very good in many of these different combinations. It's just whether or not they'll translate in the clinic. The one other thing I want to highlight is that let's not forget that we have our, known, treatments in cancer, right? Surgery, radiation therapy, chemotherapy. These are known pillars that work well in cancer patients, and how do we combine immunotherapy with these become very important. So recently we were able to show that surgery, for example, even in the metastatic disease setting, if you take out a single lesion, usually we wouldn't do that because surgeons don't like to take out a single lesion and leave a lot of other metastatic lesions around, because what's the point in removing one lesion, but what we're showing is that by removing a single lesion, you are changing the immune response and the antigen load and so. You can get benefit then with surgery and immune checkpoint therapy. And so we showed this some of this data in a pilot study, and I think this needs to now move on to larger studies. So I do think combinations that can get us in that direction, how do we combine these different things, and why combine them? What's the mechanism behind combining them becomes important.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : Okay. So you mentioned combos and being able to test multiple things at once. Would that suggest, that buy specifics or even try specifics, there's some of these tri-specific T cell engagers out there. Does, do those become more interesting because you can test multiple things at once and sort of get around some of these, operational challenges, as you've alluded to? Padmanee Sharma - James P. Allison Institute, University of Texas MD Anderson Cancer Center - Professor of Genitourinary Medical Oncology and Immunology, and Director of Scientific Programs I think one of the issues with, trying to put everything all together as in tri-specific or bi-specific, right, we don't understand sometimes all of the steric interferences that may come with having these agents combined rather than giving them singly. Also, we don't have all of the biology that we understand from the single agent alone, much less coming in with by specific and tri-specific, right? Don't know how the human immune response is changing in response to a single agent. We may not even know what the target and ligand receptor ligand pairs are, you mentioned tigge, for example, and everyone is disappointed about the digit failures that we've seen, but I mean, I think the biology of tigid and how digit, what's the receptor ligand paired that's most important in that digid pathway and what's the signaling downstream is still unknown. So I think sometimes we move so quickly to buy specific, try specifics without understanding some of the biology. Behind a single agent by itself that that may also hamper us as we get into clinic, but again, it's a matter of trial and the patients and then seeing what that data points to before we can make next decisions. So I do think, those are things we have to look at. I'm very convinced that combination therapies are going to be the way to move forward and obviously we all have seen data where good combinations can be. Meaningful in patients, and again in order to test those combinations, I think small 10 or 20 patient trials put together the combination that you see that the biology made sense in a pre-clinical data set, take that into 10 or 20 patients and make sure that the biology replicates from that pre-clinical data set into human data and then move that forward into larger trials and I think those are the those are the pieces that we have to put in place.

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : All right. Well, on that forward-looking and optimistic thought, Pam, thank you very much, Jim, Carl, thank you all very much for doing this. And I will turn it back to Paul Peter to continue the session. PRESENTATION

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : Great. Thank you very much, Paul Peter. I was curious about some market dynamics. I think in the past, you've talked about how, the market was split approximately fifty-fifty radiotherapy and prostatectomy. And given your data and potential, changes to practice, paradigms, would you expect the market to shift to a greater use of radiotherapy?

Question: Yigal Nochomovitz - Citi Infrastructure Investments LLC - Analyst : And then you mentioned NCCN guidelines a little bit a second ago. In this situation, you've had the phase 3 data for a while, and given the manufacturing timelines, you have a lot of, a lot of time to work on getting those guidelines. Is there any possibility that you could get those, even before the launch, or that's not realistic? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 05, 2025 / 4:00PM, CADL.OQ - Candel Therapeutics Inc R&D Event