Welcome everyone to the 39th Annual JP Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by Cesar Romero and Matt Bannon from the team. The next presenting company is Replimune, and speaking on behalf of the company, we have CEO Philip Astley-Sparke. Before turning it over to Philip, I just wanted to remind everybody on the webcast, if you'd like to submit a question, please use the Ask a Question feature in the portal, and I'd be happy to ask a question on your behalf. With that, I can pass it over to Philip. Thank you, Anupam. Safe harbor on slide two and starting on slide three with the Replimune overview. Replimune was founded to realize the full potential of oncolytic immunotherapy. Our products are designed to maximally activate a systemic immune response against a patient's cancer, and we believe that our programs will become the second cornerstone of immuno-oncology. RP1, our lead asset, principally targets immune-responsive tumor types and having generated strong data sets in PD-1-naïve cutaneous squamous cell carcinoma and anti-PD-1 failed melanoma. We have two registration studies ongoing in those settings. We also are pleased to announce that we hope to this quarter, have a further study with RP1 initiate in lung cancer. RP2, RP3 are intended to treat less immuno-responsive tumor types and following a generation of strong RP2 single-agent data in heavily pre-treated patients with immune-insensitive tumor types, the combination phase, the phase I study with Opdivo, is now enrolling. We also announced last week, I was very pleased to announce that RP3 is also now in the clinic, and dosing has commenced in single-agent portion of the phase I study. We have brought manufacturing in-house. Our commercial scale manufacturing facility is now fully constructed and operational, and GMP production is on the rise to deliver with $493 million estimate on the balance sheet as of the 31st of December, funding us into the second half of 2024. What is a reminder of oncolytic immunotherapy? It's the use of viruses that replicate in tumor cells and destroy them, but do not replicate in healthy tissue. On injection into a tumor mass, the tumor mass is invariably either completely or partially destroyed, and as the virus rips through the tumor, the neoantigens within are exposed to the immune system in an optimal environment of necrotic cell death. This is a major immune danger signal, attracts antigen-presenting cells to the site that internalize those escaped neoantigens, drain to the lymph nodes, where they prime T-cells to destroy uninjected deposits throughout the body. It's a dual mechanism of action, direct viral-mediated tumor cell lysis, followed by the engendering of a full systemic immune response. There are many different viral species being used as oncolytics. We use the herpes virus. We believe the herpes virus to be an optimal species for oncolytic use, it being highly lytic and inflammatory and having high carrying capacity to be able to carry in multiple immune-stimulating proteins into the tumor microenvironment to further amplify the immune response. Within the herpes field, not all constructs are created equal. Our construct is a new clinical isolate that's been deliberately selected after a comprehensive screen of 30 or so isolates and picked for its lytic ability. Then, from all of our products and part of our platform, we express a fusogenic glycoprotein from the gibbon ape leukemia virus, which essentially increases the lytic and immunogenic potential of the construct tens or a hundredfold. These aspects are designed to maximize antigen presentation or so-called signal one. We then further express immune-stimulating proteins from this backbone designed to maximize T-cell co-stimulation of the antigen-presenting cell T-cell interface, so-called signal 2. With RP1, we express GM-CSF, RP2, an anti-CTLA-4 antibody, and RP3, in addition to anti-CTLA-4, the ligand CD40 and 4-1BB, which have pleiotropic effects and also induce inflammatory cytokines. We do believe this is the most practical and comprehensive way to activate a systemic immune response against a patient's cancer. In terms of practical, it's an off-the-shelf product, simple to produce and relatively cheap to produce. It is also a relatively well-tolerated modality. On the efficacy side, it is effectively a pan-universal neoantigen vaccine, not confined to one or two neoantigens. If you're using the right viral species like herpes, you're triggering innate immune system pathways, and through the necrotic cell death created through the virus, you're quickly bringing in the adaptive side of the immunity. Further, through expressing these various immune-stimulating proteins, you can layer in multiple additional mechanisms of action. A quick recap of our pipeline. As I said right at the beginning, we have two potential registration studies ongoing in PD-1 failed melanoma and cutaneous squamous cell carcinoma, having generated strong data sets in those settings. We do also have a study ongoing cohort in the MSI-high cancers, colorectal cancers predominantly, and as I mentioned, about to start a cohort in lung cancer. Switching to RP2, RP3. We've seen very compelling single-agent activity with RP2, and RP3 is now in the clinic, and we're giving considerable thought to indication prioritization, where to place our bets in terms of later-stage development in immune-insensitive tumor types. Our lead indication at the moment is cutaneous squamous cell carcinoma. We have several studies ongoing in this setting. Not as well known as melanoma, the minimum addressable population is equivalent in terms of number of deaths. Up until two years ago, it was largely an unmet need, but PD-1s, anti-PD-1s are now approved, Libtayo and KEYTRUDA, giving response rates ranging from the mid-30s to 50%, but still very low complete response rates, on label, single digit. Our study, our potential registration study, the CERPASS study, is in 240 patients where we're comparing RP1 plus Regeneron's Libtayo against Libtayo alone. This is a cost-sharing collaboration with Regeneron, and the primary endpoint is overall response rate. We powered the study to show a 15% delta improvement such, for example, if the Libtayo arm got 40%, we would win in the mid-50s. Moreover, from what we've seen to date and what we know about the modality, we expect to show a two to 3x improvement in the overall complete response rate, which more closely correlates with survival. To date, the data we reported at CSCC has generally waxed and waned slightly, basically delivered a 80% response rate and a 50% complete response rate in CSCC. Those responses have been very durable in nature and obviously a very high rate of actual complete response, very deep responses. We've seen responses both in systemic disease and in advanced local regional disease, which is actually a highlight in this indication. It's actually the primary driver of mortality, it being principally a disease of the head, neck, and the scalp, and invades vital structures. This is an example of a full systemic immune response whereby a patient presented with large lesions in the neck, retroperitoneal node, and extensive mets in the bone in the spine. We injected the one area of the neck with a priming dose of RP1 as mono, and the tumor flattened and started to resolve as an uninjected one on the other side of the neck, but then layered in anti-PD-1, and by 16- 24 weeks, the extensive disease, as shown by the CT scan in the neck, had resolved, as had the retroperitoneal node. The bone mets looked to be static, and they were confirmed to be metabolically inactive one year later, and the patient was declared as a complete responder. These were the most recent patients that we had gave an update on in October over and beyond what we had disclosed last June. The top patient there presented with a very nasty ulcerative mass on the foot and tumor burden in the groin area, which was injected. Those lesions resolved. The uninjected lesions on the foot started to resolve, and then additional injections were made around the periphery, and this patient continues to improve. A pictogram tells a 1,000 words. Overall, our responses are very durable in nature, now out around 600 days. We've only ever had one patient progress, and that patient was in response for quite some time. The responses are, as I said before, very deep and durable in nature and give us high confidence that we will meet with success in our potential registration study underway. Switching to anti-PD-1 failed melanoma, which is still a real unmet need. Majority of patients, despite the advances, anti-PD-1 will become primary or have acquired resistance to that therapy. When they do, treatment options are limited. The response rate to second line of anti-PD-1 for patients that have truly progressed, confirmed through two scans, is very low, mid-single digit at best. We have dosed 16 patients in cutaneous melanoma that have failed anti-PD-1 in a very late-stage population of 87.5% stage 4 M1b/M1c advanced visceral disease. As of last October, when we last had a data cut, nine of these patients have shown some evidence of clinical benefit, as defined by at least stable disease with evidence of anti-tumor activity, of which five were full responders, one CR and four PRs, four out of these five having failed both anti-PD-1 and anti-CTLA-4, giving a current response rate of around about 31%. A further patient is an ongoing surgical CR out to 12 months of disease having not returned, and a further patient remains on study with stable disease. To give some examples in this setting, this first patient at the top was ipi/nivo failed melanoma, extensive visceral disease, fairly progressing when coming on to treatment. We injected a liver lesion shown in the red circle, which has almost resolved away at the last data cut. You can see the uninjected lesions in the liver and the spleen have completely resolved away, and you can see resolution of a lower mass there in the lung and a reduction of a very large mass in the top back box of that CT scan. The bottom patient had a very large groin lesion, was essentially homebound and wheelchair-bound, and also had extensive mets in the groin nodes, the lung, and suspicious bone lesions. We, again, only injected one mass in the groin area, which resolved away, as did uninjected disease in the lung and other nodal disease. The bone mets look static. It's not actually clear this patient has any disease at this point in time. Not an official CR, but what we would call a clinical CR. Very interesting biomarker data from this patient. On the right there, in the immunohistochemistry, you can see a classic mechanism for primary resistance to anti-PD-1, which is T-cell exclusion from the tumor microenvironment. After layering in our regimen, that immune tolerance is broken and the profound clinical benefit is evident. Again, these plots tell 1,000 words. Very durable responses in melanoma, generally, not just in anti-PD-1 fail, but in the other melanoma types we've tested in and got responses, including mucosal and also in PD-1 naive disease. Again, all but one patient that's ever gone into response remains into response out now beyond 450 days. The responses that we are engendering are uniformly very durable in nature. The spider plot there, I think is of interest that the red lines are PD-1 failed patients and the green lines are PD-1 naive, and they pretty much overlap, which I think really shows the potential of RP1 in the PD-1 failed setting. Again, we have high expectations that we will meet with success in our potential registration expansion cohort of 125 patients, and we will be discussing that study design with the FDA towards the end of the quarter. Switching to RP2, which is RP1 that in addition expresses an anti-CTLA-4 antibody. This isn't just limit systemic toxicity of anti-CTLA-4. There is a strong efficacy rationale to marry up maximizing signal one and antigen presentation on the MHC through the lytic action of our virus with ensuring that there's no negative feedback loop through the CTLA-4 pathway. The single agent data with RP2 showed that similar side effects to RP1, really mainly erythema at the injection site and febrile reactions. This modality is generally very well tolerated. Patients can often go back to work following treatment the next day. We also saw compelling single agent responses in immune insensitive tumor types, including mucoepidermoid carcinoma, uveal melanoma, and esophageal cancer. We saw a further interesting patient, who won't be an official responder because it did progress, but after progression, non-target lesions started to resolve. This is a patient with a microsatellite stable colon cancer, another immune-insensitive tumor, major unmet need. This patient initially presented with a high disease burden in the lung, spleen, liver and one other site. Again, the data cut-off of October, these responses are all deep and durable and ongoing. In terms of the actual patient examples, mucoepidermoid carcinoma is a salivary gland cancer, untreatable checkpoint blockade drug does nothing. This patient would have had a very bad prognosis leading to death. At the moment, it's an ongoing, durable, complete response. Over four months, the nodal disease, the superficial disease have resolved away and was confirmed as a CR eight months through PET showing the tumor. No metabolic activity. This is a response in uveal melanoma, ocular eye cancer, melanocytes in the eye, where the eye is often surgically removed, but often and typically metastasizes to the liver, which is often actually the only site of metastasis. Once metastasized to the liver, one year survival is 10%-15%. It's generally a fairly immune-insensitive tumor, single percentage response rates to single agent checkpoint blockade, a little bit better maybe in the teens in combination. Regardless, this patient had failed ipi/nivo when coming onto our study with extensive liver mets. We injected the liver lesion in the red circle, and you can see that's nearly resolved away. You can see uninjected ones in the yellow circles having either completely resolved away or also resolving away. This patient continues to improve at each subsequent scan. This is an esophageal cancer patient treated with single agent RP2, came on a study having failed anti-PD-L1, a kinase inhibitor, and four rounds of chemo. Actually had more than one liver lesion. It's not a particularly good scan. You can see that lesion resolving away that was injected and abscopal effect in the abdominal lymph node. That's the summary of our clinical data. Do also want to highlight, as I said at the beginning, that we have completed the construction of our manufacturing facility. We only broke ground at the time of the IPO two and a half years ago. I think it's testament to really the experience of the team that this facility is already operational and having completed tech transfer from the contract manufacturing organization GMP manufacturing is underway, and we have had a positive meeting with the FDA in terms of comparability to this contract material, the suite of tests that we'll have to run in order to use this as launch material. My final slide is really a summary of news flow over the next two years. In 2021, we expect to present in some entirely new datasets over and above what we have presented in the past, which is predominantly focused on phase II datasets in melanoma and cutaneous squamous cell carcinoma, as well as phase I all-comers datasets. Over the next year, we'll have new defined datasets in PD-1 failed lung cancer, very much an unmet need. We've never dosed a lung cancer patient, but the reason why we decided to proceed with this is we have seen that we can inject lung mets from other tumor histologies and see effects both in the injected lung lesion and in uninjected lung lesions. We are intrigued to see how this cohort does over the course of this year. We also announced at the end of last year that we plan to go into the PD-1 failed setting cutaneous squamous cell carcinoma, which is kind of intuitive given the responses we've seen in anti-PD-1 failed melanoma and in anti-PD-1 naive CSCC. We have high expectations that our products will also be of benefit in this setting. We have talked about the past about CSCC transplant patients. These are patients that develop the disease after being immunosuppressed for organ graft transplants, and anti-PD-1 is contraindicated due to the risk of loss of graft. This actually gives us an opportunity to generate, in an ethical way, more single-agent data with RP1. The RP2 plus Opdivo part of the phase I study is enrolling and enrolling well, so expect towards the middle of the year to be able to report out data in that cohort. We're excited to have got RP3 into the clinic and should be in a position to report out single-agent data in the second half of the year. Of course, during 2021, we'll also have additional updates on all the studies we've talked about during 2019. In 2022, which isn't too far away now, we expect to have the primary readout from our two potential registration studies in PD-1 naive CSCC and anti-PD-1 failed melanoma, as well as the combination phase of the RP3 phase I all-comer study, and could also have obviously other readouts from studies we plan to initiate in the interim. We have a full indication prioritization analysis underway as we map out where we will take RP2 and potentially RP3 in terms of later-stage development and development with registrational intent. We're in a strong position in terms of capital, having cash two years beyond reaching, or hopefully reaching all these milestones, with runway into the second half of 2024. Thanks for that, Philip. Maybe if you want to introduce the broader team on the line, we can come in with the Q&A. Just a reminder to those on the webcast, if you want me to ask the question on your behalf, just send it through the portal. Yes. Thanks, Anupam. I'll introduce Rob Coffin, our President of R&D and Founder, Jean Franchi, our Chief Financial Officer, and Pamela Esposito, our Chief Business Officer. Great. Maybe we'll start out with RP1 and the phase II CERPASS study in CSCC. Maybe you can give us an update on how the enrollment curve is shaping up. I know the data's expected to be in 2022, but how we should think about the enrollment curve here. Sure. Rob? Well, we're not providing granularity on exactly where we are in enrollment. We are guiding that we're on track for the primary output in 2022. Which means that we need to complete enrollment of the trial around the end of the year, if a bit after. It would be expected, as with all clinical trials of any size, that the enrollment curve would be relatively hockey stick shaped, including as over time we bring on additional sites and countries which aren't immediately open at the beginning of the trial. It is the case, we have seen some effects of COVID on enrollment in this trial, which means we have taken the mitigating steps of increasing the number of countries and sites to complete the trial which will exaggerate that hockey stick shape. We're confident we'll meet the timeline as previously indicated. Got it. In CERPASS, I guess, what's your assumption for how the control arm performs? Libtayo? There's a wide range of single-agent activity there, I think in the mid-30s to low 50s. Is a 15% delta in improvement in ORR clinically meaningful in the eyes of physicians, and how are you thinking about CR rate differentiations? Obviously, as you say, there's a range of expectations for anti-PD-1 therapy. There's various different data sets out there. I do think whatever the control arm shows within that range or even slightly above that range, bearing in mind what we're already seeing in CSCC in combination with Opdivo, that we should have good confidence that assuming in combination with cemiplimab is similar, that we have the headroom to show the needed benefit from a statistical perspective. Discussion with both investigators, and in fact the FDA in relation to the design of the trial, indicated that the statistical objectives of the trial, which are a minimum delta, as Philip said, of around 15%, would be deemed to be clinically meaningful. However, as with all data packages, it's dependent on the totality of the data, in particular durability as well as response rate per se. Obviously increasing the CR rate will also be thought to be particularly clinically meaningful because CR is most likely to contribute to greatly extended survival. There again, from the data we have already with nivo, we are expecting to move from the low single to roughly 10% maybe range of CR at the time of the data cut, which would be expected for single-agent Libtayo to two or threefold that based on our current data with nivo. We think we have good confidence that we have a well-designed study which should easily enable us to show clinical benefit. We got a email portal question here on RP1. Could you comment if CERPASS and the PD-1 refractory melanoma studies ongoing are going to be used for registration? Certainly that's the intention. The CERPASS trial was designed with registration intent in the first instance and was discussed with the FDA on that basis, who have indicated support to the design, assuming successful and based on the totality of the data. The melanoma single-arm trial was set up with the intent of registration. While all our advisors indicate that single arm of a trial of that size with the expected efficacy hurdle or objective should be appropriate, as Philip indicated, we don't yet have FDA formal buy-in to that. We are having a Type B meeting within pretty short order to get formal buy-in to that design. Got it. Philip, in your presentation related to RP2, you mentioned multiple times that you guys are taking the process right now for indication selection. Maybe you could walk us through what the push-pull levers are and how you think about what could emerge as one or a few of the indications that get prioritized here. Sure. Obviously, we'll be predominantly data-driven. That's part of the reason why we expanded the RP2 plus Opdivo part of the phase I study from 12 patients to 30. At the same time, we are in conjunction with a consultant doing a full analysis, looking everything from a market potential to the size of study we have to run, what the endpoints might be, how long it might take to read out, what line we might be in, a real comprehensive analysis. That's the sort of framework answer to the question. To put a little bit of meat on the bones, we don't quite yet know what's going to bubble up to the top, but we do think it is of real interest that we have seen that in multiple tumor types, we can inject liver lesions and see the injected and non-injected ones in the liver and beyond respond. Obviously, there are many tumor types that metastasize to the liver, large tumor types, and treating those liver mets is particularly problematic. Got it. I am going to pass it over to Tess to ask some questions on RP3. Hey, guys. This is Tess. I know the RP3 program recently initiated. You got that off the ground. It sounds like we're going to see some data this year from that program. I guess, do you think you guys will follow a similar playbook as you followed for RP1 and RP2? Just remind us of what you're thinking of in terms of size and scope of data for that initial data set later this year. The RP3 phase I trial is really very similar, if not identical to the RP2 phase I trial, which has a dose rising phase, which is relatively modest in size, which goes through two dose rising level cohorts, which obviously would expand to larger cohorts if any DLTs were observed. After determining the RP2D based on that single-agent data, injecting RP3 into both superficial and deep tumors through imaging guidance. We will enroll a 30-patient cohort in combination with anti-PD-1 therapy. It has standard phase I inclusion criteria of all comers who've failed standard of care. If there were no DLTs and no cohort expansion, the numbers of patients would be similar to what we showed with RP2 in October. Obviously may be larger if there were any reason to expand the cohort. Okay. I think we're about at the time here, so just wanted to thank you guys for this productive session, and I hope you guys have a good rest of the conference. Great. Well, thank you for the invitation to the conference. Thanks, Anupam. Thanks. Thank you.