Hi. Good Wednesday afternoon, everyone. My name is Malcolm Kuno. Welcome to the 41st Annual J.P. Morgan Healthcare Conference. With me today is my colleague, Dr. Priyanka Grover, and we are both on Anupam Rama's team. You know, I'm fortunate to be able to present our next company, CytomX, today. On speaking on behalf of the company is Sean McCarthy, CEO. Take it away.
Thanks very much. Thank you very much. Good afternoon, everyone. I'd like to thank the J.P. Morgan team for the opportunity to present. It's a real pleasure to be here. Before we begin, I would like to remind everyone that during this call, I will be making certain forward-looking statements. Important risks of uncertainties are set forth in our most recent public filings with the SEC at sec.gov. In my presentation today, I would like to give an overview of CytomX business strategy and pipeline, including our outlook for 2023. It's been a very exciting few months for the company as we've successfully navigated a challenging 2022, and we've entered 2023 with considerable momentum.
In the quest for more effective cancer treatments, given the enormous medical need that remains in oncology, the research and development of biologic therapies for cancer has evolved to highly potent formats that include T-cell engaging bispecifics, antibody-drug conjugates, and of course, immunotherapies. These approaches offer powerful anticancer potency, maximizing their potential will require that we find ways to more effectively direct antitumor activity towards cancer tissue and away from normal tissues. CytomX vision is to transform lives with safer, more effective therapies. We aim to realize this vision for the benefit of patients by leveraging our Probody platform to create high-impact therapeutics that will localize the disease tissue, thereby reducing systemic toxicities and maximizing overall benefit. Indeed, we believe at CytomX that localization of biologics will be the future of this drug class.
Our expertise in biologic masking and our understanding of the tumor microenvironment has positioned us at the forefront of this field. Over the past decade, we have translated our leading science into broad clinical progress, having treated now more than 500 patients to date with Probody therapeutics, many of whom have benefited significantly. CytomX has developed the leading platform for localizing potent biologics to disease tissue by leveraging dysregulated protease biology. Probody therapeutics are masked, protease-activatable biologics designed to be unmasked in the protease-rich tumor microenvironment. Through our state-of-the-art protein engineering strategies, we're using our platform to address some of the biggest opportunities in cancer R&D today. We're doing this by creating conditionally activated versions of multiple biologic formats, including T-cell engagers, ADCs, and cytokines.
Since our early years, CytomX has pursued a consistent strategy focused on long-term company build around the Probody platform to maximize impact for patients. Our substantial investments to date have resulted in a deep pipeline of therapeutic candidates positioned to deliver significant near-term and long-term value. Our robust pipeline includes four clinical stage programs, and we expect to file two new INDs for wholly owned programs by the end of this year. As a core component of our business model, we have also leveraged strategic partnerships to extend the reach of our science, broaden our pipeline, and bring non-dilutive capital to the company. With our recently announced alliances with Regeneron and Moderna, CytomX now has six major partnerships.
As a result of the disciplined execution of our strategy, including a restructuring that we implemented in and completed in 2022, CytomX remains very strong, well-funded into 2025, and positioned to execute to key milestones over the coming months and years. Our broad pipeline of Probody therapeutics encompasses more than 15 active programs. Programs for which we retain full or partial commercial rights include CX-2029, targeting CD71, CX-904 targeting EGFR, CX-2051 targeting EpCAM, and CX-801, a conditionally active version of interferon alfa-2b. Our fully partnered programs include anti-CTLA-4 Probody therapeutics being advanced by BMS in phase II, and multiple programs across various modalities, now also including mRNA-encoded biologics with our newest partner, Moderna. In my presentation today, I'll cover our pipeline by modality.
Firstly, our expanding activities in T-cell engagers, secondly, our antibody-drug conjugate programs, and thirdly, our immunotherapy programs. Starting with our work and our expanding R&D activities in T-cell engagers. Now, of course, T-cell engagers, as we all appreciate, hold tremendous promise for the treatment of solid tumors. However, the very potency of this modality can lead to widespread activation of the immune system. This can impose constraints on therapeutic window. Localization of the powerful anticancer activity of this class of drugs could unlock enormous potential for patients by enhancing therapeutic window. CytomX and our partners believe that the Probody platform could be ideally suited to addressing this particular challenge. Our lead program in this area is CX-904, which targets EGFR and CD3.
This is a clinical stage Probody T-cell engager partnered with Amgen in a global co-development alliance. Of course, EGFR is a highly validated and broadly expressed cancer target, and we see compelling opportunities to leverage this target to localize anti-tumor T-cell responses preferentially to the tumor microenvironment. Our published preclinical data has shown that a localized bispecific EGFR CD3 Probody has a widened therapeutic window compared to its unmasked counterpart. These preclinical data led to the advancement of CX-904, and we're now well underway with phase I. We're making excellent progress in the clinic. We successfully treated our first patient in May of 2022, and we've now advanced through the initial single-patient cohorts, and we're actively enrolling patients into the 3+ 3 phase of this study.
The goal of our phase I work is to assess safety of CX-904 and to select doses for expansions in EGFR-positive tumor types. We expect to make considerable progress here during 2023. Staying with T-cell engagers for a moment, we continue to make great progress in our multi-target program with Astellas, in which CytomX retains U.S. co-development and co-commercialization rights on a select number of programs. We look forward to providing additional updates as the year progresses. Continuing with T-cell bispecifics, I'd like to spend a few moments giving some perspective on our recent alliance with Regeneron. This is the newest effort in the space of T-cell engagers. In November 2022, CytomX entered a multi-target R&D collaboration with Regeneron to discover and develop new bispecific immunotherapies.
Under the terms of the agreement, CytomX received an upfront payment of $30 million and is eligible to receive up to $2 billion in milestones as well as royalties on net sales. Of course, Regeneron has considerable efforts in this space of T-cell bispecifics, and both companies see opportunities to broaden the reach of T-cell engagers by utilizing CytomX platform to localize these highly potent agents to tumor tissue widening therapeutic window. This shared vision formed the basis of our discussions last year, leading to the deal we announced in November. Given Regeneron's acknowledged high bar for external innovation, this collaboration is yet another point of validation for CytomX technology and our scientific and platform expertise. We're currently launching this important new alliance, and we look forward to advancing paradigm-changing medicines in collaboration with Regeneron.
Moving now to the application of our technology in the field of antibody-drug conjugates. Of course, ADCs are an increasingly important class of anticancer therapeutics with many new drug approvals in recent years. Conventional ADC targets must be differentially expressed on tumor tissue relative to normal tissue. Otherwise, these potent agents will cause undesired side effects, thereby lowering their therapeutic window. At CytomX, we're leveraging the Probody platform to unlock novel ADC targets by localizing drug activity towards tumor tissue and away from normal tissues. It's important to note here that in Probody ADCs, they encompass masking of the antibody, but not the payload itself. We need to take this into account as we evaluate these agents in the clinic.
I'd like to focus first, here on a newly emerging, wholly owned CytomX ADC program, CX-2051, which is our conditionally active Probody ADC targeting epithelial cell adhesion molecule or EpCAM. EpCAM has been regarded as a high-potential oncology target for decades and has in fact been clinically validated by others. Our new program takes advantage of key learnings in our work to date on ADCs and also the translational cycle of bench to bedside, back to the bench, back to the bedside that we have been pursuing for decades at the company.
CX-2051 is tailored to optimize the therapeutic window for EpCAM expressing epithelial cancers by matching the target with payload mechanism of action and of course, also tumor sensitivity, and we've optimized masking protease cleavability, and we've selected for this particular construct a camptothecin derivative, a topoisomerase I inhibitor from the TCAM class as the payload for this program. The TCAM payload class has of course, shown really exciting clinical results over the last couple of years for ADCs, including ENHERTU and TRODELVY, and we really think this payload is an optimal choice for this target and for this program. We think EpCAM is a really great target for our platform. It's one of the most attractive targets that we've thought of to date, and one of its most attractive features is its prior clinical validation.
For example, the antibody toxin fusion Vicineum, which was recently developed by Sesen Bio, has demonstrated impressive clinical activity in non-muscle-invasive bladder cancer. However, the challenge is that drug has to be given through local administration because of its severe systemic toxicities. In short, efforts to generate systemic anti-EpCAM therapeutics have to date not been successful. CX-2051, however, has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer.
A few examples of the tumor expression profile of EpCAM are shown here, highlighting that there are many paths to explore with this exciting candidate, including very high expression in colorectal cancer, and we anticipate filing an IND for this new ADC in the second half of 2023. Moving now to our lead clinical stage ADC, which is CX-2029, a first-in-class conditionally activated antibody-drug conjugate that targets CD71, the transferrin receptor. Now, similar to EpCAM, CD71 has been regarded for decades as a target with great potential, but it presents really unique challenges for the development of anticancer therapeutics because of its widespread expression on normal tissues and its central role in iron metabolism. Essentially, CD71 is an undruggable target using conventional approaches.
However, we've proven through our previous phase I work, which has recently been published in Clinical Cancer Research, and in updated phase II results that we announced last week, that we can successfully target CD71 with our technology. We are the first to have reached therapeutically active levels of a CD71-targeted ADC in patients, as well as have demonstrated clinical activity in areas of high unmet need. Now CD71 is a high bar target, there's no question about that, and that's by design. We continue to learn from this work how to maximize the potential of CX-2029 and also, of course, our overall Probody therapeutic platform. We've now completed the phase II expansion stage of our clinical evaluation of CX-2029, and the study design is shown here. There were three parts to the study. Part A was a 3+ 3 dose escalation that I just mentioned.
That ranged from 0.1 mgs/kg to 5 mgs/kg and administered every three weeks on a Q3W schedule. This work has recently been published, as I mentioned. Beginning at 2 mgs/kg, additional patients could be enrolled into part B, a biopsy cohort, and part C encompassed the phase II expansion cohorts, where patients were treated at 3 mgs/kg again on a Q3W schedule. The phase II expansions included squamous non-small cell lung cancer, squamous head and neck cancer, and esophageal and gastroesophageal junction cancers. The esophageal cancer cohort included both squamous and adenocarcinoma histologies, enrollment is now complete across the expansion phase.
Patients enrolled into the expansion phase were heavily pretreated across all cohorts with a median of 3 prior lines of therapy, including most patients having previously received both platinum-based therapy and also a checkpoint inhibitor. Patients were not selected in this study for CD71 expression. Taken together, looking at the data now across the completed expansion phase, encouraging clinical activity was observed in tumors of squamous histologies with objective response rates ranging from 7%-21% and disease control rates ranging from 53%-67%. We've previously reported clinical signals for CX-2029 in head and neck squamous cell carcinoma, and in squamous non-small cell lung. We've recently been very interested to see another squamous tumor signal emerge, this time in esophageal cancer.
This slide focuses on our most recent data for squamous esophageal cancer, where the objective response rate was 21% and the disease control rate was 57%. 3 out of 14 efficacy evaluable patients had confirmed PRs, and 5 patients had a best response of stable disease. As of the reported data snapshot, 5 patients remained on study, including three confirmed PRs and two patients with stable disease. These patients, as I've already mentioned, were heavily pretreated, and interestingly, all responders had received a prior checkpoint inhibitor. Interestingly, CD71 has been implicated as a poor prognostic indicator in esophageal cancer, and we're excited to follow up on this new signal. The next slide shows the spider plots across all tumor cohorts in the expansion phase, I want to again emphasize here that these were unselected and heavily pretreated patient populations.
There are several things to note on this slide. Firstly, the responses can be durable, as you can see from the plots. Secondly, all responses observed to date have been seen in patients with tumors of squamous histology. No responses were observed, as you can see in the upper right-hand panel, in esophageal adenocarcinoma, which is an interesting control in this study, if you like, really again highlighting that this drug does appear to have particular activity in squamous tumors. We're gonna continue to explore this intriguing clinical activity to develop potential patient selection strategies. It's known in the scientific literature that CD71 actually is amplified in certain squamous tumors, and this certainly merits further investigation. Turning to safety for CX-2029.
Across the expansion cohorts, safety and tolerability remained generally consistent with our previously reported clinical results for CX-2029. Anemia was the most common treatment-related adverse event, with 76% of patients experiencing grade three. Referring back to the spider plots on the previous slide, across the expansion cohorts, it's notable that patients who tended to respond tended to respond fairly quickly, which is not unusual for an ADC. Investigators were generally able to maintain these responses and keep patients on drug through a combination of strategies, including dose reductions, dose delays, and transfusions. To summarize for CX-2029, we have successfully utilized the Probody platform to open a therapeutic window for an ADC targeting CD71 for the first time, highlighting the potential of our core platform technology.
Meaningful clinical efficacy has emerged in heavily pretreated patients with tumors of three distinct squamous histologies showing responses, including a newly observed signal in squamous esophageal tumors. Biomarker evaluation for patient selection strategies is ongoing. We also continue to evaluate anemia mitigation strategies as we learn more about how to best utilize this drug candidate in the clinic. We look forward to working with our partner AbbVie throughout 2023 to determine the next steps for this program. Moving now to cover our work in the cancer immunotherapy space. I'd like to start here with our emerging strategy in cytokines. We believe there's enormous potential to harness the powerful activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation. Our lead program in this space is a conditionally active form of interferon alfa-2b.
Interferon alpha is a powerful mediator of immune cell activation with, we believe, ideal properties for cancer immunotherapy if we can better target its potent activity. Interferon alfa-2b provides an orthogonal activity to IL-2, IL-12, and IL-15 in the Cancer-Immunity Cycle. It can kill cancer cells directly, leading to immunogenic cell death, and also stimulate antigen-presenting cells to activate T-cells. These properties combine to confer the potential for a conditionally active interferon alpha to potentially unlock checkpoint inhibitor refractory or resistant tumors. Our lead molecule for this program is CX-801, which is a duly masked interferon alfa-2b. In data presented at SITC in 2022, we demonstrated that CX-801 has a wide therapeutic index with an enhanced tolerability profile compared to unmasked interferon.
Our data have highlighted CX-801's preferential activity in the tumor microenvironment, as well as the potential for synergistic effects when combined with checkpoint inhibition. We believe CX-801 has the potential to become a unique centerpiece of combination therapy for a wide range of tumor types. We aim to rapidly advance this potentially best-in-class program towards clinical evaluation with an IND filing targeted for the second half of 2023. I'll wrap up my review of our broad and deep pipeline, with briefly covering our collaborative work with Bristol Myers Squibb on next-generation CTLA-4 therapies. CTLA-4 continues to be an important target and actually a foundational immuno-oncology strategy. CTLA-4 blockade does have a narrow therapeutic window.
Our work with BMS encompasses two clinical stage programs designed to broaden the therapeutic window for CTLA-4 therapy and to expand the utility of this important target. BMS-986249 is a Probody version of ipilimumab, which BMS continues to evaluate in a randomized phase II study in frontline melanoma. 249 is also being studied in several expansion cohorts. BMS also continues to study the non-fucosylated CTLA-4 Probody, which is BMS-986288, and this is in phase I. This particular strategy is aimed at enhancing the clinical benefit of ipilimumab by engaging antigen-presenting cells and delivering superior APC-mediated T-cell priming. We continue to be really excited to be playing such a major role in BMS's next gen CTLA-4 efforts, and we look forward to future clinical updates from these programs.
I'd like to return for a moment to our announcement last week of the latest accomplishment in our partnering strategy, which is our strategic alliance with Moderna. In this new collaboration, CytomX and Moderna will be bringing our platforms together to research and develop mRNA-encoded, conditionally activated biologics. CytomX and Moderna share a vision of investing at the intersection of technology and biology to transform the lives of patients, and this perspective is central to our new partnership. Under the terms of the agreement, CytomX will receive an upfront payment of $35 million, which includes $5 million of pre-funded R&D. CytomX will also continue to receive R&D funding for the collaboration and is eligible for up to $1.2 billion in milestones, as well as royalties on net sales. Additionally, Moderna has an option to participate in a future CytomX financing.
Moderna is our sixth major partner. We are thrilled to be entering this new collaboration to focus on opportunities in oncology and also in non-oncology therapeutic areas. We're particularly excited here to be moving into new areas with Moderna since we have known for a long time that the protease microenvironment is dysregulated in many disease conditions in addition to oncology. We've had a long-standing interest in developing our technology into some of these new areas. It provides a number of new avenues for us for R&D and for long-term value creation. Of course, Moderna's global impact has shown the enormous power of mRNA, and we look forward to working closely with our newest collaborator to bring novel mRNA-based therapeutics to patients with unmet medical needs.
I'd like to close here by reiterating the depth, the breadth, and the scale of our work at CytomX as we advance our multi-modality Probody therapeutic pipeline. With more than 15 active programs, strong partners, significant retained pipeline ownership, and an increasingly validated platform, our company has never been stronger, we look forward to making substantial progress over the next 12-24 months. To sum up and to focus on the year ahead, CytomX enters 2023 with tremendous momentum. We continue to lead the field of conditional activation, we and our partners see localization of potent biologics as a strategic area of R&D and oncology and increasingly outside of oncology as well. Looking to our 2023 outlook, this will be a year of focused execution by CytomX across both our partnered and our wholly owned pipeline.
For CX-904, we're highly focused on execution through dose optimization for future potential expansions. For our wholly owned pipeline, we expect to file INDs for two new next-generation wholly owned molecules. CX-2051, our EpCAM targeting ADC, and CX-801, our first localized cytokine targeting interferon alfa-2b. Additionally, in 2023, we do expect to make progress in our most mature collaborations, including determining next steps for CX-2029 in conjunction with AbbVie, and additional progress from BMS for the ongoing CTLA-4 programs. Lastly, we're really excited to be kicking off work with our newest partners, Regeneron and Moderna, and to also continue to make progress across all of our collaborative programs. Thank you very much for your time today, for listening and joining us here. I'm happy to now take questions.
Thank you, Sean. If you have been with us at Analyst Week, you'll know that there are a few ways to ask a question. You can email us or use our J.P. Morgan portal to submit your question. If you're feeling bold or spicy, you can borrow the microphone in the back there. Questions from the audience? Sean, can we start with CX-2051? What has to happen between now and the IND filing? What should we think about in terms of potential gating factors?
All the usual box checks for IND-enabling studies. We're making excellent progress with manufacturing scale-up. Of course, GLP toxicology and we're planning for the execution of the initial phase I study. We're, you know, very much on track with that and on track to get that IND filed second half of the year.
Excellent. If we look at CX-2009, how are your partnership discussions going and what are you looking for in a partner specifically?
Great question. To recap, CX-2009 is our CD166 targeted ADC, for which we had a readout in breast cancer middle of last year. We decided based on that readout to put that program on the back burner and pursue some partnering conversations. Those conversations are ongoing. We have no formal guidance regarding timing to a partnership for CX-2009.
Sure. Any questions from the audience?
There's a question at the back.
Oh.
Given the current difficulties in raising cash, how much of the solution will be, you know, bringing partners in for funding?
I didn't really hear the question.
The question was.
Given the current difficulties of raising, you know, cash in this market, how much of your future involves bringing partners in for funding, you know?
Yeah.
A lot of these programs involved-
Great. Thank you for the question. As I mentioned in my, in my remarks, you know, we've leveraged partnering over the years as an important component of our overall financing strategy. We finished Q3 last year with $194 million on the balance sheet, with these two new deals, we've brought in an additional $65 million into the company, which funds us comfortably into 2025. You know, we've always pursued this two-prong strategy for financing, tapping the capital markets when our equity cost of capital is where we feel good about it, and leveraging deals often when we, when we don't like right now. We'll continue to prosecute that strategy on a go-forward basis, and I'm confident we will continue to fund and finance CytomX as we always have.
Related to that, what's baked into your cash runway? You know, what's assumed and what's, like, definitely baked into it?
There's a lot going on in the pipeline. As I said, 15 active programs at the moment, including two in phase II. Now, Bristol Myers is funding fully the phase II work on CTLA-4 and the 2029 program where we've wrapped up the expansion phase. The key next step there for that program is to sit down with AbbVie and determine next steps. After we do that, per contract, the program goes back to AbbVie to fund the next stage of development with participation by CytomX, but that won't kick in until phase III. So for the next 1- 2 years, we're really looking at executing on 904, executing on the two new INDs, continuing a robust research effort.
We continue to research the tumor microenvironment intensively in the lab, and bring the company to important milestones over the next 12 to 24 months with that cash runway.
Excellent. Anything from the audience? On CX-2029, how would you push back on the view that the anemia rates are just too much to overcome for the program to be successful in esophageal?
Yeah. I think that we have to learn more about how to use the drug, as I mentioned. You can see from the comments I made and the data that I showed that, you know, the paradigm that's emerging, and it's still early. I think first and foremost, we have to say this is still a very unique, very novel drug candidate. No one's done something like this before. We'll continue to learn how to best use this drug in the clinic. One example of that is that, as I mentioned, patients who respond tend to respond relatively quickly because it's an ADC. They also. Anemia is highly predictable. Most patients will get anemia at some level, and as we said, about 70% get grade three.
If a patient's responding, the investigator is highly motivated to keep patients on drug. They have three main ways to do that: transfusions, dose reductions, and dose delays. It's a combination of those three mitigation strategies that have been utilized to ensure that these responders have had pretty decent durability. You know, if a patient's not responding to the drug, it's a different equation in terms of thinking about other opportunities for them if they're not responding by the first or second cycle. Again, we'll learn more. We have learned a lot more over the last year. When we look at this signal as an example in squamous esophageal unselected patient population, you're in the fourth or fifth line, a rapidly progressing disease, patients with no other options, I think there's something to follow up on here.
Excellent. Just as a follow-up. Outside of those three, you know, conventional methods of addressing anemia, you had mentioned that, you know, you're considering other methods. What beyond those three methods?
Yeah. We've done some work exploring whether EPO related agents could have some benefit here. I think it's still. It hasn't jumped out at us as a mechanism that's gonna help. We do think that the anemia is resulting from impact on relatively early erythropoiesis. We haven't quite figured out yet the optimal way to use EPO or whether that actually would, in the end, be the right strategy. We continue to look at that. We're working with AbbVie on other potential strategies. We'll have more to say, I would think, as the year progresses.
Excellent. Priyanka.
I have a question regarding the partnerships that are a part of the business model. As you mentioned, you've partnered with Moderna and AbbVie, of course. Has the % range of the tiered royalties been made public by any chance?
Not in specific terms. We've given. I'll give you a couple of examples. In the case of the Moderna alliance, royalty rates that reach into the low to mid-teens. In the case of the AbbVie deal, that's got a bit of a different financial structure, where, as I mentioned, as global development, as and when global development moves forward, we have the opportunity to fund 35% of global development up to pre-negotiated caps. In exchange for that, we receive 35% of U.S. commercial rights and royalties ex-U.S. that actually go into the 20s. You know, each deal is a little bit different. Those are just a couple of examples.
Thank you.
Any final questions?
First question. Do you expect to read out on the CX-904 program this year? Can you comment at all on that?
This is a year of execution in that program for sure. You know, we're really pleased to be through the initial single patient cohorts and into three plus three. As you, I'm sure you know, those escalations for T-cell engagers need to be done thoughtfully, methodically, and we don't currently have any guidance on timing to data.
Thank you.
We actually have one from the portal. Is your masking modality, is that universal, or does each drug require its own specific?
Yeah, great question. A core component of our technology is the masking platform that we use to select peptide masks for antibodies, and that's done on an antibody by antibody basis. We screen highly diverse peptide libraries. Usually, a range of different peptides will come out of that screen, and then we optimize the mask in the context of the protease-cleavable linker, and of course, a lot of in vivo pharmacology to eventually settle on the lead clinical candidate. The masks are different for every program.
Any more questions?
Can I just ask one?
Sure. Yeah.
How do you think about for your holion programs, CX-2051 as well as CX-801? Think about sort of the range of indication selections that you could do for either.
Yeah, there's a lot of potential there. I showed a few tumor types for EpCAM. EpCAM is really, really high in GI tumors, but it's also high in many other tumor types. Ovarian, as an example, lung as an example. I think, you know, we're, we haven't settled on our strategy yet for phase I. I can see, though, an element of it being really pretty focused in certain tumor types where we know expression level is high and we have strong preclinical data to support. I think we'll also cast a fairly wide net as well.
Great. Any final questions? All right. I appreciate it. Thank you, Sean.
Great. Thank you everyone for your time.