CytomX Therapeutics - Q4 2022

Transcript

Operator (participant)

Good day, and thank you for standing by. Welcome to the CytomX Therapeutics fourth quarter 2022 financial results conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker for today, Chris Ogden. Please go ahead.

Chris Ogden (SVP of Finance and Accounting)

Thank you. Good afternoon, thank you for joining us. Before we begin, I'd like to remind everyone that during this call, we'll be making forward-looking statements. Forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our 2022 full year financial results and highlights recent progress at CytomX.

We encourage everyone to read today's press release and the associated materials, which include the 2022 10-K and 2021 amended 10-K, which have been filed today with the SEC. Please also note that comments made in this call regarding the company's financials reflect restated financial statements as outlined in our most recent SEC filings today. The adjusted financial statements reflect changes in the timing of certain revenue recognition in the years from 2019 to 2022. The press release, a recording of this call, and our SEC filings can be found under the investors and news section of our website. With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide a business and pipeline update before I walk through the financials for 2022. Let me turn the call over to Sean.

Sean McCarthy (CEO and Chairman)

Thanks, Chris, good afternoon, everyone. Thanks for joining us for an update on recent progress at CytomX. On today's call, I'll provide an overview of the company's therapeutic pipeline, including status updates for our emerging programs, CX-904, CX-801, and CX-2051. I'll also cover recent developments within our CD71 targeting program and additional updates on our corporate partnerships. At CytomX, we believe that as biologic anti-cancer therapies become more and more potent, the need for localizing empowered modalities such as antibody-drug conjugates, T-cell engagers, and cytokines into cancer tissue becomes increasingly important as a way to improve therapeutic window. We believe that localization will be the future of biologics. CytomX's vision is to transform lives with safer, more effective therapies.

We aim to realize our vision for the benefit of patients by leveraging our Probody platform to create high-impact therapeutics that are localized to disease tissue, thereby reducing systemic toxicities and maximizing overall benefit. 2022 was an important year of transition for our company in which we restructured and repositioned CytomX for future success by prioritizing our earlier stage portfolio that incorporates learning from our experience with the first wave of Probody therapeutics that we pioneered and advanced into the clinic. Since our early years, CytomX has pursued a consistent strategy focused on long-term company build around the Probody platform and maximizing impact for patients. Our substantial investments to date have allowed for broad clinical evaluation of our platform, have resulted in a uniquely strong scientific foundation and a deep pipeline of therapeutic candidates positioned to deliver significant near and long-term value.

We currently have more than 15 active Probody therapeutic programs, including three clinical stage molecules, and we expect to file two new INDs for wholly owned programs later this year. Additionally, through our collaborations, we have substantially extended the reach of our science. CytomX entered 2023 with robust financial resources and funding into 2025, positioning the company to execute towards multiple milestones over the next 12-24 months. Moving now to our pipeline, I'd like to start with T-cell engaging bispecifics and our company's expanding efforts with this modality. T-cell engagers 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, imposing constraints on therapeutic window. Localization of the powerful anti-cancer activity of this class of drugs could unlock enormous potential for patients by enhancing therapeutic window.

CytomX and our partners believe the Probody platform to be ideally suited to addressing this challenge. Our lead program in this area is CX-904, a clinical stage Probody T-cell engager targeting EGFR and CD3, partnered with Amgen in a global co-development alliance. We see a compelling opportunity to leverage this target to localize antitumor T-cell responses preferentially to the tumor microenvironment. Our published preclinical data show 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. We're now well underway with phase I dose escalation. The phase I study has advanced from initial single patient cohorts into the 3+3 phase of dose escalation.

The primary goal of dose escalation for this drug candidate is to assess safety. We aim to reach dose levels and exposures by the end of 2023, at which we can start enrollment into backfill cohorts in certain EGFR-positive tumors. Looking ahead to 2024, a key milestone on the horizon will be the selection of recommended phase II dose and the potential decision to initiate phase Ib expansion cohorts in EGFR-positive tumors. This decision will be taken in conjunction with our partner, Amgen. CytomX would then be responsible for the execution of expansion cohorts. Upon the conclusion of the expansion phase, Amgen will take over global development, with CytomX retaining certain co-funding, co-development, and co-commercialization rights. We look forward to providing additional CX-904 updates as the program advances.

Staying with T-cell engagers, we were delighted that in January 2023, our partner Astellas nominated the first collaboration clinical candidate, triggering a $5 million milestone payment to CytomX. CytomX and Astellas are also collaborating on additional T-cell engagers, and CytomX is eligible to receive future pre-clinical, clinical, and commercial milestones across these programs. We also retain the option to select U.S. development and commercial rights within the Astellas collaboration. Continuing with T-cell bispecifics, in November 2022, CytomX entered a multi-target R&D collaboration with Regeneron to discover and develop new bispecific immunotherapies. Regeneron has considerable efforts in 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 of CytomX scientific and platform expertise. Moving now to our upcoming INDs for next generation molecules, CX-2051 and CX-801. Starting with CX-2051, our conditionally active Probody ADC targeting EpCAM. EpCAM has been regarded as a high potential target for decades and has been clinically validated by others, but clinical activity has only been achieved with local administration. CX-2051 is tailored to optimize therapeutic index for EpCAM-expressing epithelial cancers by matching the target with payload mechanism of action and tumor sensitivity. We have optimized masking, protease cleavability, and we have selected a camptothecin derivative, a topoisomerase I inhibitor in the TCAM class, as the payload for this program, and with a drug-antibody ratio of 8.

The TCAM payload class has shown exciting clinical results with ADCs, including ENHERTU and TRODELVY. We really think this payload is an optimal choice for this program. Although locally administered anti-EpCAM therapeutics have shown promise, efforts to generate systemic anti-EpCAM therapeutics have to date not been successful. CX-2051, however, when systemically administered, has demonstrated a wide predicted therapeutic index and strong preclinical activity in multiple preclinical models, including colorectal cancer. We anticipate filing an IND for this novel ADC in the second half of 2023. Turning now to CX-801, our dually masked interferon alfa-2b, the lead program within our broad efforts in the cytokine field. We believe there's enormous potential to harness the powerful anticancer activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation.

Interferon alfa-2b is an approved immunotherapeutic that has demonstrated clinical activity in multiple cancer types, and we believe provides a potentially superior approach to activating antitumor immune responses than cytokines such as IL-2, IL-12, and IL-15. Interferon alpha stimulates antigen-presenting cells to activate cytotoxic T-cells and combines effectively with checkpoint inhibition, offering tremendous potential to unlock checkpoint refractory and/or resistant cancers. Interferon alpha also has direct tumor cell killing activity, providing a dual mechanism of action. However, the powerful anticancer activity of interferon alpha has thus far been difficult to harness due to its systemic toxicity. In data presented at SITC 2022, we demonstrated that CX-801 has a wide therapeutic index and 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 inhibitors.

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. Let me turn now to our CD71 program. At CytomX, we have had a long-standing interest in leveraging the unique molecular properties of CD71, the transferrin receptor, as an anticancer target. Our goal is to use our Probody platform to open a therapeutic window for this high potential, but previously undruggable target. As such, we have developed an antibody-drug conjugate to CD71 that we call CX-2029. We partnered the program with AbbVie in an alliance that dates back to 2016. That was focused on the advancement of CX-2029 into IND-enabling and clinical studies.

Under the collaboration agreement, CytomX was responsible for early development up to the completion of cohort expansions, with AbbVie being responsible for later-stage development. We've made substantial progress since this alliance started. In January this year, we announced updated results from the cohort expansions, which included encouraging clinical activity in unselected, heavily pretreated patients with tumors of squamous histologies, including a 21% confirmed response rate in squamous esophageal cancer. Grade 3 anemia remains the most common treatment-related adverse event. Strategies for management of anemia have included transfusions, dose delays, and dose reductions. Patients who have responded to CX-2029 have been actively managed through the use of anemia mitigation measures.

Our January data update for CX-2029 essentially marks the conclusion of CytomX's responsibilities for execution of the clinical program within the AbbVie alliance. The data has been under evaluation at AbbVie in recent months. AbbVie informed us on March 21st that they do not plan to advance CX-2029 into further clinical studies for strategic portfolio reasons. The alliance will conclude. CytomX regains full rights to CD71 and has an exclusive option to reacquire full rights to CX-2029. These discussions are underway. While we're disappointed with AbbVie's decision, in our work to date on CD71, we have pushed new scientific boundaries and demonstrated for the first time that targeting CD71 with an antibody-drug conjugate can lead to tumor shrinkage in late-stage cancer patients.

Going forward, CytomX will be evaluating next steps for CX-2029, while also continuing to pursue next-generation strategies to targeting CD71. We would like to thank AbbVie for their partnership in helping us bring CX-2029 and our CD71 program to this stage in its development. I'd like to now briefly update on our collaborative work with Bristol Myers Squibb and Moderna. Our alliance with BMS has continued to make progress, I would like to take a few minutes to cover the latest updates on the CTLA-4 program. We have worked with BMS on two CTLA-4 ProBody approaches. The first is a ProBody version of ipilimumab that's called 249. We're also working with BMS on a ProBody version of their non-fucosylated anti-CTLA-4 antibody, designed to be a more potent version of ipi.

This ProBody, named 288, is designed to be a safer, more effective version of the non-fucosylated ipi. At the earnings call a few weeks ago, BMS announced their prioritization and advancement of the non-fucosylated ProBody 288, which is now the leading edge of their next generation CTLA-4 program. At SITC in 2022, BMS presented phase I data on 218, which is the non-fucosylated antibody that underlies 288, showing intriguing activity, including in microsatellite stable colorectal cancer. The 288 ProBody is being advanced to phase II, and we look forward to future updates from BMS. Lastly, I'd like to reemphasize our most recent collaboration with Moderna, which highlights CytomX's continued innovation, breadth, and pioneering efforts in the field of conditional activation, and also our continued ability to leverage partnering as a financing vehicle for our company.

We're excited to have already kicked off this collaboration, which brings together two leading platforms to research and develop mRNA-encoded, conditionally activated biologics. CytomX and Moderna share a vision of investing at the intersection of biology and technology to transform the lives of patients in oncology and also in non-oncology therapeutic areas. We look forward to doing great things together. Let me now turn the call over to Chris to provide you with a financial overview for the quarter.

Chris Ogden (SVP of Finance and Accounting)

Thank you, Sean. I'm pleased to be able to share an update on our 2022 financial results with you today. CytomX entered 2023 with a strong balance sheet, with $194 million in cash equivalents, and investments as of December 31, 2022, which we project will fund the operations of the company into 2025. This amount includes the upfront payment received as part of the Regeneron collaboration, but does not include the upfront payment of $35 million received in Q1 2023 from Moderna. We continue to operate from a position of financial strength, and our recent collaborations continue to highlight CytomX's ability to leverage its differentiated science to bring capital into the company and build long-term value. Moving to the financials for the full year 2022.

I would like to note that my comments regarding the financial statements refer to our most recent SEC filings, which include restated financial information from 2019 to 2022 as a result of a change in our revenue recognition accounting method for certain collaboration agreements. The restatement impacts the timing of certain revenue recognition and does not impact total revenue that will be recognized for each collaboration. The restatement has no impact on the company's current cash position or cash flows. Revenue in 2022 was $53.2 million compared to $37.3 million in 2021, driven by higher estimated percentages of completion for research and development programs in the company's collaborations with AbbVie and Bristol Myers Squibb. R&D expenses decreased by $2.5 million to $111.6 million in 2022.

The decrease was primarily due to lower clinical trial and lab contract services, partially offset by $5.3 million of restructuring expenses. G&A expenses increased $3.6 million in 2022 to $42.8 million, driven primarily by $2.4 million of restructuring expenses. Overall, full year 2022 expenses related to the company's restructuring, which was announced in July of 2022, were $7.7 million. The restructuring is substantially complete as of the end of 2022. With that, I'll turn the call back to Sean.

Sean McCarthy (CEO and Chairman)

Thanks, Chris. In summary, CytomX has begun 2023 with strong execution across the pipeline and with considerable momentum. This will continue to be a year of focused execution by the company across our partnered and wholly owned pipeline. Our progress with CX-904, taken together with our exciting collaborative efforts with Regeneron and Astellas, positions the company with significant ongoing efforts in T-cell engagers and an opportunity to make an important impact in one of the most promising areas of oncology R&D. We also continue to invest in cancer immunotherapy strategies through our work on CX-801, our conditionally active interferon alpha, which is on track for IND filing this year.

As we assess potential next steps for the CX-2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC, CX-2051, targeting EpCAM towards IND filing. The translational cycle of bench to bedside to bench has continued to teach us where the highest impact applications of our technology lie for the benefit of people with cancer. We remain strongly committed to our patients. I would like to extend my sincere thanks to the CytomX team for their ongoing dedication and commitment to our vision and mission. Operator, let's now open the call up for Q&A.

Operator (participant)

Thank you. As a reminder, if you would like to ask a question, please press star one one on your telephone. One moment while we compile the Q&A roster. The first question we have is coming from Roger Song of Jefferies. Your line is open.

Roger Song (Senior Analyst of Equity Research)

Great. Thank you for taking the question, and thanks for the update. A couple of questions from us, maybe start from the 904. Sean, you mentioned, you potentially will go through the dose escalation by the end of this year and moving into the expansion next year. Can you just give us some kind of comments around what should we expect to see in terms of the data update from that program? What are the key criteria for you to move into the tumor-specific expansion? Thank you.

Sean McCarthy (CEO and Chairman)

Yeah. Hi, Roger. Thanks for the question. As I mentioned, you know, we're pleased with the progress in the early program for CX-904. The goal of the dose escalation that we're engaged in right now is really to assess safety of this very novel T-cell engager. We do believe, you know, we're on track to or our goal is to reach doses by the end of the year that should enable us to start, you know, backfilling cohorts, you know, as is fairly common in early phase I. With an agent like this, really, like any T-cell engager, you know, it's a stepwise dose escalation. These are highly potent molecules.

The selection of doses to move forward, I think these days we need to be even more thoughtful about this given FDA's guidance with Optimus and you know, how to think about MTD, how to think about RP2D. You know, we're gonna be thoughtful here and not ready to guide to when when we'll have data. We are, you know, we are making good progress.

Roger Song (Senior Analyst of Equity Research)

Okay. That's fair. In terms of your upcoming IND for CX-801 and CX-2051, can you just let us know what the status of the IND enabling studies, in terms of the CMC and the tox study you're doing? Also, what are the initial indications for those two, the potential INDs? Thank you.

Sean McCarthy (CEO and Chairman)

Yeah. Thanks for the question. Very excited about these two new INDs. As I've mentioned, they have broad potential across multiple tumor types. As you mentioned, Roger Song, you know, the team is very busy right now with IND-enabling activities for both of these programs. We're, you know, we're pleased with the progress. We're on track with, you know, manufacturing steps with toxicology programs and, you know, everything remains on track for our guidance for these INDs being filed this year. In terms of tumor types, you know, let's take EpCAM first. One of the things we love about this target is just how broadly expressed it is on epithelial tumors.

I did call out CRC in my comments a few moments ago, as, you know, this is the tumor type where EpCAM is the most highly expressed. It's very highly expressed in CRC, and that's one of the reasons that we've selected the camptothecin payload, which we think is well matched to that tumor type, given the high target expression as well. There are many other tumor types that we could potentially move into, including pancreatic, ovarian, to name just two. Many different areas to go. We'll be guided by what we see in phase I, of course. With regards to CX-801, interferon has been approved in several tumor types in the past. We already know it's an active drug, it's an approved drug.

Our strategy there with CX-801, given the potency of interferon alpha as an immunotherapy, is to work in the area of, you know, increasing antitumor immunity, turning colder tumors into warmer tumors, turning warmer tumors into hot tumors. There'll be several opportunities to pursue there. Again, we'll be guided by the phase I dose escalation data, once we get that up and running.

Roger Song (Senior Analyst of Equity Research)

Great. Thanks for the comments. Maybe just one last question, I will hop back on the queue, is for the CD71. Since you are regaining the rights for this target and potentially for the entire 2029. You talk about the next generation for CD71, and we know, the anemia is the on target kind of for Probody finding you have been observing. Can you just let us know what are the key strategies for the next generation and how you're gonna apply from the learning from the previous clinical data to the next generation? Thank you.

Sean McCarthy (CEO and Chairman)

Yeah, thanks. Great question. With regard to, let's maybe start with the 2029 data. You know, just to give, I guess our holistic view of the drug. You know, we have an active drug. This is an ADC, a very novel ADC that has shown antitumor activity in several tumor types, and, you know, most recently this really intriguing signal in squamous esophageal. You know, we've learned more about anemia over the last year or so. We still have more work to do to further understand how to potentially manage and mitigate anemia, you know, if we were to move 2029 forward ourselves, assuming that that was something that we ultimately decide to do.

You know, I think we've learned a lot with CX-2029, over the last couple of years. There is a therapeutic window for the drug. I think it's fair to say that we believe with next gen, we could broaden that therapeutic window. Different ways to do that would be to increase the antitumor activity, find ways to decrease the incidence of anemia. We have several ideas as how to do that. I would anticipate we'll have more to say about this science as we go through, go through the year.

Roger Song (Senior Analyst of Equity Research)

Great. Thanks. That's it for now.

Operator (participant)

Thank you. One moment while we prepare for our next question. Our next question is coming from Mara Goldstein of Mizuho Group. Please go ahead. Your line is open.

Mara Goldstein (Managing Director and Senior Biotechnology Research Analyst)

Great. Thanks for taking the question. Just, maybe to clarify a little bit on CX-2029, you have rights to CD71, but you would then have to acquire the CX-2029 molecule if you chose to do that. Is that correct?

Sean McCarthy (CEO and Chairman)

That's right, Mara. Yes. The target, you know, the program broadly, you know, as far as the target is concerned, reverts to CytomX CX-2029 as a phase II asset. We have an exclusive right to negotiate full rights back from AbbVie and, you know, those discussions have been initiated.

Mara Goldstein (Managing Director and Senior Biotechnology Research Analyst)

Okay. Okay. Fair enough. Then, under the AbbVie, the original AbbVie agreement, they had chosen a second target a couple of years ago. Is that still ongoing or is that also no longer active?

Sean McCarthy (CEO and Chairman)

Yeah. We had two separate collaborations that were initiated at the same time with AbbVie. One was the CD71 R&D agreement, and the other was a research discovery agreement. That's the collaboration under which a couple of additional targets for ADCs.

Mara Goldstein (Managing Director and Senior Biotechnology Research Analyst)

Mm-hmm.

Sean McCarthy (CEO and Chairman)

were selected. That agreement is also coming to a conclusion as well.

Mara Goldstein (Managing Director and Senior Biotechnology Research Analyst)

Okay. fair enough. I wanted to ask on the Moderna collaboration. I certainly understand it's at an early stage, but can you talk to us a little bit about the sort of visibility from, you know, from your perspective in terms of what you may or may not be able to speak to, particularly as it relates to where the benchmarks are for CytomX to A, participate, not just financially, but also potentially clinically?

Sean McCarthy (CEO and Chairman)

Well, just again, to reiterate just how excited we are about the science that we're doing with Moderna that we've just kicked off. So just to recap, you know, the goal of the alliance is to leverage their mRNA platform to encode and express conditionally activated biologics in oncology and non-oncology. You know, we're not ready to disclose additional details of the research program at this point, but the collaboration is structured such that, you know, we are responsible for certain discovery and lead optimization efforts, and Moderna will be responsible for development and commercialization with milestones and royalties coming to CytomX. We do not expect to be involved in the development activities with Moderna.

you know, unlike, for example, the relationships with AbbVie or even Amgen on 904, this is in some ways a more traditional discovery relationship in which Moderna will be conducting the development of the programs as they mature and move forward.

Mara Goldstein (Managing Director and Senior Biotechnology Research Analyst)

Okay. All right. Thanks so much. I appreciate it.

Sean McCarthy (CEO and Chairman)

You're welcome.

Operator (participant)

Thank you. One moment while we prepare for the next question. Our next question will be coming from Peter Lawson of Barclays. Your line is open.

Speaker 8

Hey, good afternoon, guys. Thank you for taking our question. This is actually, this is Alex on for Peter. I just had two quick questions on the BMS collaboration. The first one is, can you comment or remind us the key differences that you saw in phase I for the 218 molecule compared to the data we've seen for the 249 molecule?

Sean McCarthy (CEO and Chairman)

Yeah, happy to comment on that. It does take a bit of time to sort of cover the various moving parts here. Just bear with me for a second, just so we're all on the same page. 249 is the Probody version of Ipi. 218 is the non-fucosylated antibody, which is BMS's antibody. Then there's 288, which is the Probody version of 218, the non-fucosylated. The clinical data that BMS has presented previously relates to, as you rightly point out, to 249's phase I study, and also the 218 phase I study. No data has yet been presented for 288, which is the non-fucosylated Probody.

I would say that the key learnings from the phase I work on CX-249 and BMS-986218 are as follows. With the Probody CX-249, the Probody version of Ipi, the dose escalation was able to achieve really very high levels of the masked Ipi. They achieved 30 mg per kg of monotherapy and 15 mg per kg in combination with full-dose nivo. You can see how, and I think this is pretty consistent with the work we've done over the years in the clinic, that the masking, you know, shifts the dose response curve for toxicity, so they can get to higher levels and still have a well-tolerated drug.

The other aspect of the phase I data, this was really the update last year at ESMO. Clear evidence of clinical activity for CX-249 demonstrated in that poster presentation, including a response in MSS stable CRC, which was highlighted as a case study. The 218 poster was important, I think, for several reasons. Demonstrated again that 218, the non-fucosylated Ipi, is clinically active. Again, a case study was put forward in MSS CRC, which is an area where we're seeing, you know, a lot of progress by others, including Agenus with their Fc-enhanced CTLA-4. The other noteworthy data from the 218 poster is that this drug, you can see how it's a lot more potent.

It's designed to be more potent than Ipi. The non-fucosylation leads to a more potent drug. That meant that the doses administered are substantially lower than for Ipi alone. I think that's kind of an interesting take home. The prioritization of 288, the masked version of that 218, I would think has the potential to evaluate higher doses of the non-fucosylated in masked form. You know, we don't have a lot of visibility at this point in what BMS's phase II strategy will be for 288. Those are just a few thoughts from the data that's been presented thus far.

Speaker 8

Okay, great. Yeah, that makes a lot of sense. Then, yeah, just, I was also curious if you have any visibility in terms of, or should we assume that the current ongoing studies with the CX-249 will sort of stop enrolling patients and, going forward? That's it. Thank you.

Sean McCarthy (CEO and Chairman)

You're welcome.

Operator (participant)

Thank you. One moment while we prepare for the next question. Our next question will be coming from Mitchell Kapoor of H.C. Wainwright. Your line is open.

Mitchell Kapoor (Equity Research Analyst)

Hi, Sean and team. Thanks for taking the questions. hope you're well. Just wanted to ask about CX2029 and, a little bit more on the discussions to re-reacquire the rights. What does that entail? Secondly, what do you think the ability to more effectively treat esophageal cancers versus other cancers suggests about the profile and the mechanism of the drug with respect to the target?

Sean McCarthy (CEO and Chairman)

Yeah. Thanks for the questions, Mitch. Can't really comment on the CX-2029 negotiation for obvious reasons at this point, other than to say that those discussions have been initiated, and there's a process laid out in the contract that we negotiated some years ago for, you know, how to go about that. You know, we'll see where it all goes. With regard to esophageal, it is really interesting to us, the signal that we've seen there. One of the intriguing features of esophageal that relates to the target is, you know, published data from others, showing or suggesting that CD71 is amplified in certain squamous esophageal tumors. You know, one could certainly imagine that there is a relationship between target level or more specifically, target amplification and clinical activity. That is something that we're aggressively pursuing as you know, to figure out whether there's a potential patient selection strategy there.

You know, speaking in, you know, general terms, of course, given the, you know, the high incidence of anemia that we have with this drug, but also given its clinical activity, you know, if we elect to move the drug forward in esophageal, let's say, obviously we'd be wanting to do everything we can to select patients in our favor to increase the likelihood of response and also, of course, continue to work to find ways to manage and mitigate anemia to give the drug, you know, its best chance of future success. That's something that we're actively looking at that relates, you know, directly to the target.

Mitchell Kapoor (Equity Research Analyst)

Okay, great. Thank you very much for taking my questions.

Sean McCarthy (CEO and Chairman)

You're welcome.

Operator (participant)

Thank you. One moment while we prepare for the next question. The next question will be coming from Anupam Rama of JPMorgan. Your line is open.

Malcolm Kuno (Equity Research Associate)

Hi. Thank you for taking the question. This is actually Malcolm Kuno on for Anupam. Just one quick question. Given that some of your collaborations involve cost-sharing agreements, what should we assume as being baked into your cash runway?

Sean McCarthy (CEO and Chairman)

I'll pass that one over to Chris.

Chris Ogden (SVP of Finance and Accounting)

Hi, Malcolm. Just to reiterate what we've communicated on cash runway in the prepared remarks. So we reported $194 million of cash at the end of the year. As I mentioned, that does not include the Moderna upfront payment of $35 million received in Q1 of 2023, nor the Astellas milestone that we achieved of $5 million in January of this year. In terms of, you know, color on the guidance, we don't, you know, go into specifics on exactly what's assumed. You know, from an overall capital allocation and resourcing perspective, you know, we communicated in the summer of last year, you know, the focus on CX-904 and the, you know, next generation pipeline. Of course, capital will be allocated to those programs as appropriate, but beyond that, we're not giving additional color.

Malcolm Kuno (Equity Research Associate)

Okay. Thank you.

Sean McCarthy (CEO and Chairman)

Yeah. I would just add just one quick addition that there in terms of the, you know, the deal structures, again, as we mentioned in the comments earlier, both the AbbVie and Amgen alliances have been structured in a way that, you know, with AbbVie we had, I guess now we're obviously concluding that relationship, but we had and with Amgen we have the opportunity to invest in later stage development, you know, but that's quite a bit further down the road. As Chris mentioned, you know, our current financials and guidance is really focused on advancing the earlier stage programs to key near-term milestones.

Malcolm Kuno (Equity Research Associate)

That makes sense. Thank you.

Operator (participant)

Thank you. One moment while we prepare for the next question. The next question is coming from Etzer Darout of BMO. Your line is open.

Etzer Darout (Managing Director and Senior Biotech Analyst)

Great. Thanks for taking the question. Just wanted a clarifying question on the Probody program from BMS. Just sort of namely whether or not 249 is ongoing and advancing. Is this just sort of a leapfrog of 288, or is that the only program that BMS plans to move forward? I guess that's question one. If you could maybe speak to sort of maybe the safety tolerability differences potentially between 218, the antibody from Bristol and the, you know, IP sort of AE profile which, you know, we now know are fairly notorious. If you could maybe talk a little bit about that as well. Thank you.

Sean McCarthy (CEO and Chairman)

Yeah. Thanks, Etzer. Obviously, questions will, you know, I think be probably more, more comprehensively answered by our, by our partner, BMS. Let me just make a couple brief comments. First of all, with regard to the 288 leapfrog, as you put it, you know, they have been pretty clear that they have prioritized 288 over the other programs. The advancement from phase I to phase II reflects that. I think if one looks at the broad landscape of CTLA-4 next gens that are being pursued by various parties, yeah, there is a move towards more potent versions of anti-CTLA-4 antibodies using strategies like Fc enhancement, or in the case of BMS, you know, non-fucosylation which are, you know, functionally, you know, very, very similar.

Their decision, I think looking at it from the standpoint of the outside world and the way the field's evolving, makes sense to us. With regard to safety of 218, again, I think the question would be much better answered by our partner. I would just observe from the data that we've seen in their presentations that 218, as I mentioned earlier, is a more potent antibody when one thinks about engagement of the target biology. It is, it's less well-tolerated. I think the profile though, of adverse events that are seen, are similar. I'm not aware of anything that's particularly unique with the Fc-enhanced, but would have to study the data a bit more closely.

Etzer Darout (Managing Director and Senior Biotech Analyst)

Got it. Thank you for the update.

Sean McCarthy (CEO and Chairman)

The goal of the. Yeah. The goal of the Probody, of course, is to, you know, open that therapeutic window, and that's why we're encouraged that they prioritize 288.

Etzer Darout (Managing Director and Senior Biotech Analyst)

Got it. Yep. Thank you.

Sean McCarthy (CEO and Chairman)

You're welcome.

Operator (participant)

Thank you. That concludes today's Q&A session as well as concludes today's conference call. Thank you all for joining. You may disconnect, and have a good evening.