Agenus Inc. (AGEN) Earnings Call Transcript & Summary

Good evening, everyone, and thank you for joining us today. My name is Stefanie Nacar, and I'm Chief Communications Officer here at Agenus, and welcome to our September Stakeholder Webcast. Joining me today are Garo Armen, our Chairman and Chief Executive Officer; Dr. Steven O'Day, our Chief Medical Officer; and we'll also hear from Dr. Benjamin Schachter of the Dana-Farber Cancer Institute. Our discussion today will focus on the progress that we've made since our July webcast, including implementation of the ROBBIN Phase III neoadjuvant program, continued physician interest in the access to BOT+BAL and recent clinical and investigator-led activity that is helping inform the acceleration of BOT+BAL into the earlier disease settings. Following the prepared discussion, Agenus leadership, including Dr. O'Day as well as Robin Taylor, Chief Commercial Officer, will join Garo for a live Q&A. Questions may be submitted at any time during the webcast using the Q&A function of the Zoom event below. Before we begin, just a brief reminder that today's discussion includes forward-looking statements, so please be sure to refer to our SEC filings for additional details also available on our website. With that, I'm pleased to introduce our Founder, Chairman and CEO, Garo Armen.

Thank you very much, Stefanie, and thank you, everyone, for joining us today. When we had this session back in July, we spoke about the financing that was announced then. And we also spoke about the strategic shift into the neoadjuvant setting in terms of our approval strategy. And at that time, of course, the concern was before that announcement, the concern was our path forward. I think very few people were questioning the high activity of our product or combination, but people were more interested in how were we going to take this to the finish line. And certainly, the financing played a major role in addressing that question. And since then, our stock has reacted favorably by all standards. And we believe that some of the critically important risks associated with financing the company's future were at least removed for the time being. Now we're not going to repeat that discussion today, but what matters now, and you're going to hear about this from Dr. O'Day and if there are any questions, of course, Dr. Taylor, how are we doing since then? What are we doing to execute towards that strategic goal of initiating and completing our neoadjuvant trial. Now over the last few weeks, there were 2 important bodies of bio clinical evidence that moved into peer-reviewed journals for clinical cancer research, which is the prestigious journal of the American Association of Cancer Research. And the longer-term Phase Ib study, which is in the refractory MSS metastatic colorectal setting, published shows longer-term follow-up and durability, and you'll hear about this also from Dr. O'Day, durability of responses in patients that respond. These are, of course, important studies for us. The next one is the NEST neoadjuvant study, and that also talked about how we haven't had any recurrences since the study began. Now we're also seeing increased investigator interest in studying BOT+BAL in the earlier disease setting. Of course, shifting to the neoadjuvant setting for our approval strategy helped. But we're seeing also additional investigator sponsored proposals and studies for neoadjuvant. You're going to hear more about them, including the RECTIFY-1 study led by Dr. Ben Schlechter, and Dr. Schlechter is going to be joining us in just a bit. We interviewed him 2 days ago because of his patient schedule, and we're delighted that he had the time to discuss some very important points with us. Now all of this is important because it gives patients the opportunity to be able to benefit from BOT+BAL. It doesn't change our course with the ROBBIN study. That is the strategic focus of the company, both for a financial allocation of resources and people allocation of resources. But it also reflects the broader clinical interest in asking what BOT+BAL may do before surgery and creates additional clinical trial access to patients. At the same time, physician interest in accessing BOT+BAL outside of clinical trials also continues. We've had geographic reach and our access programs have expanded. We're seeing repeat interest coming from physicians. As you know, we have the French AAC program. And then outside of that, we have the paid name patient program, and those requests are coming in, and that demand is growing. Now at Agenus, our development priority, as I said before, remains very clearly advancing ROBBIN, our neoadjuvant CRC study in the colon cancer setting forward. Steven will update you on how this program is moving forward. We've had some very exciting initial interactions. Well, they're not initial interactions anymore because I think we've covered the majority of the sites that will participate in this trial already. We'll also discuss what we're seeing through our access programs in addition to what I mentioned before. So as I said, you'll hear from Ben Schlechter, Dr. Ben Schlechter of Dana-Farber, why the timing of immunotherapy may matter in colorectal cancer for the first time, why MSS disease has historically resisted first-generation immunotherapy, while we're seeing responses in bowel patients even in the late-stage setting where there's really no treatment options left for them. So that's where I'd like to stop and turn this over to Stefanie to take the program forward.

Thank you so much, Garo. And with that, Steven, let's actually start on a conversation here together and kind of take -- take up where Garo left off. So when we announced the ROBBIN Phase III neoadjuvant study back in July, we had done a lot of work, you in particular, to define the study, the component that we received FDA feedback on, on those key elements of this program to move forward and really establish the resources to move forward, including the financing that Garo just alluded to. So I know it's only been about 2 months, but there's obviously been a tremendous amount of work and activity from you and the team and the organization towards opening up this global study. Can you share a little bit about what has changed operationally since July and where the team is focused today?

Well, thank you, Garo and Stefanie. And boy, has it been a busy couple of months. really unprecedented in my experience with excitement and enthusiasm. We obviously have a deep network of thought leaders and principal investigators around this very mature BOT-BAL program. But in July, we were focusing primarily on the design of BRAIN, aligning with the FDA rationale for moving BOT+BAL into the neoadjuvant setting, a very important pivot that really optimizes the signal that we're getting with BOT+BAL with an intact tumor and draining primary lymph nodes. But since then, our focus in the last 2 months has been really increasingly and almost exclusively a shift to implementation and start-up of this very important ROBBIN global study. This includes building and continuing to expand our global investigator and site network advancing the regulatory and ethics work required in the countries where we intend to conduct the study, establishing pathology and translational infrastructure and aligning our clinical, operational and drug supply functions around the study initiation. There are a lot of individual work streams in the company right now involved with opening this global Phase III trial, and we are moving in parallel with rapidity and efficiency and excellence, and our goal continues to be enrolling the first patient in quarter 1, 2027.

Well, that seems to be a huge undertaking, but very confident, particularly even you are no novice to clinical studies being an investigator yourself before coming here to Agenus. So give us a little bit of a sense of the scale of that effort, Steven. How large of the clinical network are you building for Robin? And what can you tell us about the geographic footprint, particularly? I know we haven't shared much about that as of yet.

So this is a Phase III global trial of approximately 850 patients. It will involve North America, Europe, South America and Asia. We are extremely mindful, and I am in control with my team of selecting high-volume and high-quality sites. And this is particularly important with a neoadjuvant study. It's really very different than studies in the late-stage metastatic setting. It's important these sites see the patients, which are high-risk Stage II and III cancer. As you know, there's an epidemic worldwide. So these cancers are prevalent, particularly in the MS stable, 90% of all colon cancer. And most importantly, though, that neoadjuvant studies require multidisciplinary teams to identify these patients, become aligned around neoadjuvant treatment. Now this involves a medical oncologist clearly. But what's different here is we need alignment and leadership from our surgical colleagues but also our radiology colleagues, our pathology colleagues, our gastroenterologists and our research teams. And this is no small chore. But our deep networks, my experience across 30 years in the clinic and networking with KOLs around the world has definitely been very helpful. But the data itself is what is most helpful and is really exciting people to participate in the trial. Most of the sites are major academic centers, but we're also selecting high-performing, high-quality community-based centers and networks as long as they're integrated in terms of the multidisciplinary neoadjuvant setting. Interacting with medical oncologists alone is simply not enough. In order to be successful, we need to align and the enthusiasm from these multiple stakeholders.

Question, so you just talked a little bit about the broad scope and your personal involvement in site selection as well, likely because of all of the relationships that are out there and the experience. Are these sites and some of the investigators primarily investigators that are already familiar with BOT+BAL? Or are you seeing that Robin is also bringing in new investigators and institutions that don't have prior involvement or haven't really been connected much more broadly with the program previously?

So it's a combination. But I will say with over almost more than 1,200 patients treated in our Agenus-sponsored trials as well as our investigator-initiated trials across the globe, we have an extensive network of investigators and thought leaders -- but what's interesting is there's also thought leaders and investigators that have been more concentrated in the neoadjuvant space, and we're leveraging this. So we are bringing in additional new thought leaders and investigators with a particular experience in neoadjuvant settings. And as you know, in MSI colon cancer, there is now an evolving experience in this neoadjuvant setting for GI oncologists. And so we're really piggybacking and really driving that experience. And so the short answer is it's a combination of our existing, but a whole new group of investigators are seeing this data, have done neoadjuvant trials and want into this large global trial.

Yes. I think that we'll get to this a little bit later, but even more so recently, a lot more new adjuvant investigator-sponsored studies are launching as well. In our July webcast, right, we had Dr. Pashonkosi with the NES 3 study and Dr. Benjamin Schachter today, who started the RECTIFY-1 study at Dana-Farber. And then there's other neoadjuvant studies as well going on at MSK and then also in the Netherlands. So a lot of interest in the neoadjuvant setting, which I'm sure is a part of a lot of the excitement too, around ROBBIN. Earlier, just getting back to something that you had mentioned though, Steven, about the multidisciplinary nature of these sites. You started to allude to this a little bit, but what is operationally a bit different about a neoadjuvant study like ROBBIN compared to a traditional later line study? And why is that experience so important as we think about appropriately and efficiently getting ROI off and opening and enrolling and that consistency that you alluded to earlier across all these different global sites. Can you talk a little bit about that?

Yes. So let me build on -- I've obviously talked about the multidisciplinary alignment that's really critical. What people are very excited about is that this could be a paradigm shifting study that will not only reduce recurrences and improve survival, but deescalate chemotherapy in this very early-stage setting. So that's really important. But there are other issues here. In addition to aligning the medical team, there's health -- you're dealing with patients that are newly diagnosed. They're in health care systems expecting potential standard of care surgery and adjuvant chemo. Patients want more than that. Doctors want more than that. And ROBBIN trial inserts a defined treatment period before the surgery so that part of the process must fit within this established clinical pathway. I think patients are more than willing to delay their surgery a short period of time, given the data that we've shown that none of these patients have progressed during this period of time and the opportunity to improve survival and reduce chemo is a win-win for doctors, surgeons, medical oncologists and everyone involved. So -- but you do have to identify the patient, you have to stage them. You have to identify their MS status, which is now routinely done in all colon cancer. And then you move forward in a relatively short interval and you need the teams to be ready and teed up. And that's what we're spending a lot of time talking to the teams and really being sure that they're set up for success. Success will require that patients be present, but also that the teams really function at a high level to get the treatment in and the surgery and the adjuvant therapy.

Yes. So that's a lot of coordination and across the different parties at the different sites. And you also mentioned pathology and the importance of that particular expertise within the multidisciplinary function because it's also a very important feature of how we're going to begin learning about the impact of BOT-BAL within the ROBBIN study. Can you share with us a little bit about what needs to be in place to ensure that the pathologic response, the assessments, right? We know that this is a huge milestone for us are consistent and rigorous across how it's going to be assessed across this large global study.

Yes. So I think what's important is we're not starting from scratch here. The neoadjuvant setting with immune therapy has been established in melanoma. It's also prevalent in breast cancer now and lung cancer in terms of neoadjuvant perioperative -- so things are in place in terms of leveraging that history. But what's really exciting for everyone is that even though time to distant recurrence or metastasis in the cancer is the primary endpoint of the study, we will get an early readout after the first 8 weeks or so of treatment on the depth of this pathologic response. And more important than ever in immune-mediated therapy, more so than chemotherapy or targeted therapy, the depth of these responses are so highly predictive of eventual metastasis. So we will be looking at complete and near complete responses, and that will give us a lot of confidence as we go through, and this will be centrally reviewed by the trial that we are consistent with our Phase II data and highly set up to succeed in terms of the primary endpoint of the study. Now this does require that we coordinate this, and we have leading centers around the world that have a lot of experience with pathologic response, and we're leveraging and identifying these centers to help us coordinate and make sure that this is a rigorous process of pathologic assessment. We're also collecting ctDNA and other biomarkers that will also be very helpful, not in real time in this study, but it's important supplementary information as the -- as we wait for additional primary endpoint time to event.

Great. Thank you, Steven. And certainly, once the sites begin opening and enrolling, that's really where I think the attention natural will be like how quickly are we actually enrolling patients. What do you see from your perspective and your role, what will determine how efficiently Robin moves from all of this builds up to the site activation into actual patient enrollment?

Yes. As Garo and I often discuss, it's not -- I mean, the first patient is very important, and we're on target. But we want to get really accrue quickly, and I think we're setting this up. So it's not the number of sites ultimately, although we're well set up with a global trial, but it's the quality of these sites and their enthusiasm and alignment around identifying and treating the patient. Colon cancer is common, but ROBBIN is enrolling a defined population of stage high-risk 2 and 3 patients that have -- so ideally, we look forward to in parallel, opening a number of early sites and then obviously, as quickly as possible due to regulatory time lines, continue to open sites in early 2027.

Great. Okay. So I have one last question for you, Steven, before the live Q&A at the end. But for all of our listeners and the stakeholders that are following ROBBIN, what are the most meaningful indicators of progress between now and that first patient in that you just alluded to? And then as the study begins enrolling more so, what are you looking for?

So the first thing is the work we've done in the last 2 months, and we'll do in the next 2 months is really rigorously identifying sites that will succeed and produce rapid accrual and high-quality data. So that's number one. And then driving enrollment, and we have a plan for very active connection and really staying very close to these centers as they ramp up. So I think -- but I think in terms of ROBBIN, I think it's best to think of this in 3 stages. You build and activate the network. We're doing that with wholehearted enthusiasm, both from our team and our investigators around the world. You then drive enrollment. And as these responses become apparent, it will only increase the enthusiasm of the sites. And then obviously, getting a readout of the surgical pathology results will be also very, very important. But we are on track to first patient enroll it in the first quarter of next year and getting some pathologic data in the second half of next year as we've outlined previously. But ultimately, it's all about can we -- through bot and bowel and surgery, can we reduce recurrences and improve survival and at the same time, reduce the need for chemotherapy in a curative intense setting. And this will be the paradigm-shifting feature of the study.

Great. Thank you so much, Steven. Thank you for your time and walking us through that today. So Garo, I'm going to come back to something you mentioned earlier at the beginning of the call because this is another area where the team is really focused and also seen some meaningful activity since our last discussion in July. Robin, as you mentioned, is clearly the company's development priority and our focus. But at the same time, as you've mentioned before, our kind of moral obligation that there are patients who need treatment today and physicians who continue to approach yourself and Agenus seeking access to BOT+BAL. Can you give us an update on what has changed across the access program since we last spoke in July?

So just to be clear, we have, as you know, 2 access programs in addition to any trials that are ongoing that allow a patient to have BOT+BAL treatment. One clearly stated is the program that was approved in France. And we have not disclosed the number of patients treated. However, we have disclosed the reimbursement revenue that we get from the French government every quarter, and we will be talking more about the progress that we're making there. So that's a very important program, and French patients have been privileged enough to have access to this and have the government reimbursement. Now in addition to that, we also have the paid name patient program. And that's a program that allows a patient whose physician is seeing it appropriate to refer that patient to a country and a center where the treatment can take place. And these include, of course, as we've talked about before, the U.K., Switzerland, France can treat patients with paid named patient programs that are willing to pay out of pocket in addition to reimbursing their own patients, Belgium, Spain, Brazil, Argentina and the number of countries are growing. Now under this program, a patient can request or the doctor can request to be treated for any indication that they seem to be fit for the patient. It doesn't have to be restricted by the ASC program indications or anything else. As long as there is data, and as you know, we have data on over 9 different kinds of cancers where we have shown consistent activity. In fact, at last year's ESMO in Berlin, there was an oral presentation where we showed the consistency of response rates in late-stage patients that have exhausted all other treatment options. So this is quite exciting actually. It's exciting because we're seeing the momentum develop. And in terms of the named patient programs, for example, we have U.S. physicians referring patients to any country or any center where they can be treated with paid named patient programs. And as long as the physician sees it appropriate to -- for the patient to undergo such a treatment, they can get it. Now the unfortunate reality is that can you imagine a patient struck with cancer, they may not be in the best of health. They may not be in the best of shape to travel. But unfortunately, a U.S. patient has to travel to some other country willing to pay out of pocket and be treated. And we hope that, that reality will change sometime soon. But that's the reality right now. But -- but one of the things that I wanted to also mention is that, as you know, Europe shuts down in the month of August. And in fact, increasingly, U.S. is also shutting down in the month of August. And we expected a slowdown in demand by doctors for August. In fact, we've seen a growth, not a slowdown, but a growth. And so those are very indicative of the fact that there is substantial enthusiasm by physicians and by patients to be treated with blood valve because it can offer them a hope and a reality of survival for an extended period of time. Dr. O 'Day always says the durability of responses with immuno-oncology combinations is really very notable. And so that's what we're seeing, and we're very excited that the roster of physicians who are familiar with the data and are willing to treat patients is growing.

Great. And I know that the team anticipates to share more specifics during our Q3 earnings update. But again, very positive that the interest still continues to grow even over these periods where we were expecting and anticipating maybe some leveling. But you've mentioned in the past, Garo, too, that not just the expansion of additional countries and making the access to BOT+BAL available for their patients, but you're starting to see physicians, repeat physicians treating multiple patients at their centers. What do you think is driving the physicians to come back and seek access for additional patients after they've initiated treatment?

I mean, Stefanie, this is a very important point. Of course, one very important aspect of this, and we've heard this from physicians that most recently have shown very high enthusiasm in participating in our trials. particularly the ROBBIN trial. One very notable reason is that, as I talked about a little while ago, for example, in the last few weeks, we had 2 publications discussing long-term outcomes for patients, one in the late-stage disease and one in the neoadjuvant setting. We expect more to come between now and the end of the year, of course. These are very important drivers, the credibility of the data and their own personal experience. So if you treat one patient and you see something happening, you want to treat another patient. That doesn't mean that every single patient is going to respond, particularly in the late-line setting, that's not going to happen. But it's encouraging because it's last hope for patients. And hope is a very important element here, very important element because how could you tell a patient that we've exhausted all treatments, and there's nothing else we can do for you. So we offer that last hope for the patients who have exhausted all treatments. And that's clear based on the data that's been published and presented. And we also hope for patients in the neoadjuvant setting to be treated less, I should say, less in a punishing way, more in a sustainable benefit. Dr. O'Day explained this beautifully. It's a very important point for patients. And in some cases, what we hope is that patients will be able to benefit from lesser surgery, lesser surgery, meaning some of these surgeries are quite radical debilitating for the patient. For example, if you have rectal cancer or colon cancer that's near rectum, you have a life-changing surgery. I mean we have some patients, including relatives of our colleagues where they have been treated with radical surgery and life is never the same for them. And what we hope to do with the ROBBIN trial is to change that reality for patients. I think this is going to be a very, very, as Dr. O'Day said, potentially life-changing outcome for patients.

Yes. Thank you, Garo. And I know that you had just mentioned, certainly because of the different pathways of these different access programs, both being the French AAC as well as the paid name patient program, which is available across various countries around the world, that offers a lot of accessibility to patients, but that also comes with the responsibility that you've mentioned before. So as physician interest grows, right, and these programs continue to expand, how are you thinking about Agenus' ability to support them in our infrastructure and our personnel? Can you maybe share a little bit about with our audience here what we're doing to ensure safety and our efficiency and then also our response time to support these patients and physicians around the world.

Of course. Let me step back for a moment and recount the fact that the last 2.5 years for the company have been one of the most trying periods in the company's existence. And what's confused us and our colleagues, our scientific, clinical and other colleagues is that we've seen some absolutely remarkable clinical outcomes, both in the late-stage setting and in the neoadjuvant setting across multiple tumors. And I may want to remind you that we had another webcast a little while ago on December 3, where Dr. Christopher Liu of Colorado, he said, there was a patient, he treated. It's in the webcast. And this patient has exhausted all treatment options. And he said our choice was either sending her to hospice or treating her with PPA. And this patient was treated with PPA and the patient is now alive after 2 years, essentially free of disease and conducting a regular life. Of course, this doesn't happen to every patient. But for the patient that this happens, it's a miracle. Nobody can deny that. Now we have been of the mindset, Stefanie, that our responsibility as a company was to take the product to patients on a mass scale as expeditiously as possible. And one of the very important cornerstones of the strategy was to make sure that we have commercial product ready for patients when the product is approved. Now unfortunately, for reasons that everybody pretty much knows, unfortunate for the patients, unfortunate for our company and unfortunate for our investors that, that didn't happen as we expected. However, we have lined up a significant amount of commercial product, commercial grade product ready. And that product, by the way, has a very long shelf life. So if we play right, which we are, of course, this product is good for essentially the next 10 years. And so from a product perspective, we have plenty of product, both but and somewhat lesser valve, but we have the pathway to make more b, commercial valve very, very quickly. And so we're -- we have no product shortage. That's one part of the answer to your question. The second piece is, well, we have product and it may be sitting in a distribution center or 2 hlyated to patients and hospitals or hospitals and patients. And that's where we, a little while ago, announced a collaboration with a company called BAP. And I'm skeptical any outsider but BAP has been an absolute delight to deal with because they have the same focus on benefit for patients as we do. So if a patient under any of our programs, named patient programs in countries where this is allowed to be administered or the French AAC program or any of the ongoing clinical trial programs. We can get product to patients at a lightning speed at a cost that is very modest, very modest and with an infrastructure of professionals, which we're starting to expand, both in Europe and South America, where education is properly provided for physicians such that we can monitor patients' progress with treatment. We can monitor any safety issues carefully and record them. And so these are very important elements of our sense of responsibility in making sure that patients are well served.

Thank you so much for that, Garo. Thank you for that very thorough review and description of the preparations of the organization. So let's switch gears a little bit. So we talked a lot about ROBBIN and how we're moving forward to implementation with Steven. Thank you, Steven, and what we're seeing through the access programs. But to really put the clinical rationale for moving earlier in the disease into context, you yourself, Garo, recently sat down with Dr. Benjamin Schlechter who's treated patients with both BOT+BAL in the advanced colorectal setting. But he as well is also now leading the RECTIFY-1 study, which is a neoadjuvant study in rectal cancer and MSS rectal cancer. So it really gives him a direct investigator perspective on using immunotherapy before surgery. So your discussion range from what neoadjuvant treatment means and why the timing matters to why MSS colorectal cancer has historically not responded to first-generation immunotherapies and really what the long-term BOT-BAL experience has shown. And as you mentioned earlier, why the NEST neoadjuvant findings have really prompted investigators to explore the combination earlier in this disease. So why don't we go ahead and take a look at that discussion from earlier this week?

Hello, Ben. We're joined today with Dr. Ben Schlechter, who is a senior physician at Dana-Farber Cancer Institute. And we've had the privilege of working with Dr. Schlechter for a number of years now, particularly in the context of our lead programs with BOT+BAL. So maybe you can start with defining what the neoadjuvant setting is and what is typically different about those patients in the neoadjuvant setting versus the typical patients in the late-stage setting who are in a much more desperate predicament?

Yes. So in colon cancer and in a lot of solid tumors, we're talking about solid tumors here, not, for example, blood cancers. But in solid tumors, everything rotates around the access of surgery. Surgery is sort of this very important point. And traditionally, we did surgery and then chemotherapy was given after surgery as a helper to prevent recurrence. That's the term adjuvant, adjuvant is a helper. So that was the role of chemotherapy, and we used risk factors at surgery. So the surgery is done. We look at the pathology and the biology, all the specimens of the microscope. We make a guess about how high likelihood it is of recurrence. And then if the likelihood is high enough of recurrence, we give chemotherapy to prevent that recurrence. Neoadjuvant just means the exact same chemotherapy or immunotherapy or other targeted therapies before surgery, and that can be used in a number of ways. Number one is if a tumor is big and scary and just can't come out and you can use neoadjuvant therapy to shrink it. It's actually relatively uncommon. For the most part, that's not the case, at least in colon cancer. But another way to think of it is that surgery is hard on patients in a number of ways. And sometimes, if chemotherapy is challenging and surgery is challenging, chemotherapy is critical, but it could become too challenging after surgery. And so increasingly, in certain diseases it's moved to before surgery as a way of getting it in, letting someone heal and then go to surgery. It's a little bit different when we talk about immune therapy because immune therapy is fundamentally different from chemotherapy. And that's what's really important for the discussion today really is not just what is neoadjuvant therapy, but why is immune therapy so different from chemotherapy and why it's probably better in the neoadjuvant setting, the preoperative setting than the postoperative setting.

So based on what you're saying, patients when they're first diagnosed with cancer, I'm assuming then that their initial reaction is, let's get the cancer out of our body. And so when you are trying to explain why certain treatments prior to surgery, including chemotherapy for that matter, but particularly with immunotherapy makes sense, how do you convince them? What is their reaction typically? And also, what is the interaction between, for example, your discipline as an oncologist? And the surgeon who is typically accustomed to getting the tumor out, provided that, as you said, the tumor is operable?

But they want to do surgery at the moment that is best for the patient. And so if a patient is sick in some way, they want us to get them healthier, but they also want to set the patient up for success. The goal of surgery is to cure patients of cancer. And so if you say to a surgeon, this is a patient with cancer, your job is cure, my job is cure. And I think there may be an advantage to doing a treatment before surgery rather than after surgery, they're going to sign up for that. We're not taking away surgery. We're simply changing the time of surgery so that we can sort of boost the benefit to patients. And so in terms of the surgeons, surgeons can work with this, surgeons know how to work with this. We have many paradigms within colorectal cancer to do this. So within the time that I've been a doctor, we went from -- before I was a doctor of surgery first in rectal cancer and then all these treatments afterwards. And then there was an era of radiation first in rectal cancer and then surgery and then chemotherapy. And now we've moved to all the chemo, all the radiation, everything before surgery, and we finished the surgery. So these are not novel concepts for surgeons and they're not novel concepts for oncologists. The benefit of treatment before surgery with immune therapy in particular, is that surgery does something. Surgery does something good, it removes a big tumor -- but surgery also removes things that are there for a reason. Your lymph nodes play a role in your immune system. Your lymph nodes are the surrounding immune tissue in your colon and every organ really. And there is immune cells in there that are learning how to fight infection and cancer and viruses and all these things. And you have to remove those with surgery because by removing those, you remove lymph nodes that may be contaminated with cancer. But by removing them, you also sort of remove the university system of the immune system. The immune system needs to learn how to fight cancer. And so we have to get those lymph nodes out. But by doing that, we actually handicap the immune system a little. So immune therapy, in particular, after surgery is uneducated immune therapy. And so giving immune therapy before surgery is where you have the most infrastructure to teach the immune system how to fight cancer. So by giving these treatments earlier, and the same surgery you're going to do anyway, you actually end up with a more vigorous immune response because you haven't yet removed those lymph nodes, which play such an important role in fighting cancer even though they have to come out because they could be contaminated by cancer.