Welcome everyone to the 42nd Annual J.P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by my squad, Lauren Hall, Priyanka Grover, Malcolm Kuno. Our next presenting company is CytomX, and presenting on behalf of the company, we have CEO Sean McCarthy. Sean? Great, thanks, Anupam. Great to be here. Thanks very much to the JP Morgan team for the invitation to the conference. I will, in the course of the next 30 minutes or so, be making certain forward-looking statements. I refer you to our SEC filings. So today, in my presentation, I will review our multimodality Probody therapeutics pipeline, which is designed to address major unmet needs in oncology. Let me start with a brief company, company snapshot. We're a South San Francisco-based clinical-stage oncology-focused company, developing a pipeline centered on our unique and differentiated Probody therapeutics platform. The platform is designed to localize the activity of potent biologics, including T-cell engagers and antibody-drug conjugates, into the tumor microenvironment, increasing therapeutic index. We've spent more than a decade pioneering, researching, and developing this unique approach, and given the high level of strategic interest currently in ADCs and T-cell engagers, we see the company as very well-positioned as we enter 2024. Our lead programs are CX-904, which is a EGFR CD3 T-cell engaging bispecific Probody; CX-2051, which is an antibody-drug conjugate targeting epithelial cell adhesion molecule; CX-801, which is a Probody version of the potent cytokine interferon alpha-2b; and BMS-986288, which is a non-fucosylated version of the anti-CTLA-4 antibody ipilimumab, that has also been masked using our Probody technology. Our leadership in this field has attracted major partners, and we currently have ongoing relationships with Bristol Myers, with Amgen, with Astellas, with Regeneron, and also with Moderna. CytomX is in a financially strong position. We last reported end of Q3 cash for $194 million with cash runway well into the second half of 2025, and that excludes any potential milestones that we may earn from our existing partnerships, and of course, any additional business development that we may do over the next one to two years. We have a terrific organization, 120 employees, a very seasoned executive team with more than 200 years of collective biotech experience, and integrated R&D capabilities to support wholly owned and collaboration programs. Our vision is to build a long-term, multi-product, commercial-stage oncology company. At CytomX, we have developed a product design strategy that leverages our unique technology platform and optimizes target selection, ProDomain optimization, and effector function. The Probody platform is designed to localize the activity of potent biologic modalities into the tumor microenvironment, increasing therapeutic index, and we achieve this through adding a protease-activatable masking domain that we call the ProDomain to the underlying antibody. Our prior foundational clinical work with this strategy has achieved many firsts, and we have opened a broad field into which we have seen multiple new entrants in recent years. At CytomX, we are currently focused on a generation of product candidates that integrate key learnings in how to optimally utilize our Probody technology, progressively enhancing the probability of technical success. Our current lead programs focus on validated targets, specifically EGFR, EpCAM, interferon alpha, and CTLA-4, for each of which substantial potential remains to be realized by increasing therapeutic index across a wide range of solid tumors. By employing our masking strategies and fine-tuning the ProDomain, the mask and the protease cleavable substrate that confers tumor-conditional activation, we tailor our product candidates in preclinical studies to optimize therapeutic window. And since our Probody approach is so versatile, we can apply it to a multitude of biologic formats, and this allows us to select the optimal effector. For example, a T-cell engager or an ADC to maximize antitumor activity. Using this product design strategy honed over the last decade, we have built a multimodality clinical pipeline that's designed to address large areas of unmet medical need. So starting with CX-904, our EGFR CD3 Probody T-cell engager, the strategy here is to utilize EGFR expression as an address to localize T-cells to solid tumors. The opportunity here is broad applicability in EGFR-positive tumors, regardless of their mutational status, really more a function of EGFR expression across a wide range of epithelial tumor types. Moving to CX-2051, this is our Probody ADC targeting EpCAM. This Probody is optimized with a topoisomerase I inhibitor payload, a camptothecin derivative, and our goal here is to increase therapeutic index for EpCAM, which has been previously validated by non-systemic therapies... and the opportunity here is really enormous to focus on EpCAM-positive tumors, for which there are hundreds of thousands of patients with unmet medical need, including third-line or later colorectal cancer. CX-801 is our Probody, our first Probody cytokine. It is a masked version of the potent cytokine interferon alpha-2b. Our goal here is to use our masking Probody strategy to harness interferon alpha-2b's potent antitumor activity to preferentially impact the tumor microenvironment. This molecule is designed to be a cornerstone of combination therapy moving forward for a wide range of solid tumors. In each of these programs, we have carefully tailored the preclinical pharmacology of the program and the Probody, and we're really excited to now be translating this strategy into the clinic. As we enter 2024, our multimodality clinical stage pipeline is at a really exciting stage, and we anticipate several key milestones this year. CX-904 is in an ongoing Phase 1A study. The program is partnered in a global co-development relationship with Amgen, in which we share U.S. commercial rights. Dose ranging is ongoing in EGFR-expressing solid tumors, and we anticipate initial Phase 1A data in the second half of this year. These data will be reviewed with our partner, Amgen, and if positive, will lay the foundation for advancement to Phase 1B in 2024. Our newest clinical program, CX-2051 and CX-801, are set to enter the clinic in the coming months, with INDs very recently filed. And our fourth clinical program is the CTLA-4 Probody, BMS-986288, for which our partner, BMS, is currently running proof-of-concept studies in non-small cell lung cancer and MSS CRC, and data is anticipated by BMS to become available in 2024. So we have a really busy and important year ahead for CytomX. Let me now review each of our programs in further detail. Starting with CX-904, our Probody T-cell engager targeting EGFR and CD3. Now, the landscape has really made significant progress over the last few years for T-cell engagers in solid tumors. Of course, the initial breakthroughs in the field of T-cell engagers were really seen in hematologic malignancies, beginning with Blincyto, the CD19/CD3 program that's had a big impact in various hematologic tumors, and much progress continues to be made, of course, in hematologic cancer. In solid tumors, it's taken longer to see meaningful advances, but we are starting to see success, and the field, we believe, is at a really important inflection point. Tebentafusp in uveal melanoma has been the first approval of a T-cell engager for solid tumors. More recently, the really exciting data from Amgen at ESMO 2023 for the DLL3 T-cell engager in small cell lung cancer really caught everybody's attention. So terrific progress being made, and indeed, global leaders are highly active in this field, including companies with whom we have partnerships, such as Regeneron, Amgen, and Astellas. Indeed, we could probably add Merck to this list, given their acquisition of Harpoon announced earlier this week. So the field is making a lot of progress. However, we would say at CytomX that for this modality to really enter the mainstream in solid tumors, there are still significant challenges to overcome, and we do see this as an excellent area of application of the Probody platform. So, what are the challenges that we're looking to address and that we believe our technology can overcome at CytomX? Well, we know that Probody T-cell engagers are exquisitely potent agents, and the challenge with this potency is that their utilization thus far, for the most part, in solid tumors, has been limited by cytokine release syndrome and ICANS-type phenomena, which are a function of CD3 engagement in the periphery. Also, translating T-cell engagers to solid tumors has been challenging by virtue of the solid tumor antigen targeted by a T-cell engager is more often than not expressed in normal tissues. And given the incredible potency of T-cell engagers, we see on-target, off-tumor toxicities that limit therapeutic window. Our platform at CytomX is designed, of course, using our Probody strategy to mask antigen-binding domains. We believe that our conditionally activated Probody T-cell engagers are well-suited to retaining potent antitumor activity while having less systemic toxicities. We have a broad pipeline of Probody T-cell engagers, both ourselves and with our partners, as I've already mentioned, Amgen, Astellas, and Regeneron, and with significant retained commercial rights on select programs, including CX-904. This slide shows the optimized design of CX-904, which is a bispecific antibody targeting EGFR and CD3, where we've masked both the EGFR binding and the CD3 binding domain. EGFR, of course, is a highly validated target. We know a lot about EGFR. It has broad expression across multiple solid tumors. It has clinical validation across multiple modalities, including antibodies and small molecules, but it does have a limited therapeutic index due to systemic toxicities, including skin rash and gastrointestinal toxicities, that would be expected to be exacerbated in the T-cell engager mode, given the potency of this modality in unmasked form. CD3, of course, is a well-established T-cell engaging strategy for this type of bispecific, well understood, well-validated. But we've really had to optimize our masking, and we've leveraged customized masking across both EGFR and CD3 to optimize therapeutic window in preclinical studies, and we're now translating into the clinic. The broad market opportunity for EGFR for CX-904 is illustrated by this slide. There are hundreds of thousands of EGFR-positive patients with metastatic tumors across a wide range of tumor types that could potentially be addressable by CX-904. So this is a very broad app, potential application, of our technology. And again, just to restate that what we're looking to do mechanistically is to use EGFR as an address to redirect CD3-mediated T-cell killing of tumor cells. We're making good progress in the clinic with CX-904. We are in an ongoing Phase 1A dose escalation study in patients with advanced solid tumors with known EGFR expression. We did begin to backfill certain cohorts at the end of 2023, and we are on track to have initial Phase 1A data in the second half of 2024. As I've mentioned earlier, our principal goal with that data will be to sit with our partner, Amgen, in the second half of the year to discuss the data and develop and devise our strategy for Phase 1B expansion cohorts in specific EGFR-positive tumor types to be taken in and potentially anticipated in 2024. Moving now to CX-2051, our conditionally activated Probody ADC targeting EpCAM. I think we're all well aware of the tremendous progress in ADCs over the last several years. We really have seen remarkable steps forward for ADCs, not only in hematologic malignancies, but particularly in solid tumors, more recently, over the last 10 years. ADCs are really making a huge difference in coming earlier in treatment paradigms, beginning to replace chemotherapy in frontline settings, being effectively combined with checkpoint inhibition in various tumor types. And of course, this success, this clinical success, this impact for patients, has resulted in enormous strategic interest in this field, as evidenced by the Seagen acquisition by Pfizer and the ImmunoGen acquisition by AbbVie, and of course, a very active licensing environment at the moment for antibody-drug conjugates. Now, EpCAM is a very interesting target. It's actually one of the first epithelial tumor antigens to ever have been described decades ago, and it has been validated previously by antibody strategies. We know that local administration of anti-EpCAM toxin fusion proteins or EpCAM bispecific modalities can shrink tumors. But the problem is, because EpCAM is so broadly expressed on normal epithelial structures, these agents cannot be administered systemically. And indeed, efforts to administer antibodies or T-cell engaging bispecifics targeting EpCAM have not progressed beyond Phase 1 previously by others due to various toxicities, but principally due to gastrointestinal tox and pancreatitis due to high expression of EpCAM in those tissues. But if we can find a way to effectively target and drug EpCAM, there's incredible potential because the target is expressed so broadly on so many epithelial tumors. So at CytomX, we have developed CX-2051. This slide shows the optimized design of CX-2051, again, an EpCAM Probody ADC with a topoisomerase I linker payload. The target has a broad expression profile, proven activity with localized therapy, but a limited therapeutic index that requires masking or improvement using our technology. The payload in this case is a next generation camptothecin that we've licensed from ImmunoGen. It has a linker payload that has been optimized for bystander activity and a drug-antibody ratio of 8. The masking strategy here has been optimized to drive a broad preclinical therapeutic window to enable us to translate this very exciting molecule into the clinic. And to our knowledge, 2051 is the only EpCAM ADC in development today, and something that we believe we can uniquely enable with our technology as a potentially first-in-class therapeutic. This slide shows the preclinical profile of CX-2051. This drug candidate shows DXd-like potency with substantially improved tolerability compared to the unmasked ADC. So on the left, you're looking at a comparison of a DXd conjugated version of our EpCAM Probody, versus the camptothecin payload that we have on 2051, and you can see very potent equivalent activity of these two agents. And so you should think of this as an equivalent, we think of this agent as being in the same general construct as in HER2, as an example. On the right-hand side, you can see the safety profile in cynomolgus monkeys. An unmasked anti-EpCAM ADC, shown in the top right of this table, is not tolerated at doses of 10 mg/kg. However, with the masked version of this ADC, we can treat monkeys with up to 60 mg/kg, sixfold higher doses. It's not indeed, it's not until we get to 90 milligrams per kilogram that we begin to see toxicity, and this is gastrointestinal toxicity, as predicted from the expression of the target in the GI tract. So we're really excited about the, the breadth of the preclinical therapeutic window that we have been able to achieve in our preclinical optimization, and we are moving into Phase 1 in the first half of this year. As I said, the IND has been filed, clinical strategy has been developed, and again, a bit like EGFR, there are hundreds of thousands of patients with high EpCAM expression across multiple tumor types that we know are sensitive to camptothecin class payloads, including lung cancer, gastric, colorectal, ovarian, and endometrial. And indeed, this target, we think of it in a way, as having pan-tumor potential, further down the road. Phase 1, our Phase 1 study is about to commence, and our goal, of course, is to rapidly demonstrate proof of concept in EpCAM, EpCAM-expressing tumors. In dose escalation, which will follow a Bayesian adaptive design strategy, we aim to quickly assess the safety and preliminary efficacy profile of CX-2051 in EpCAM-expressing tumors, including, but not restricted to, third-line or later colorectal cancer. Our goal will then be, in 2025, pending the outcome of our Phase 1 study, to move into dose expansion in specific EpCAM-positive tumor types, to really explore the broader profile of this very exciting drug candidate. Turning now to CX-801, which is our conditionally activated Probody cytokine interferon alpha-2b. Now, we're all aware of the enormous impact that checkpoint inhibitors have had in the across so many indications. However, significant unmet need remains, and this creates a very big opportunity for CX-801. IO-sensitive tumors are well established, but even in IO-sensitive tumors, response rates range from between 10%-50%, and most patients ultimately progress. So, there's incredible opportunity and unmet need here, even in tumor types that have shown strong responsiveness to checkpoint inhibition. And then, of course, there are many IO-resistant tumors or cold tumors, if you like, where single-agent response rates to checkpoint, inhibition is less than 10%, where significant opportunities remain. So, we see the opportunity for CX-801 as a potent immune modulator to increase the frequency and durability of responses in IO-sensitive tumors, and potentially to establish or restore efficacy in IO-resistant tumors. Interferon alpha is a very powerful cancer immunotherapy. Indeed, it was the first cancer immunotherapy to be approved several decades ago, and it has a dual mechanism of action, and we believe ideal properties to combine with PD-1 therapy. Interferon alpha is also mechanistically distinct from IL-2, IL-12, IL-15, and our view at CytomX is that this cytokine has been overlooked in many ways over the last few years. It has been approved previously for the treatment of melanoma, bladder cancer, and importantly and interestingly, even quite recently, the gene therapy, the adenoviral gene therapy, Adstiladrin, has been approved for localized treatment of non-muscle invasive bladder cancer in the BCG non-responsive setting. Indeed, the potential of this localized version of interferon alpha was really underscored recently by a major deal between Royalty Pharma and Ferring Pharmaceuticals, the current commercializing company for Adstiladrin, in which a deal valued at up to $500 million was struck for a royalty interest in this novel interferon alpha-based therapy. So again, we know that localized interferon can work. What we're looking to do at CytomX with our dual masking strategy is to advance interferon alpha-2b as a systemic therapy to unlock multiple tumor types. Now, ultimately, we see this as being a combination strategy. We know that, and this is work that's been published previously by Merck. We know that interferon alpha-2b has proven combination activity with PD-1. This shows published work from the Merck team on in melanoma, where you can see PEG interferon plus PD-1 showing a very impressive 60+% overall response rate. However, this combination is severely limited by significant incidents of Grade 3-4 adverse events to nearly 50%. So, our vision for CX-801, our masked version of interferon alpha-2b, is to have less systemic toxicity, better exposure, systemic delivery, increased therapeutic index, and most importantly, improved combination therapy opportunities. The design of CX-801 is summarized here. Again, the target, if you like, the cytokine, interferon alpha-2b, previously validated, high potential, previously approved in multiple tumor types, enhanced anticancer activity in combination with PD-1, and limited current use as a systemic therapy due to poor tolerability. The masking strategy here is particularly unique. We actually really took some time in the lab at CytomX to optimize this dual masking strategy, to really ensure that we shut down the systemic activity of interferon, to really mitigate systemic toxicity. So, we're using a dual masking strategy, where we have a peptide mask that blocks the ability of the cytokine to bind its receptor in the periphery and an Fc mask, and both of these masks are protease cleavable, removed in the tumor microenvironment, liberating interferon to do its job within tumor tissue. Just a little bit of a deep dive on some of the science, because I think this is really very, very important and meaningful. This is a snapshot of some of the data from our most recent presentation at SITC in 2023, where the data suggests clear synergy with PD-1 and enhanced tolerability in preclinical models compared to unmasked interferon alpha. Top left of this chart, you can see the efficacy profile in more than 25 experimental models that encompass more than 15 different tumor types. And you can see that at the combination of interferon alpha, masked interferon alpha plus PD-1 results in potent activity across most of these tumor types. And so this is a drug candidate that has potential across multiple tumors. The Probody interferon has the ability to inflame the tumor microenvironment. Shown on the top right, we see powerful induction in combination with PD-1 inhibition of inflammatory cytokines within the tumor microenvironment. We have substantially improved tolerability of the masked interferon in mouse models. This is the bottom left-hand table. You can see that the masked Probody interferon, we can dose up to 1,200 micrograms, whereas only 5 micrograms of the unmasked interferon is tolerated in mouse models. This is also reflected in looking in specific immune organs that you can see in lymph node and spleen, the unmasked interferon activates immune cells, whereas the masked version does not. Our masking here, our optimized masking, has done exactly what we need it to do, which is to clamp down and reduce systemic activity of interferon while maintaining intratumoral activity, as reflected in anti-tumor responses and activation of an inflammatory tumor microenvironment. Very excited to be moving this wholly owned asset into the clinic. IND has been filed. Phase 1 dose escalation will commence in the first half of this year, and our goal is to assess CX-801 as a monotherapy, again, using an adaptive Bayesian design to evaluate safety and potential evidence of clinical efficacy in Phase 1A. But really to move quickly into the combination setting, because we think this program is ideally suited to be a combination partner for checkpoint inhibition. So our timing will be to conduct Phase 1A over the course of this year and into 2025, and to initiate combination dose escalation in 2025. In the last few minutes, I'd like to just talk briefly about the role of strategic partnering at CytomX over the years. Now, business development has really been a strategic engine for our company and for value creation and for financing. We realized very early on in our company's history that given the breadth of our technology, that partnering was going to be an important part of our business plan to enable us to generate non-dilutive capital, but also to take multiple shots on goal and really invest heavily so we could very really deeply understand and develop this very unique technology platform. So we have existing partnerships with Bristol Myers, with Amgen, Astellas, Regeneron, and Moderna. They're all moving along very well. We've generated more than $500 million of incoming cash from these collaborations to date. We have more than 10 active preclinical collaboration programs, and importantly, we retain significant commercial rights on many of these, assets, and of course, have multiple near and long-term milestones, that we can earn. And then the last thing to mention here is that I think is particularly notable is our alliance with Moderna is the first collaboration that actually takes us outside of oncology. And so with Moderna, we're working in oncology, but also some additional therapeutic areas on mRNA-encoded biologic strategies. And we've thought for a long time that CytomX technology, that our Probody platform, has potential in other areas, where protease biology is dysregulated, and we look forward to making, continued progress with all of our partners, including Moderna, over the coming year. Now, our most advanced partnered program is the next generation CTLA-4 Probody with Bristol Myers. This is a Probody version of a non-fucosylated ipilimumab. Why is that important? Well, the non-fucosylation is designed to make Ipi more potent, and the potency, the increased potency derives from increased ability of the non-fucosylated antibody to drive antigen presentation within the tumor microenvironment. Now, what has been observed is, with CTLA-4, is that as you drive potency of ipilimumab, you also drive increasing toxicities. And so our masking strategy is designed to improve the therapeutic window for this non-fucosylated version of Ipi, and very, very pleased to see terrific progress at Bristol Myers over the last couple of years. This is now their prioritized next gen CTLA-4 program. They are running proof of concept studies in non-small cell lung cancer and in MSS CRC, and they are anticipating data in 2024. So really thrilled about the continued investment in that program by our partner, BMS. Let me close with the outlook and upcoming milestones. As I mentioned earlier on, CytomX is really entering a catalyst-rich period. 2023 was really a year of execution in the pipeline, getting ready to file two new INDs, which we did at the end of the year, executing in Phase 1A dose escalation for CX-904, and working closely with our partners across now more than 15 programs across the entire pipeline, partnered and unpartnered. So looking ahead, what can we expect? Well, with CX-904, we're on track to have initial Phase 1A data from dose escalation in the second half of this year, and that data will be used in order to sit down with Amgen and discuss our strategies for Phase 1B, which will be initiated in 2025. Moving to CX-2051, IND is filed, Phase 1 initiation in 2024 in EpCAM-positive tumor types, including CRC, in the first half of 2024, with initial Phase 1 data in 2025. And again, that's a wholly owned program. CX-801, the interferon alpha-2b Probody. IND is filed, Phase 1 initiation in solid tumors, in interferon-responsive solid tumors in the first half of this year, which will include melanoma, renal, and head and neck cancer. Again, with initial Phase 1 data anticipated in 2025. And then, as I just mentioned, BMS-986288, ongoing Phase 2 proof-of-concept studies with data anticipated in 2024, and we would anticipate continued updates on this program strategy from BMS in the course of 2025. With regard to our research collaborations, a lot of work ongoing across more than 10 ongoing preclinical research programs with potential research milestones achievable over the next one to two years that have not been factored into our cash guidance of second half of 2025. So thank you very much for listening today. We at CytomX are building for the future. We have a differentiated Probody platform. We have a robust multimodality pipeline that addresses large market opportunities and significant areas of unmet need in oncology. We have very high-quality partners. We're in a strong financial position, and I'm very proud to work every day with our extremely talented organization. So thank you very much for your time. I'll ask a couple questions here. For CX-904, I think the data were originally in the third quarter. You said first half of 2024, but now the guidance has been updated to the second half of 2024. What led to that delay? Yeah, that's right. So, we were working towards the first half, and I think, you know, as we've looked at some of the emerging data from Amgen and others in the... I think there's an emerging playbook for the development of T-cell engagers that—in solid tumors that we're beginning to see, that, you know, it can take some time, and it's important to give ourselves the time to generate robust datasets. Given that our main goal for 904 in 2024 is to have that dialogue with Amgen this year around our Phase 1 dose escalation dataset, and we felt that it would be in our interest to give ourselves a little bit more time to generate as robust a dataset as we can to have as full and complete a discussion regarding the initiation of Phase 1B in 2024–2025. Then maybe moving on to the CTLA-4 program with Bristol, you know, you've got proof of concept studies in multiple indications, and that data is expected in 2024. So what's gonna be the size and scope of the data update, indication focus? Yeah, we, we don't have tremendous visibility on, on the BMS program, at this point. However, if we look at clinicaltrials.gov, you can see that the program has become quite extensive. They, they now have more than 40 active clinical sites. They've clearly been investing in this program over the last one to two years. The, the clinical design on that, again, on clinicaltrials.gov, speaks to several hundred patients to ultimately be enrolled. And in the context of, CRC, the test articles are, not only, 288 and, Nivo, but also regorafenib, which I think perhaps gives some insight into, what they may be doing in this, Phase 2 setting. So, you know, we're gonna have to wait and see, as the year progresses, exactly what their strategy, trial designs, and data, has been. But we would expect the updates, based on the activity on ClinicalTrials.gov, if they do indeed come in 2024, to be quite meaningful. Question from the audience? Just maybe a final question from me, which is: What are the gating factors to starting the Phase 1 trials with 2025 and 801? Yeah, well, as I said, the INDs have been filed. It's gonna be IND clearance and moving as quickly as we can to get our first patients on study. So, the team is working extremely hard to achieve all of that, and we're on track to get both of these studies up and running in the first half and very much looking forward to it. All right. Thank you, Sean. Thank you very much. Thank you all for your time.