Good morning, thank you for joining our mid-year data update event. Before we begin, I need to highlight our forward-looking statement on slide two. I'm Philip Astley-Sparke, CEO of Replimune, and I have with me today Dr. Robert Coffin, our President and Chief R&D Officer. We also have Dr. Mark Middleton, Professor of Experimental Cancer Medicine and Consultant Medical Oncologist at the Oxford Cancer Center and Head of the Department of Oncology at the University of Oxford. Slide three shows the agenda for the call, which will start with a brief further introduction from me, then a brief summary of the high-level updated results by Rob, followed by a discussion of the results of a number of the individual patients by Dr. Middleton. Rob will then provide an overview of what will be one strand of our future development efforts with RP2/3. Following the presentation, we'll be holding a live Q&A. To ask a question, please type your question and click submit in the Q&A section found at the bottom of your webcast. All questions will be held until the Q&A portion of the event. Moving to slide four. We are continuing to make great progress towards our ambition of making our products a cornerstone of immuno-oncology treatment regimens as the most practical and effective way to initiate a systemic anti-tumor immune response. The studies that have been ongoing the longest are with RP1 and our phase II skin cancer cohorts, which support the two studies we're running in cutaneous squamous cell carcinoma and anti-PD-1 failed melanoma with registrational intent. We have always said from the get-go, our modality and products can result in a high rate of complete response. It is these responses that transform lives, give patients the potential for cure, and relieve them of disabilities and/or disfigurements caused by disease. Seven out of nine of our cutaneous squamous cell carcinoma responses are now complete ones, with a further patient to be assessed as a probable eighth complete response pending biopsy. Further, in melanoma, a number of our partial responses have been shown to be metabolic complete responses by PET scan. While this further supports our expectation for a positive outcome in our registration-directed studies, we also believe if our well-tolerated products are pushed earlier into disease courses, the rates for complete response could go higher still and result in many patients never developing the type of end-stage disease we are currently treating. With RP2, the signal in patients with failed anti-PD-1 has really picked up from where RP1 left off and reconfirms the ability of our platform to treat anti-PD-1 failed disease. We look forward to presenting the updated data in this regard today. We also look forward to explaining our decision to advance RP2 or RP3 into later-stage development to treat patients with liver metastases with very poor prognosis, where we've seen very encouraging reproducible activity. We've also made solid progress putting in place the building blocks to build an entity capable of transforming the immuno-oncology landscape. Our own manufacturing facility is fully operational, filling GMP batches, and we've agreed a path forward recharacterization release assays with the FDA. In addition, we've hired a chief commercial officer who is starting the planning process to ensure, if approved, our products are widely adopted in the marketplace. Finally, we have a strong balance sheet to execute on our vision. As a reminder of our technology and MOA on slide five, oncolytic immunotherapy is the use of viruses that when injected into tumors, partially or completely destroys them through virus replication, bursting the tumor cells open, and exposing all the released cancer antigens to the immune system in an environment of necrotic cell death. This leads to activation of a patient-specific systemic immune response and the destruction of uninjected deposits. We believe that herpes simplex virus is an optimal species of virus for oncolytic use, it being both highly lytic and inflammatory and having the ability to carry multiple immune-stimulating proteins into the tumor microenvironment to further amplify the immune response. Our next-generation constructs have been specifically designed to maximize each of immunological signals I, II, and III in harmony to provide full activation of adaptive immunity, combined with the potent activation of the innate immune system as well. Our strain of HSV has been deliberately selected for its lytic properties in human tumor cells, and from all our products as our base platform, we express a fusogenic protein that greatly increases direct tumor killing, immunogenic cell death, and systemic immune activation. These design features ensure maximum presentation of antigen on the MHC and antigen-presenting cells, or so-called Signal I. We then express various proteins from the virus intended to maximize co-stimulatory signals at the antigen-presenting cell and T cell interface, or so-called Signal II, to ensure optimal T cell priming. Our lead product, RP1, additionally expresses GM-CSF. RP2 additionally expresses an anti-CTLA-4 antibody to stop the negative feedback loop at the CD28 CTLA-4 axis. RP3, two further immune costimulatory pathway activating proteins targeting CD40 and 4-1BB, which also lead to downstream inflammatory cytokine release, or so-called Signal III. Moving to slide six. We believe our products are the most practical and effective way to ensure a tumor is recognized as foreign, where there's an absence of an effective pre-existing immune response. Practical, as all our products are off the shelf. They come in a simple vial. Manufacturing is relatively straightforward and cheap, and our products are well-tolerated. Effective. While the approach is off the shelf, it is also patient-specific and acts as a pan-universal neoadjuvant vaccine as the tumor is sliced open and all the cancer antigens within are exposed to the immune system in an environment of necrotic cell death, a major immune danger signal. Our approach has multiple further MOAs packed into one product through the expression of immune-stimulating proteins, which are carried into the tumor microenvironment to further amplify the immune response, as I described on the previous slide. Our development plan is shown on slide seven. The data we're providing an update on today pertains to the top two bars, where we fully enrolled the 30-patient melanoma cohort containing both PD-1 failed and PD-1 naive patients. We are close to fully enrolled in the non-melanoma skin cancer cohort as it pertains to the first 30 patients who are anti-PD-1 naive, of which 15 patients have cutaneous squamous cell carcinoma. However, this cohort has now been expanded to include non-melanoma skin cancer patients who have failed anti-PD-1, where enrollment is now underway. As a reminder, we have two registrational studies ongoing in cutaneous squamous cell carcinoma and anti-PD-1 failed melanoma, as depicted. We are also providing an update on RP2 as a single agent and releasing initial data for the first time with RP2 in combination with Opdivo. However, it should be borne in mind that this data set is immature in as much as they include many patients who remain on therapy and may therefore further respond or progress. Finally, we intend to expand development of RP2 through beyond phase I and will be giving our initial thoughts on where we plan to focus our efforts during 2022 during the course of this presentation. I will now hand on to Rob to summarize today's data sets. Thanks, Philip. I'll just now briefly summarize the data update today, which is for RP1 in skin cancers, as Philip said, and for RP2, before I hand over to Professor Middleton, who'll present the data in much more detail. First, for cutaneous squamous cell carcinoma, as Philip said, we've now enrolled 15 patients into the IGNYTE study, with CSCC. This shows that while we recently enrolled a number of patients with a particularly high tumor burden who quickly went off study, which Mark will discuss a little bit as well, the theme of achieving a high rate of response and particularly complete responses continues. The complete response rate in this group is now 46.6%, with two additional complete responses since October and one further response awaiting biopsy confirmation, which would bring that to 54.4% if that biopsy shows to be negative. The response rate in CSCC is now 60% with continued very good durability of those responses and multiple responses now out over 600 days. In our fully enrolled melanoma cohort of 30 patients, the registrational-directed indication we're also pursuing, the objective response rate in anti-PD-1 naive patients is now 62.5%. For anti-PD-1 failed patients, it remains at 31.25%. Remember, that cohort fully enrolled early last year, and so is now really quite mature. With again, very good durability being seen and multiple patients now having converted from originally stable disease or partial response to now complete response. We now have 11 patients with other non-melanoma skin cancers enrolled, and clinical activity continues to be demonstrated across the breadth of these different cancers. We've also found, interestingly, that giving a second course of RP1, the initial first course is only eight doses over a couple of months. A small number of patients may benefit from additional doses of RP1, those being patients who achieved an incomplete response or progressed after initial response. Where in a very small handful of patients we've now done that, this has been seen to be well-tolerated, and also each of the patients has shown evidence of clinical activity, which is something which we think is quite unique in oncology drug development. The data with RP1 in skin cancers continues to show that the combination with Opdivo is well-tolerated and that the combination drives deep and durable responses, which we do believe strongly supports our registrational-directed activities in both cutaneous squamous cell carcinoma and in anti-PD-1 failed melanoma. If we now move to RP2, a brief summary there. With regard to the single agent part of that study, that was fully enrolled last year, and we presented initial data in October, and there were three out of the nine patients enrolled who had responded. These patients with further follow-up have continued to show good durability, with the patient with mucoepidermoid carcinoma, who was a complete response in October, maintaining that out now to 15 months. The patient with esophageal cancer has maintained very good partial response now out at 18 months. The uveal melanoma patient progressed at 15 months, although obviously showing quite impressive durability before that. Relevant to our liver metastasis strategy, which Philip mentioned and which will be discussed later, three of those monotherapy patients had injections into the liver of RP1, and all three of those patients showed evidence of activity following those injections. If we move on to RP2 in combination with Opdivo, the new data which will be presented today, there are 27 patients who've been enrolled into that combination portion of the study so far with a range of different tumor types typical for a phase I trial. We now actually currently intend to expand the number of patients in that study with liver metastases to be treated with RP2 also to provide further support to the liver met strategy, which we'll come to later. While this data is still rather early and immature, so far out of the 27 patients, many of which still ongoing treatment, six have achieved an ongoing response in patients with uveal melanoma, cutaneous melanoma, and head and neck cancer, all of those patients having had prior anti-PD-1, and which at this early and immature stage of the study, we think is very promising and also has reinforced the signal we'd previously seen in some of those tumor types with RP1 in the past, and which is supporting our registrational development at the moment. With that very brief summary, I'll now hand over to Professor Middleton, who'll go through the data in somewhat more detail. Professor Middleton, as Philip said, is our lead investigator in Oxford, who's been extremely important in our enrollment to date and really has recruited the most patients of any investigator at any site globally, has by far the greatest experience with both RP1 and RP2 of anybody. He really is the perfect person to describe the data in detail. Over to Mark. Thanks, Rob. To start with RP1 in the IGNYTE study, where it's given in combination with nivolumab, just to review that for melanoma, we're now concentrating on patients who've failed PD-1-directed therapy and also enrolling a non-melanoma skin cancer cohort. The nivolumab is given in the standard way for up to two years, the RP1 is given every fortnight as an intratumoral injection for eight doses initially, that completes treatment well within three months of starting. Although we can inject the RP1 directly into superficial or palpable nodal tumors, we also use image-guided injection quite a lot, we can access deep tumors, including in visceral organs such as the liver. Since the start of this year, we've had the option to give up to eight further doses of RP1 according to clear criteria specified in the protocol, so for single progressing lesions or where we think a response is stalled and would benefit from further treatment. We've got some very early data of this, which is a pretty unusual approach in oncology because generally the principle has been that once you've tried it, if it's not working, then you leave that off and try something different. Moving on to talk about safety. Broadly speaking, the safety information is unchanged from the previous presentation, with treatment pretty well tolerated and with the toxicities that you might expect for patients who are receiving nivolumab. There has been one significant toxicity in March of this year. A patient who had already completed their RP1 course, who was on the nivolumab maintenance phase of treatment, developed a myocarditis, which we think associated with the severe and succumbed to that. The investigator assessment of this is clearly related to the nivolumab rather than to the RP1. Otherwise, as the table shows, it's a very well-tolerated regimen. Moving on now to talk about efficacy in this situation and focus initially on non-melanoma skin cancer. This table summarizes the response data, and you'll see in the red columns, focuses on the changes that there have been since October. As Rob touched upon briefly, we've enrolled four more patients with cutaneous squamous cell carcinoma. I think it's probably fair to say that I and my fellow investigators gave RP1 a pretty hard challenge enrolling some very advanced patients who've not benefited from treatment. In fact, all of them progressed very, very quickly and a batch of patients that in retrospect didn't precisely meet the bill with their rapidly progressive disease. Having said that, as Rob's already touched upon, we've seen some of the responses that we previously reported deepen, so that now seven of the responding patients have got complete responses, and there's the potential for one more to join them in the near future. We've also seen additional responses in other tumor types, basal cell carcinoma, Merkel cell carcinoma, and angiosarcomas, all of which are listed in the subsequent columns. A broad spectrum of activity across an important set of patients. Just to go into a little bit more detail, apologizing for the slightly gruesome slide, it does speak to the issue of the severity of the disease of patients that we've enrolled since the last briefing, both pictorially here and also looking at the scans of very, very extensive tumors that defied treatment, led to rapid progression, and then leaving the study within a couple of months to move on to palliative care. If you look at the waterfall plots describing the extent of response, what you can see here, color-coded according to histology, it is how deep these responses are, with a very significant proportion of patients experiencing complete response, both radiologically and with the potential for more to join with a number of patients still on treatment. Looking at that in spider plot terms, sorry, swimmer plot terms to show the duration of that. Again, Rob gave the headlines earlier. We're now starting to see patients approach the two-year mark in complete response, and some with deep partial responses. The durability of response has been very impressive across this cohort, and indeed with other patients who've been treated with RP1 and RP2. To look at this another way, individual by individual on the spider plot, what you can see here is the depth of that response, the speed over which it develops, which is often quite quick in this patient population. There's merit in persevering with treatment because there are some examples of patients who have a modest response initially, which then deepens significantly over time. I draw your attention also to the right-hand part of this plot where you see a patient who has reinitiated. There's a small uptick in the line, then you see it going down again as a result of reinitiation of therapy. We'll talk a little bit more about that in a few more slides' time. Updates on individual patients now, for patients since what we talked about back in October. If we look at this patient here who's a new complete response, it's subtle, but what you can see in the baseline scan in June is deformity of the maxilla. You can see how it's pushed back where the tumor is, with ongoing treatment at six months at the end of last year and now early this year where we've got a complete response, what you can see is normalization of the architecture in the round back. That obviously has very, very profound consequences for the patient in terms of how they feel, how they look, as well as being impressive on the radiology. A second patient who we reported previously as a partial responder on the basis of the pictures we've seen in May and in October of last year has had further treatment, which has now converted this to a complete response. What's really important is that, as you might expect, looking at these pictures of the patient's foot, she's regained full mobility, having previously been unable to walk on that foot. It's not just pictures on a scan, but a very important and practical difference to the patient's life as well. We've got in this slide set now describes a partial response for patient with basal cell carcinoma, and we think that this may in fact be a complete response because as you follow the scans from October through to February, you can see that they are approximating normality, and it's half unclear whether this tumor, which incidentally is a patient who failed vismodegib, the standard of care in this situation. We're increasingly optimistic that this represents scar tissue, and so the patient will have a biopsy to see whether this is the case and may end up being a complete responder. Finally, to look at a patient with Merkel cell cancer, what we see here is a very impressive response in the injected lesion in the top panels with a very significant mass, five centimeters in diameter, also an observable response in an uninjected lesion, which again is tending towards normality. We'll need to get biopsy to prove whether this is a complete response. I'm now going to turn to the data for melanoma in with the combination of RP1 and nivolumab. What you see here is a summary of the disposition of the patients treated so far in the initial cohort were principally patients with cutaneous disease, although we do have some with mucosal and uveal melanoma. I think it's important to note that this is a relatively advanced population, with the majority of patients having prior exposure to PD-1 agents and being of a relatively high M stage, with over three-quarters of the patients having M1b or C disease. This is by no means a highly selected population. Again, same format as with the non-melanoma skin cancer. In the red column, we've got the update compared with what was presented in October of last year. This is a relatively mature cohort because enrollment completed early last year. What you can see here again is a similar story with increasing responses across the piece, and we're seeing deep responses within the anti-PD-1 naive cohort, now three complete responders, an overall response rate of roughly 2 in 3, and then a response rate of about 1 in 3 in the PD-1 failed cohort with a complete responder, as well as four partial responders, one of whom we have assessed as a metabolic CR. Looking across at the mucosal data, we've got a complete mucosal responder. That was a patient who we previously reported as having a partial response, and stable diseases, but still with the potential to respond, albeit at a late stage in the uveal cohort. We'll talk a little bit more about uveal when we discuss RP2. Looking at the waterfall plots, again, what you can see is a high proportion of patients with complete responses, which I think is significant and marks out this approach for treatment from some of the other IO drugs in development. The swimmer plots, again, a similar story to what we've presented already in the non-melanoma skin cancer, with lots of patients still on treatment, starting to approach that two-year mark, and with enduring responses, whether partial or complete. With the spider plot, perhaps a slightly slower trajectory towards the best response than you see with the non-melanoma skin cancer. Again, I draw your attention to a patient with stable disease who then progressed and then responded to reinitiation of PD-1, which in fact is one of my patients who had failed anti-PD-1 before joining the study, had a prolonged period of stable disease, and then re-responded and was closely achieving a PR based upon reinitiation of treatment. Just to talk a little bit more about reinitiation. As I said before, this is a relatively unusual approach, but it speaks to the ability, based upon the mechanism of action, to get a subtly different response from injecting a new lesion or a lesion that's progressing in the face of prior successful or reasonably successful treatment. It's an opportunity to deepen responses that we've already achieved or to achieve a response once more where it's been lost, often locally in an isolated lesion return. We've got evidence of activity in all four of the patients that we've treated so far, we're still at a very early stage. There's an example here of a patient not treated at my center, but in Liverpool by Dr. Joe Sacco. What you can see here is the baseline scan on the left, the initial response to therapy through until March of last year, local regrowth of the tumor at the beginning of the year, and it was at this time that we again, through a protocol amendment, were able to reinitiate treatment, and that was done with a resulting complete response evidenced on the far-right picture at the middle of last month. To talk a bit in a bit more detail about RP2 now. Next slide, please, Rob. The key eligibility criteria here, again, a broad set of tumors eligible, RP2 given again every couple of weeks for eight doses with nivolumab started with the second-highest dose and being able to be continued for up to two years. Again, in exactly the same way as has been with RP1, we didn't specify that we had to go for superficial known tumors, and we've, particularly in Oxford, been enthusiastic users of image-guided injection to broaden the scope of patients that we can treat. Slightly earlier than the RP1, we had the opportunity to reinitiate treatment with RP2 in the fall of last year. This table summarizes the patient disposition. As Rob highlighted at the beginning, we have nine patients in the RP2-only dose, which previously have been reported, and we've got 27 of the 30 patients enrolled in the combination. It's a broad spectrum of tumors, but you'll see that we have melanoma very well represented, including uveal melanoma, some squamous cell cancer of the head and neck, and a range of sarcoma as well. Safety has been very tolerable. The majority of patients experience only Grade 1 and 2 toxicities. This is very similar to the story that we've seen with RP1 in a larger patient set. Insofar as we have some higher-grade side effects, they're all very consistent with either injection and often not with disease, but procedure, not with disease or the IMP, but procedures to deliver it all with nivolumab or with the RP2. Just to summarize briefly, the monotherapy sure spots, we've talked about these responding patients, the uveal melanoma patients who were treated in Oxford. Sadly, we lost control of that excellent response after 15 months, and the patient progressed and died very rapidly. I suspect that COVID was a factor in being able to seek medical attentionObviously came from some way away and had that dealt with promptly. I'd also draw your attention to the top patient, whom again Rob had mentioned previously, another patient with mid-esophageal cancer and liver metastatic disease who's had an excellent partial response. Incidentally, this patient had been treated in a clinical trial and therefore had been exposed to an anti-PD-L1 agent as well as to chemotherapy before joining the study. We were able to confirm with a PET scan last month that there was no metabolically active disease remaining, although we can't claim a complete response because there are still visible lesions on cross-sectional imaging. I think this points to the exciting potential for RP2 to produce deep and durable responses. We move on now to the patients who received RP2 in combination with nivolumab. We've got, across the whole cohort, a response rate of just over 20%. There are still a significant number of patients in whom it's too early really to determine their ultimate disposition as far as treatment is concerned, because these data really aren't very mature. I would draw your attention, though, to the patient with cutaneous and uveal melanoma, where we've got ongoing responses in patients who've had significant prior exposure to immunotherapy. Looking at the swimmer plot, you'll be familiar with this story now. Obviously, we're a little bit earlier in the piece, therefore we don't quite go out to the 700 days that we were able to look at with RP1. What you can see here is a number of patients ongoing with treatment now getting on to the six-month mark with good responses. Interestingly, as for RP1, a number of patients who showed initial progression, including new lesions, have had responses thereafter. Raises the question of whether these are inflammatory reactions to the therapy inconsistent with the mechanism of action. I think one of the learnings that we've taken from the whole program is that once started, it pays to persist with viral injection and the nivolumab out until at least the completion of the viral injection part of the treatment before taking a view as to whether there's patient benefit. Just to talk through this with some examples. This is a patient of Professor Harrington's at The Royal Marsden Hospital with uveal melanoma. What you can see here is a local tumor recurrence. The patient also had bone metastases, which are not shown here. This patient had a new lesion. This is a tumor in the socket, which you can see in the picture as well, dated October of last year. As the scans and the picture show, there's very good resolution of the tumor. Again, this has a significant impact upon quality of life as well as longevity. There's a further example from Dr. Sacco. Again, this is a patient with cutaneous melanoma who'd had prior exposure to nivolumab, had bulky disease in the neck as well as small lung lesions, and there'd been substantial initial progression. If you look here at the baseline scan and focus on this lesion in the upper neck circled in red, you can see that over the course of the first three months, there was considerable progressive disease. We've learned to grit our teeth to carry on with treatment, and you can see here that another 3 months down the line, this has achieved a partial response as the impact of treatment starts to take hold. This was associated with stability in the more disseminated smaller lesions and significant functional improvement that's allowed the patient to return to work after a considerable amount of time unable to do so. Finally, a patient with squamous cell cancer of the head and neck who'd had prior exposure to anti-PD-1 in the form of nivolumab, as well as standard fluoropyrimidine and platinum chemotherapy, as well as radiotherapy. What you can see here is an injected and uninjected lesion, both of whom are responding to treatment in perhaps a more conventional way within a couple of months of initiation of the treatment. In summary, RP1 combined with nivolumab continues to provide deep and durable responses in a range of skin cancers and remains pretty well-tolerated. What's new compared with previous presentations is that we've got some experience now of reinitiation with RP1, which remains very well-tolerated and for which we've got early indications of clinical activity in all four of the patients treated so far. We recall that biomarker data presented at AACR continues to support the mechanism of action of the agent and broadly speaking, turning cold tumors hot. As far as RP2 is concerned, it's very well-tolerated, whether given alone or in combination with nivolumab, and we continue to see exciting initial activity in patients who failed anti-PD-1, and also in a range of patients with cancers that perhaps haven't hitherto been considered to be particularly amenable to immunotherapy. I'm going to hand back to Rob now, who's going to talk about some of the development plans that Replimune have. Great. Thank you very much indeed, Mark. That was wonderful. We're now going to move to a bit of a discussion as to how we're intending to move beyond skin cancers, particularly with RP2 and RP3, and in particular, our plan is to initiate a relatively broad development program in patients with liver metastases specifically. As everyone will be aware, the liver is one of the most common sites of metastatic disease, including for many of the larger tumor types like lung cancer, breast cancer, colorectal cancer, et cetera. The prognosis for these patients is particularly poor, and they also respond particularly badly to immune checkpoint blockade. This may be due to the fact that liver metastases appear to selectively remove tumor-reactive T cells from the circulation, which I'll come back to in a minute. As oncolytic immunotherapy aims to directly kill tumors and also unleash a systemic onslaught of tumor-reactive T cells, the hope is that with RP2 and RP3 particularly, we'll be able to reverse that, which our initial data suggests may indeed be the case, some of which Mark alluded to and showed. This slide shows the numbers of patients with liver metastases in some of the larger indications, showing on the left that the potential commercial opportunity in just these three highlighted indications is around 80,000 patients per year in the U.S. alone. On the right, the proportion of patients with liver metastases from a broader range of tumor types is shown, which altogether, as you can see, adds up to a very large number indeed, such that the potential market is clearly very substantial indeed, if one had a therapy which was able to provide activity in patients with liver metastases. Sorry, I'm experiencing a bit of a delay. On slide 48, this shows on the left that patients with liver metastases treated with immunotherapy tend to fail at distant sites rather than only in the liver. If they only had liver mets in the first place, they don't actually tend to fail locally, they tend to fail systemically, which really does indicate a systemic deficiency in immune activation, and that on the right, patients with liver metastases across tumor types also achieve less benefit following immunotherapy than patients who don't have liver metastases. Whereas interestingly, this difference isn't seen with things like chemotherapy or targeted agents. The difference between liver and non-liver mets is actually specific to immunotherapy, the immunotherapy which is particularly impacted negatively by the presence of liver metastases. If one then looks specifically at the response rate and survival across tumor types to immunotherapy, these are both reduced in patients with liver mets, as you can see, where survival is considerably impaired in patients with liver mets, as is the response rates achieved across these tumor types mentioned in the slide. A recent publication on slide 50 looked into the mechanism by which liver mets patients do particularly poorly on immunotherapy. This is still somewhat hypothetical at the moment, the data does seem to back it up. This indicated that macrophages which accumulate in liver metastases present antigens derived from tumor, which can then bind antigen-reactive T cells, which are then killed by apoptosis induced by the macrophage via the FAS pathway. Therefore, T cells which react to the tumor are selectively depleted in the systemic circulation, resulting in poor systemic efficacy of immunotherapy. If, however, we're able to kill off the tumors in the liver, for example, with RP2 or RP3, that would reduce not only the tumor in the liver, but also the number of macrophages associated with that tumor, which should effectively remove the T cell sink, if you want to think about it in that way. While at the same time as inducing an army of new tumor-reactive T cells to increase overall systemic efficacy. With RP3 in particular, the expression of CD40 ligand and 4-1BB ligand should also reduce the degree of T cell apoptosis and also increase T cell activation, further enhancing the therapeutic effect. All of which suggests to us that there really is a particular opportunity for us in patients with liver mets, which we're hoping to exploit. This next slide, which there may be a little lag. This next slide does show a number of patients so far we've treated with liver mets, which really we do think is pretty impressive, bearing in mind the nature of the disease these patients had. There are six patients here, all of which had substantial tumors in the liver, some of which were injected in the liver, and a couple of which were injected at other sites, and some of which were treated with RP1 plus nivolumab, and others with RP2. What in aggregate it shows are that patients with liver metastases can not only respond, but respond systemically and also have very good durability of effect as well, with one of these patients out now to nearly two years following initiating therapy. This body of data we really do think supports that we really can potentially do useful things in patients with liver metastases, which inspired us to begin this development pathway for those patients. Our development strategy in patients with liver metastases described in outline here is still early and work in progress. The plan at the moment is to initially expand enrollment into the RP2 study to include patients with specific tumor types with liver mets, including from GI cancers, lung cancer, and breast cancer, together with a few additional patients in uveal melanoma to further confirm the signal we're already seeing in uveal melanoma with RP2. In parallel, we'll be continuing to assess the safety and clinical activity of RP3, which includes patients with liver metastases. We're currently in the Phase I dose escalation single-agent part of that trial, and we'll move to combination therapy later in the year. Depending on the data we see with each of those, RP2 and RP3, we'll then initiate a multi-cohort Phase II program in liver met patients with specific tumor types, which will provide us with further signal confirmation and tell us which tumor types we have the strongest signal in and where, therefore, to enter registrational development. It's a stepwise approach, which should be able to be relatively rapidly executed and will be very much data-dependent. The exact details will depend on that data as it will, whether it's RP1 or RP2, sorry, RP2 or RP3, which is used in a particular circumstance. All of that will kick off later in the year with the expansion of RP2 into further patients with liver mets. Slide 54 sums up the prior comments I've just been making and reiterates that based on the theoretical considerations, the huge unmet need in patients with liver mets and on our emerging data, that we believe liver mets to be a very real opportunity for us, which is worthy of aggressive development as we so far mainly apply to patients with skin cancers. We're now aiming to take a similarly aggressive approach and proceed hopefully rapidly through development in patients with liver mets as well, particularly with RP2 and RP3, which were specifically designed to try and treat patients with less immune responsive tumor types than we're currently targeting with RP1. With that summary of our expanding strategy, I'll hand back to Philip, who's going to do some summing up. Sure. Thanks, Mark. Looking ahead over the next 6-12 months, we look forward to being able to share further data across our programs to support our ability to treat patients who have failed anti-PD-1 across a broader swathe of tumor types, including initial data in anti-PD-1 failed cutaneous squamous cell carcinoma and anti-PD-1 failed non-small cell lung cancer. We also look forward to presenting around the year-end single-agent data with RP3 and providing more details on the Phase II program we plan to run with RP2/3 in patients with liver metastases from prevalent tumor types. The responses with high lytic strain in liver are profound. They include single-agent responses, they include PD-1 failed responses. They're deep, durable, and provide a very large value opportunity beyond our skin cancer franchise. In skin cancer, we're maintaining guidance. We expect to release top-line data from our two ongoing studies with registration intent in CSCC and anti-PD-1 failed melanoma in 2022, and we'll provide further details on timing expectations later in the year. We'll now turn over to Q&A. As a reminder, if you wish to ask a question, please type your question within the Q&A bar located at the bottom of the webcast and click submit. We'll get to as many questions as we can. Thanks again for everyone's time this morning, and we now look forward to answering your questions. Philip, we have a question. Patients recently enrolled with high tumor burden CSCC. Would these patients have been eligible for CERPASS based on inclusion, exclusion criteria? We would have to look at the patients in detail to determine that. It's quite likely based on other inclusion criteria not relating to tumor burden, relating to comorbidities and performance status that they wouldn't have been eligible. I can't formally answer the question. We do have to remember in CERPASS it's a randomized controlled trial, therefore there would be expected to be a balance of such advanced patients between the arms if they were to be enrolled, which would mean that the trial would not be negatively impacted one way or another by enrolling such patients. Thank you. We've got a question for Dr. Middleton. Dr. Middleton, how confident are you that you are seeing abscopal effects that is not oncolytic virus spreading by, for example, leaky vasculature? I think very confident indeed. The majority of patients who retreat have had prior exposure to herpes simplex virus or carry antibodies that would neutralize any virus that escapes into systemic circulation. If we look across the range of data that we presented previously and today, what you can see is clearly distant tumors which are responding. It's not possible to put that down to viral leakage and a direct effect. This is an immune-mediated effect by tutoring the immune system to act systemically on the basis of local cell death. The fact that we can then see that again, that reinitiation further supports that potential. Great. We've got another one for you, Dr. Middleton. What are the disadvantages of using oncolytic virus versus antibody or small molecule-based therapies? Do oncolytic virus limit the potential uptake in academic centers? The obvious disadvantage is that current systems of care are very well set up for intravenous or oral drug administration, and you have to learn a new way of doing things in order to administer things intratumorally, and you have to have the cooperation of skilled interventional radiologists to access visceral tumors. One of the reasons we've been able to contribute so significantly to this program is because we have those capabilities in place in Oxford, and they're by no means special to Oxford. Interventional radiology is available in almost all major hospitals in the Western hemispheres. It's used for well beyond cancer as well. Where we have effective treatment, then experience tells us that uptake will be enthusiastic. I can tell you that our radiologists were extremely enthusiastic, having had to be persuaded that this was a program we wanted to pursue. They can see the fruits of their labor from scan to scan, from cycle to cycle, and they're very vested in the program. Although it undoubtedly adds a layer of complexity and you have to be prepared to manage the small number of side effects that go with deep injections into viscera, it's by no means insurmountable. If you compare it with the complexities associated with intravenous adoptive cell therapies or bone marrow transplantation, they're trivial. This is something that can be sorted out if you've got the efficacy signal. Great. We have a question on dosing, Philip. Are you planning to extend RP1 to dosing beyond eight doses for all patients? Do you think this could extend the durability or response? No, we're not. We do think that the eight doses, we got it about right. The vast majority of patients have up to eight doses. In some cases, there's, in quite a few cases, nothing left to inject well before that full eight doses, and then achieve good durable responses, which in nearly all cases has remained ongoing to date. It's only been a very small handful of patients who it has been thought could benefit from a further course of up to eight doses. We are now comfortable that having the initial dosing regimen of a first course of up to eight, and then the allowance for the small number of patients who may benefit from a second course of a further course of up to eight really is right, and we have no plans to amend that further. If I could just add from a physician's perspective, the ability to retreat or reinitiate RP1 makes a massive difference. With all immunotherapies, whether it's nivo, ipilimumab, when we first started using that and so forth, there's always been a question how long we go on for, and we all strongly suspect that we over-treat patients. We were very pleased with the initial eight injections only approach because it draws a line, and we saw patients who continued to respond and have deeper responses after the end of injection, which gave us a lot of confidence that we had triggered an enduring change in the immune system. The fact that you can say to a patient, "Look, we go with eight, we know we can get good results with that, but if it happens not to be right for you, we know we can come back and give more," is, I think, a hugely better approach than "We're going to sign you up to have an injection in your liver every two weeks for all time. I think if we go back to this slide, it is worth pointing out here in relation to these patients who got single agent RP2, the treatment course for single agent RP2 in the phase I part was actually just five doses to really just sort of get the phase I part done more quickly. Highlighted in the green. As you can see, the patients didn't actually fully respond, the responding patients, until after the period of treatment, and then those responses continued to deepen. None of these patients have had any other therapy with anything else since these first five doses of RP2. We really are achieving deep, durable effects following a short initial course, and just having the opportunity to give a second course in the relatively rare cases where that might be needed, we really do think is quite novel and also about right as Mark was highlighting. Okay. Moving on to liver mets. When treating liver metastases, would the clinical approach be to inject only tumors in the liver or also inject the primary tumor organ? I'll answer the question, and Mark can further comment. The rules for dosing of patients are really you dose the largest easily injectable tumors, and you have up to 10 mils of injectate to use on each injection day. If the largest easily injectable tumor is in the liver, you'd inject the appropriate volume into that tumor, and then if there's any leftover of the 10 mils, you would inject into other injectable tumors, which may or may not be in the liver. In many cases, and in most cases so far, where patients have been given injections into the liver, they just get the full dose into liver. There may be some occasions where they get injections into both liver and elsewhere. We've been slightly changing our approach in Oxford based upon the results that we've seen today. I consented a patient to this program yesterday who has a relatively small subcutaneous lesion on their back and has liver disease. Perhaps two or three years ago, we'd have said, "Well, we'll go for the low-hanging fruit. We'll inject a small amount of virus into the surface lesion and see what that does." Based upon what we've been seeing to date, we're keen actually to inject the full 10 mils. We'll be injecting a right-sided liver lesion in this patient as well as the subcutaneous disease. That's not driven so much by the Nature Medicine paper that Rob referenced, but by the observation, and the two patients that Rob called out in the RP2 only slide are good examples of that. We've seen some really impressive results in patients with predominantly liver disease by injecting one lesion there, and in a way that is out of line with what we've come to expect with IO, where it's often the site that does less well. We're interested, obviously, or when we've discussed with the patient what's involved in participation, we're frank about the slightly increased risk by introducing a needle into a vascular organ like the liver. I'm happy to say that I think that the risk-benefit falls on the side of benefit for this because of what we've seen, acknowledging that the data aren't there and so forth. We can also look at these examples just to further illustrate that if we go through these patients. This patient just had injections into the liver. This patient likewise just had injection into the largest liver tumor. They did have disease outside of the liver, a much smaller disease. This patient only had disease in the liver, but quite a number of tumors in the liver, as you can see, and just the largest one was injected. Likewise, this patient, I believe, is one of Mark's, only had disease in the liver and was injected in the liver. This was an MSI high patient. Again, disease in the liver, injected the largest tumor in the liver. This patient was interesting. This patient had quite extensive disease in the liver, but actually it wasn't the liver which was injected. The tumor which was injected was in the thigh, but both the thigh and the liver responded to achieve a complete response, which is ongoing. This final patient had quite a lot of disease in the liver where just one lesion, the largest, was injected in the liver. The patient also had quite a lot of disease outside of the liver, none of which was injected and all of which responded, and this patient is ongoing partial response now. In actual fact, a PET scan was done a day or two ago, and none of the sites of disease are avid any longer, including large tumors in the lung. Dr. Middleton, this question is for you. Does the LAG-3 plus PD-1 data from Bristol change the way or the way to use potential oncolytic virus therapy? No. I would add that we at Replimune are very keen to combine with things which aren't anti-PD-1, including additional promising immune modalities. That includes things like anti-LAG-3, anti-TIGIT, also molecules which impact the macrophages in the tumor microenvironment as well or regulatory T cells. We're also interested in combining with things which aren't immunotherapy at all, combining with standard chemotherapy agents and targeted therapies where we think there could be a lot of potential value there, particularly to combine with standard of care in tumor types which are not currently treated with immunotherapy. Yeah. To expand on my answer, I think where we start to see the potential for changes in standard of care in early lines of treatment, that might certainly change the patient population, for example, in melanoma that comes to us as a PD-1 progressor. I think the bottom line is that if we look at the therapeutic landscape at the moment, I don't foresee any significant changes which mean that we end up with a fundamentally different patient population that might have a different response to this approach. If we look beyond melanoma, I'm a big fan of combining immunotherapy with chemotherapy. I think that the data from non-small cell lung cancer, the early data from esophageal cancer, which is my other tumor area of interest away from drug development, point to the potential there. This program is in its early stages. It's asking a very particular question. I think it's asking the right questions to its next stage of development. With infinite time and resources, then one could see adding it in much earlier in the patient pathway, and in combination with chemoimmunotherapy, for example, as being a reasonable way to go. As you'll know, these are significantly more expensive and therefore potentially riskier studies, and I leave it to the company to discern when they have the runway and the data to support that breadth. Yeah, we haven't gone into that level of detail yet, but the RP3-2 liver mets program isn't intended to be limited to only combining with anti-PD-1, but also potentially combined with actual standard of care in tumor types where anti-PD-1 isn't active or approved. Next question. It seems that persistence pays, where continued treatment often results in PRs after PD-1 therapy. How is this built into the study protocols, and what is the plan to treat patients through pseudoprogression in future clinical trials? I'll comment first, and Mark can further comment. Our protocols already allow for pseudoprogression to the extent that progression needs to be confirmed on two scans for the patient to go off therapy. If they see progression on a first scan and it's felt to be clinically warranted to continue, the patient gets then consented to continue therapy past progression and carry on treatment. As you'll have seen, a number of patients where that has occurred, patients have then achieved response. Our response criteria require that for progression to count as progression, it has to be confirmed. If it isn't confirmed, then they achieve a response, then their best response is still that response. The protocol also allows for treatment for up to two years with the anti-PD-1. They get the short course of RP1 or RP2 or RP3, then they carry on with the anti-PD-1 for up to a standard two years and are monitored throughout that process or that period for response and can have a best response documented anytime during that period. We already account for pseudoprogression in a way which we believe the FDA is fully happy with. I think that the principal difference is the rules that we have for pseudoprogression and treatment beyond progression are pretty much the industry-standard rules that we see across a large number of trials that we run here at Oxford. I think the big difference is that it is one of experience. We've treated a large number of patients in this program, and if you compare it to true progression versus pseudoprogression for, say, a combination of ipi/nivo and melanoma, we talk about it a lot. We see it rather less often, and for most patients whose lumps get bigger on ipilimumab/nivo, the reason they're getting bigger is they're not responding to the therapy. It's the occasional patient who is a late responder, and it's a true pseudoprogression. What's been striking throughout this program has been right from the get-go, the number of patients who've had their best response after completing virotherapy, and also the proportion of patients with an initial flare who then go on to get clinical benefit. Which does mean that we are able to be much more aggressive than perhaps I would choose to be with ipilimumab/nivo because I think the chances that this turns out to be a pseudoprogression are really very much higher. I can't put a quantity on that, and I apologize for that, but it's not something that we've tracked formally within the data. Our fellows only rotate every nine months. They start slightly cynical about this notion of pseudoprogression, and they leave us and believe it, and I think that's compelling. This is also why it's sort of important why investigators get experience with our approach, because an investigator who, for example, had only treated, this was their first patient that it was, saw this sort of increase may not be motivated to continue, whereas an experienced investigator who's treated a number of patients and seen good responses in them knows that it's worthwhile to persevere. This lady has ended up in a very good place. Experience is very important to learn about what to really expect for your patients with this type of therapy. We've got another question for Dr. Middleton. For the rapidly progressing non-melanoma skin cancer patients, is RP1 still the most promising approach you have? Would you consider adding some form of chemo to slow the tumor down and give IO a chance to get going? I think that's a very sensible suggestion. It's a shame Professor Harrington's not here because he's really the expert in non-melanoma skin cancer and has treated the majority of patients. I think to answer the first part of the question, it's very hard to get past and very impressive complete response rate in this cohort. Yes, I do think this is the most promising approach we have. What the last four patients have taught us is it's not a panacea. There are limits to what can be achieved, and we will need to think more creatively about how we set the circumstances in which RP1 can do its best work. I think chemotherapy is certainly an option, although it's not a terrifically chemo-sensitive tumor. Those patients were patients, at least a number, who have already failed prior chemotherapy. They're not patients who haven't already had everything thrown at them. Obviously, we did talk about earlier combining RP1 with chemotherapy as well, which we think is a potentially promising approach. Those patients already had chemotherapy and not benefited from it, at least two at the max. If we're stating the obvious, then obviously what really ought to happen is that those patients are treated early in their disease course with a type of regimen that involves an oncolytic and a checkpoint blockade drug. We would have a fair number of those patients who never get to that stage. Yeah. Obviously, as Philip was saying, it takes quite some time for tumors to get to be this sort of size, and if there were a known to be effective therapy available for those patients, they should not really have waited to get to tumors of this size before they were treated. One would hope in a real-world population post-approval that the patients wouldn't have tumors of this size but would be treated far earlier, and hopefully cure them much earlier and mean they never get to this rather nasty spot in their life. Questions on RP2. For RP2 plus Opdivo, were you surprised to see a lack of PRs with the PD-1 in nine patients? Can I just quickly answer that? For any patient who'd be eligible for anti-PD-1 in the combination with RP2, they have to have had anti-PD-1 first. It's a Phase I population who've failed all available standard of care. The only patients who wouldn't have had anti-PD-1 are tumor types where anti-PD-1 is not approved. We didn't enroll, for example, any melanoma patients who haven't had prior anti-PD-1 or any other tumor types where anti-PD-1 is approved and they haven't had it. Another RP2 question. How do you view the response dynamic from RP2 and nivo combo? For example, post outright response, post stable disease or progression? I think it's too early to say, but based on the data that we've presented today, if you look at the spider plot, the swimmer plot, which outlines the individual patient experience, which is all that we can really talk about at the moment, the dynamics do not look significantly different from RP1, where we have more mature data. The key issue there is I don't know of anything else out there at the moment, if you look at RP1, where a third of patients who've progressed with PD-1, you can get an objective response. Again, that's better than tebentafusp and some of the other agents that I've been involved in developing in this space over the last five, six, seven years. To come back to the RP2 question, the early indications are not of anything that's substantially different. It's not what I expect it to be. If you think about what is different between RP1 and RP2, it is essentially the CTLA-4 inhibition, and we know that the kinetics of that are relatively slow and more compared with chemotherapy or targeted therapy, and therefore it would be something of surprise if it speeded things up. This slide here just reminds you of the tumor types which were involved in the RP2 plus nivo combination part. As you can see, they're a mixture of quite rare tumor types. Generally, they really are a phase I population. They failed everything which they could have under standard of care. It is a salvage population. Those with melanoma, uveal melanoma, head and neck, have already had anti-PD-1 before coming onto the trial. Obviously the other tumor types, anti-PD-1 is not approved because it's either not been tested or known to not be effective. We have a question: what are the considerations for deciding whether you will be advancing RP2 or RP3 in any setting? We definitely think that the RP2 data, both as a monotherapy and in combination, is extremely promising. If we didn't have RP3 following along rapidly behind, I think we'd be very motivated to enter broad development with RP2. However, as we do have RP3 following quite rapidly behind, we think it is sensible to gather additional data with RP2 and the initial data with RP3 before deciding which to push the button on for broad future development. There is a sort of interim potential approach, which is progressing RP2 in 1 indication, for example, uveal melanoma where we've clearly got a signal, and then reserving everything else for RP3. Exactly what we do will depend on the data as it accumulates over the rest of this year and early next, which will tell us whether we should do everything with RP3 or do most things with RP3 and just a smaller number of things with RP2, for example, or any combination thereof. It's all going to be data-driven, and we'll follow the data. If RP3 really has properties we really like, the intention would be to do most things going forward with RP3. Another question here: Can you elaborate on how you're thinking about a registrational development path for patients with liver metastases? That really is too early at the moment to further comment on. We do have some internal things we've been thinking about, but it's too early to comment on publicly at the moment. Question. It appears like persisting through pseudoprogression is providing good outcomes. How consistent are the protocols in allowing for this persistence when there seems to be initial progressive disease? All of our protocols have exactly the same wording, so it's entirely standard across everything we're doing. Just to reiterate the point made earlier, what you write in the protocol is very different from what you train the investigator, and the value of experience there. All protocols carry roughly the same language around pseudoprogression these days. It's very much about the experience with the agent, and I think the power of anecdotes, either somebody else's or when an investigator first sees for themselves what happens by persisting, that drives this. I don't think there's a way around that. It's about choosing investigative sites carefully. It's about picking people with the relevant experience. I think also, the right patient and patient population will be greatly helped because the nature of this early part of the program is that patients don't have huge numbers of options when they come off the program. Therefore, it's not that they're going to come off because they're attracted to some other approach. They are therefore willing to persist. I think it's also about communication. When I say communication, I mean with regard to running the trial, such that we do have investigator meetings, such that the investigators are hopefully properly collaborating together and all as a group, aware of the group experience. Even if they themselves have only recruited one or two patients and haven't necessarily seen this sort of thing occurring as yet, or indeed haven't recruited a patient at all, the group experience is communicated, such that the group motivation is there. Another question coming in. Given the desirable investigator experience with RP, what are the company's plans to get U.S. physicians and KOLs involved in trials? The protocols are active. The RP1 protocols are active globally, in the U.K., in Australia, in Europe, and in the U.S. We have a substantial number of U.S. sites participating in the SURPASS study and participating in IGNYTE RP1 trial, including the melanoma 125-patient cohort. They are delivering substantial numbers of patients into those trials. With RP2 and RP3, we've always taken the approach at Replimune, due to our relationships with investigators and history, that we've conducted the initial Phase I part of trials in the U.K. in collaboration with particularly Mark, The Institute of Cancer Research, Royal Marsden in London, and now Joe Sacco in Liverpool, and then moved out more globally, in particular in the U.S., as we get past Phase I. The same would be intended to be the case with RP2 and RP3. The liver mets program we've been describing or in an early outline, would be conducted globally, particularly including the U.S. Rob, can you talk about the advantages of using CD40 and 4-1BB over other co-stimulatory agents? Yeah. I think the greatest advantage of 4-1BB and CD40 over the other co-stims, which include things like OX40, GITR, ICOS, HVEM, while those other pathways are clearly very active in mice, the human experience with those other pathways has been really rather disappointing. CD40 and 4-1BB are also active in mice, but not any particularly more than OX40. There is human data which suggests that targeting CD40 or 4-1BB in humans really is a worthwhile thing to do in humans. The reason we chose them was based on not only the fact that we could get very good outcomes in mice, but also in contrast to the other things we also tested, which worked well in mice. Antibodies, agonistic antibodies developed by others have shown promising early activity, although in some cases compromised by toxicity caused by the systemic administration approach of the antibody. We obviously aim to retain the activity, but get rid of the toxicity by delivering the activating ligand directly into the tumor where it's really needed, and limiting the systemic exposure to a very low amount. What is the likelihood of generating CRs with visceral tumors by RPS-EFs toggle effect? We have demonstrated CRs in visceral tumors following administration of RP1 into superficial tumors. We do see that. Those six patient examples, as Rob previously presented, include examples where the liver's been injected, and you're seeing abscopal effects in nodes in the abdomen. You're seeing abscopal effects in the spleen after injection in the liver with complete resolution of disease in the spleen, and as Rob also refers to, resolution of disease as far away as the lung, where a metabolic complete response has recently been declared in patient 6. This patient number 5 is specifically a patient who had a lesion in the thigh, which was injected, and also these lesions in the liver, which completely resolved. These are systemic responses. We have a question here. What data do you need to be able to move into earlier lines of treatment in larger cohorts? When do you anticipate having this? In CSCC, we're already conducting a registrational study in the first-line setting, or at least in the patients are eligible who haven't had any prior therapy. They just need to be not eligible for radiation or surgery. We're already in the first-line setting there. For us to get earlier in disease courses in general, it will be starting to combine with whatever the standard of care is in the first-line setting, whether or not that first-line standard of care happens to be an anti-PD-1 agent. One can also think further down the line to particularly neoadjuvant approaches in various diseases, which is something we're also extremely interested in. A combination of the two, really. What are your thoughts on evaluating RP2 for second-line PD-failed head and neck squamous cell carcinoma? We certainly think that that's a potentially attractive indication for us. Also upfront combination with chemoradiation in a neoadjuvant approach is also a potentially attractive indication in head and neck cancer. We've certainly got interest from investigators to test RP2, particularly in head and neck cancer, and we'll see where that interest leads. Next question. Do the costims built into RP2 and 3 play a role in the abscopal effect, or do they only play a role in the injected tumor? The aim of expressing those is to increase the systemic immune activation and therefore the abscopal effect. We would expect would have more limited impact on the injected tumor. The idea is they're expressed in the tumor and provide the costimulatory signals to maximally activate T cells to provide a systemic army of T cells to systemically treat disease. The aim is to increase systemic effect, not local effect. In actual fact, if you look at our mouse data, you see that adding in the CD40 ligand, 4-1BB ligand, or indeed anti-CTLA-4 has a much greater impact on uninjected tumors than it does on the increased activity in injected tumors. We have another question on RP2. With RP2, are you seeing a deepening of responses over time in either the monotherapy or in the early PD-1 combination data? Mark can also further comment, but if one looks back at this slide again, absolutely we are. As I said earlier, they got the short poke course of five doses of single agent RP2. At the first scan, this patient was a stable disease, which then deepened to a partial response, which has been maintained down to the present day, and as Mark said, has recently had a PET scan indicating no metabolic evidence of active disease. Similarly, this patient at their first scan after completing the course of RP2, the patient had a stable disease, which then deepened to a good partial response. Unfortunately, as Mark indicated, he succumbed to his disease at roughly 15 months. This third patient had a PR at their first scan which deepened to a complete response, which is still ongoing in a very stunning fashion. I was talking to Kevin Harrington yesterday, who's the investigator, and this patient really is a true miracle as compared to what would be expected if he was progresses otherwise. In all these three patients, responses deepened over time and after completing the course of RP2 treatment. Great. Maybe time for a couple more. One coming on RP1. Does RP1 reinitiation always involve a new lesion? When it worked, was the lesion a deeper lesion than the original? How many lesions are generally injected? We only have a very small number of patients so far who have had reinitiation. As I said, in most cases, just the first course of eight is about right. I believe it's four patients who've been reinitiated with RP1. As I think about it, I haven't got it off the top of my head. They have so far been one patient who had a local recurrence in the area of the original tumor in the nose, which is responding to that reinitiation of that local recurrence. The second was the local recurrence in the thigh, the example we showed, which is the site of the originally injected tumor. The patient additionally had tumors in the groin and in the lung, which responded in the first place and have not further progressed. The only site of relapse actually was the initial tumor in the thigh, which was reinjected and responded. That's two of them. The third patient is Mark's patient who had disease in the shoulder, as far as I remember, who initially achieved a very durable, stable disease. That began to progress and reinitiation occurred. Now they're now down to a nearly a partial response, better than their first response. It's again at the local site of the initial disease. The last patient's a patient who had lots of lesions in their leg, who achieved a very good and durable partial response, but whom reinitiation was pursued, not because of any sort of relapse, but to try and convert that patient into a CR. That patient does seem to have further benefit from that second course. There hasn't been a case where there's been a distant relapse which has been reinitiated. It's actually only been very small local relapses, which so far have been kept under control by the reinitiation. It's a mix of new lesions or lesions that have arisen where previously they've gone and then come back, and then a couple of patients where there's always been something to speak to the original question. Yeah. I was talking about RP. With RP2, we've had a number of patients who've had some new lesions appearing after the initially injected lesion had gone away, actually before the full eight had been used, and then those new lesions were injected and response had occurred. Final question, when do you expect to provide more specific timelines for CERPASS and IGNYTE pivotal readouts? Philip, can answer that? Yeah. Our current guidance is quite broad with the primary readout within the 2022 time frames. As we move into the second half, it's appropriate to give a more granularity on that, and we will do so within the next three months or so in terms of giving guidance on when we expect a full enrollment and when we expect the primary readout, probably at the next quarterly release. Just before turning it back to you, Philip, if we didn't answer any questions, we will try to get to those in the future on future calls. We'll turn it back over to you, Philip. I just want to thank everyone again for their time this morning. We look forward to, towards the end of the year, giving more granularity on this, particularly this phase II program in liver, which will involve prevalent tumor types like colon, breast, and lung. Obviously look forward to a future update as well on the data side around the year-end. Just like to thank Mark for his participation and again, everyone for their time. Good time to close out the meeting. Thank you.