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spk02: Good day, and thank you for standing by. Welcome to the Cytomics Therapeutics Fourth Quarter 2023 Financial Results Conference Call. At this time, all participants are on 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 Starboy 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, Please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, Chris Ogden, Senior Vice President, Finance and Accounting. Please go ahead.
spk09: Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements. Because 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 2023 full-year financial results and highlights recent progress at Cytomix. We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, 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, Cytomix's Chief Executive Officer and Chairman. Sean will provide introductory comments on Cytomix's progress and key milestones before we cover our pipeline progress and financials for the fourth quarter and expectations for the year ahead. With that, I'll now turn the call over to Sean.
spk03: Thank you, Chris, and good afternoon, everyone. Thanks for joining us for an update on Cytomix's continued progress. The promise of masking and conditional activation strategies to improve the therapeutic window for potent biologics like ADCs, T-cell engagers, and cytokines continues to be an important and exciting frontier in cancer R&D. And our leadership in this field at Cytomix derives from more than a decade of innovation with the ProBody therapeutic platform. Our foundational clinical work with the ProBody platform has achieved many firsts in demonstrating how masking strategies can be effective in cancer patients, and we have opened a broad field in which progress continues to accelerate. The Cytomix team is highly focused on delivering on the promise of conditional activation for the benefit of patients. We're currently advancing a generation of product candidates that span multiple modalities, leveraging validated oncology targets, potent effective mechanisms, and tailored masking strategies. Each of our candidates is designed to address large commercial markets and major unmet medical need in cancer. We've had a highly productive start to 2024. We remain on track for initial CX904 Phase Ia dose escalation data in the second half of this year. And we're busy launching Phase I clinical trials for our newest therapeutic candidates CX2051, and CX801, with initial Phase Ia data anticipated in 2025. Let me now provide additional context and detail for our lead programs. I'll start with our, with CX904, our pro-body T-cell engager targeting EGFR and CD3. T-cell engaging bispecific antibodies have enormous potential for the treatment of cancer. and first demonstrated meaningful clinical benefit in hematologic malignancies. Looking across the T-cell engager landscape for solid tumors, it's taken time to see meaningful clinical results, but we're now starting to see important breakthroughs generating great excitement. Successes include Immunocorps tibentifus in uveal melanoma, the first approved T-cell engager for solid tumors, And more recently, Amgen's Tarlatamab targeting DLL3, which has demonstrated impressive results in small cell lung cancer. The development of these and other programs has not only provided long-awaited proof of concept, but this important work has also helped to increasingly define a roadmap and key considerations for how to optimally develop this emerging class of potent therapies, including optimization of dosing paradigms. However, for this modality to fully break through in solid tumors, there are still significant challenges to overcome. T-cell engagers bring very high potency, and this potency can lead to toxicities in normal tissues, where the tumor adjutant of interest may also be present. In fact, this is very often the case. A normal tissue target expression is widely acknowledged to be a limitation on the development of T-cell engagers for solid tumors. Furthermore, another well-acknowledged limitation for T-cell engagers is cytokine release syndrome, resulting from systemic binding to CD3 on T-cells. At Cytomics, we have a broad-based program focused on masking T-cell engagers to decrease tumor antigen binding in normal tissues and CD3 binding in the periphery, thereby improving therapeutic index. We're working with partners, Amgen, Astellas, Regeneron, and Bristol-Myers Squibb in this exciting space. Our lead program is CX904 that targets the tumor antigen EGFR and CD3 on T cells. CX904 is designed to address the principal challenges of developing an EGFR CD3 T cell engager with the goal of delivering antitumor activity at tolerable systemic doses. This program is partnered with Amgen and a global co-development collaboration. The market opportunity for CX904 is broad. There are hundreds of thousands of EGFR-positive patients with metastatic tumors across a wide range of cancer types that could potentially be addressed by this therapy. Cytomics is currently conducting an ongoing Phase Ia study in late-stage unselected patients with advanced solid tumors generally known to have EGFR expressions. Our principal goal for this Phase 1A study is to evaluate safety and to identify doses and schedules for detailed evaluation in specific EGFR-positive cancer types in Phase 1B. More specifically on safety, we're looking to keep CRS and the typical EGFR-mediated toxicities at manageable levels in order to achieve doses in the predicted therapeutically active range. The selection of phase 1B tumor types will be driven by a combination of factors, including observations from phase 1A, unmet medical need, and commercial potential, including fit with our partner's strategic interests. We're making steady progress in the clinic, having now advanced through multiple dose cohorts and above dose levels that would be expected to be tolerated with an unmasked EGFR T-cell engager. In late 2023, we also began to backfill certain dose levels to more fully explore the profile of this drug candidate. We expect to share initial Phase 1A dose escalation data in the second half of 2024 with our partner Amgen, and also to present these data in an appropriate setting externally. These data will inform a potential decision to initiate Phase 1B in 2025. Moving now to our continued work in the antibody drug conjugate space. There's been tremendous progress in ADCs in the past few years, and the impact for patients has driven significant strategic interest in this field. CX2051 is our first-in-class EPCAM-directed pro-body ADC. Our IND application for CX2051 was cleared by the FDA in January. Clinical study startup activities are in progress, and we expect to initiate phase one dose escalation in solid tumors generally known to have EPCAM expression including colorectal cancer, in the near term. EPCAM is a high potential oncology target due to its high cell surface expression in many cancer types. Indeed, EPCAM was one of the first tumor actions to be characterized more than three decades ago, and it has since been implicated in many roles in cancer progression. Anti-EPCAM therapeutic strategies have shown potent anti-cancer activity in preclinical models, and this has been translated into clinical activity, but to date, clinical success has been limited to local administration because EPCAM is present in so many normal epithelial tissues. Efforts to generate systemically administered anti-EPCAM therapeutics have not been successful to date due to toxicities in epithelial tissues, including the GI tract. Our innovative drug candidate, CX2051, is tailored to optimize the therapeutic index for EPCAM-expressing epithelial cancers by masking the antibody to reduce binding in normal tissues, but to allow activation in tumor tissue. We have armed the antibody with a cytotoxic payload based on capsaicin, a topoisomerase I inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets, leading to dramatic advances for patients. CX2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer. Like EGFR discussed previously, CX2051 could also potentially address a large patient population, as that CAM is highly expressed across many indications, including colorectal, gastric, endometrial, and ovarian cancers. Our phase one trial will follow an adaptive design, and it's intended to demonstrate rapid clinical proof of concepts to inform a potential decision to move into dose expansion studies in 2025. We're really excited to see what this unique and first-in-class ADC can do for patients. Turning now to CX801, our dually masked, conditionally activated interferon alpha 2B which we believe has the potential to become a cornerstone of combination immunotherapy for a wide range of tumor types. The IND for CX801 was cleared by the FDA in January, and we expect to initiate phase one dose escalation in solid tumors, including melanoma, renal cancer, and head and neck squamous cell carcinoma in the first half of 2024. Interferon Alpha is a powerful cytokine with the ability to potently drive tumor antigen presentation and activate anti-tumor immunity. It has demonstrated clinical activity and gained regulatory approval many years ago in multiple cancer types, including melanoma, renal cancer, and bladder cancer. However, interferon therapy is well known to be associated with significant systemic side effects, and its use has been superseded by checkpoint inhibitors and other therapeutic approaches. It's also been shown that interferon can potentiate the clinical effects of PD-1 in metastatic melanoma, but again, this approach has been limited by systemic toxicities. Interferon therapy has recently returned to focus with Ferring Pharmaceuticals' approval in 2022 of adstiladrine, an interferon alpha-2B encoding gene therapy indicated for the treatment of localized BCG non-responsive non-muscle invasive bladder cancer. reaffirming that this potent cytokine could indeed achieve robust anti-tumor responses in patients. Based on the preclinical profile of CX801, as well as prior clinical experience with interferon therapies, we see 801 as a potential new centerpiece of combination cancer immunotherapy. Our preclinical data, most recently presented at 602023, demonstrates synergy for our mass interferon alpha with PD-1 inhibition, both in terms of anti-tumor activity and in activation of the tumor inflammatory microenvironment. Moreover, we've also shown that systemic activity of unmasked interferon is significantly reduced and overall tolerability is markedly improved compared to the unmasked cytokine in animal models. We anticipate The opportunity for CX801 will be in combination with checkpoint inhibition where it could serve as a potent immune modulator to both increase the frequency and durability of responses in IO-sensitive tumors and potentially to establish or restore efficacy in IO-resistant or cold tumors. Our phase one dose escalation trial being initiated in the first half of 2024 will utilize an adaptive design to evaluate safety and signs of clinical activity for 801 monotherapy and advance rapidly to combination with checkpoint inhibition. Before moving to financials, I'd like to provide updates on our partnerships and starting with an update on our longstanding collaboration with Bristol Myers Squibb. We were informed on March 6th of BMS intention to discontinue BMS 986288, the CTLA-4 program. This unexpected decision followed a broad internal portfolio review at BMS. We continue to work with BMS to gain more visibility on the data from this program and the factors that led to this decision. Moving forward, the BMS collaboration continues to be very active and will now focus primarily in the field of T-cell engagers, where together we have initiated several new programs over the last two years. Notably, this shift in focus within the BMS alliance now means that the majority of our partner programs are now focused on T-cell engagers, reflecting strong strategic interest in this area and showing that this modality is emerging as a key application of masking and conditional activations. Continuing the T-cell engager theme, given our ongoing progress with enrollment of the CX904 Phase 1A study, I'd like to outline some of the key terms of our strategic alliance with Amgen. Under the terms of our agreement, Cytomix and Amgen are co-developing CX904. Cytomix is responsible for early stage development, and Amgen will be responsible for late stage development with the transition occurring after completion of Phase 1B by Cytomix. Within the CX904 agreement, Citermix has an option to participate financially in the global co-development of CX904 with Amgen. If we exercise our co-development option, we opt into a significant U.S. profit share, and we are eligible for up to $460 million in development, regulatory, and commercial milestone payments, and ex-U.S. royalties in the low double-digit to mid-teen percentage. We see this collaboration as having substantial potential to build long-term value for Cytomix, and we look forward to making additional progress with our partner on this program. Moving now to our other drug discovery stage partnerships, we continue to make progress in our alliances, including with our newest partners, Regeneron and Moderna. Across our alliances, we have more than a dozen active discovery programs. Cytomix holds significant commercial rights on a number of these assets, And we have multiple near and long-term milestones that we're working towards. Chris will review in a few moments the financial benefits that continue to accrue to us from our partnerships as we run the company in a very capital-efficient way. With that, I'll hand over to Chris to provide a financial update.
spk09: Thank you, Sean. I'm pleased to be able to share an update on our 2023 financial results with everyone today. Cytonics entered 2024 with a strong balance sheet. with $175 million in cash, cash equivalents, and investments as of December 31st, 2023, compared to $194 million at the end of 2022. We expect our cash balance will fund the operations of the company well into the second half of 2025. This cash guidance does not assume any additional milestones from existing collaborations or any new business development. both of which Cytomix has a strong track record of obtaining. Our cash position reflects our focus on controlling costs and efficient capital allocation, as well as our consistent track record of funding the company through a mix of both strategic business development and equity financing over time. Our partnerships have consistently been a strategic pathway for value creation and financing opportunities that allow us to generate non-dilutive capital while increasing the reach of our platform. Our partnerships continue to advance and have generated more than $500 million of incoming cash to date, and we see near-term opportunities for additional milestone payments in 2024 and 2025. Despite a challenging macro environment in 2023, we maintained a strong balance sheet position and executed efficiently to position the company to create potentially significant value inflections that will be realized over the next 12 to 18 months. Now, moving to revenue and operating expenses for the year. Total revenue was 101.2 million for 2023, compared to 53.2 million for the corresponding period in 2022. We saw an increase in revenue due to a higher percentage of completion for research programs in the Bristol-Myers Squibb collaboration and the recent collaborations with Regeneron and Moderna. Operating expense for Q4 2023 was $27.2 million compared to $29.6 million in the fourth quarter of 2022. R&D expenses decreased by $34.3 million from last year to $77.3 million compared to $111.6 million in 2022. General administrative expenses decreased by $13.1 million for the year ended December 31, 2023, to $29.8 million, compared to $42.8 million for the corresponding period in 2022. Overall, our prudent financial management of the company and focused capital allocation priorities has resulted in continued balance sheet strength as we progressed our pipeline. Now, I'll hand the call back to Sean for closing remarks.
spk03: Thank you, Chris, and thanks, everyone, for your time this afternoon and for your interest in cytomics. 2024 promises to be an exciting year for us, and the longer-term outlook for 2025 and beyond is also very compelling as we make progress across our multimodality pipeline. The field of antibody masking and conditional activation is continuing to accelerate, and we remain very well positioned to build on the depth of our experience as a leading innovator in this area. We're leveraging our multimodality probody therapeutic platform to discover and develop new cancer therapies based on T-cell engagers, ADCs, and cytokines, each of which represents a highly relevant and timely area of strategic interest across the industry. The Cytomix team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer. And I'd like to close by thanking everyone involved for their commitment to our vision. With that, Operator, let's go ahead and we can open up the call for Q&A.
spk02: Thank you. As a reminder, if you would like to ask a question, please press star one one on your telephone. We also ask that you wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. Our first question today will be coming from Peter Lawson of Barclays. Your line is open.
spk10: Peter Lawson of Barclays, your line is open. One moment.
spk09: Operator, maybe we could put Peter back in the queue and go to the next question.
spk02: Yes. Thank you. Our next question will be coming from Joe of Piper . Your line is open.
spk07: Hey, everybody. Hopefully, you can hear me okay. Thanks for taking the questions and the update here. So, I know we saw recent data from a competitive masking program, and they showed it looked like near zero detectable unmasked antibody in circulation. Just maybe, can you remind us what you've historically seen with probody programs around this metric, whether you're tracking it for 904 and what your expectations would be? Maybe my follow-up question is on the safety side. So in preclinical TOCS work for 904, I know you've reported some data around CRS, but in GLP work, was it CD3-mediated TOCS or EGFR-mediated TOCS that showed up first and which was dose-limiting? Thanks.
spk03: Yeah, hey, Joe. Thanks for the questions. Yeah, so we're tracking, obviously, all innovations in the field and all progress. I think we can conclude from multiple recent data sets from several companies that, first of all, something that I think we've shown quite some time ago is that masking works. Masking antibodies and other modalities is clearly showing the ability to decrease systemic target engagement and depending upon target and format to also improve tolerability. So we're excited to see this progress across the field. What we've shown over the years pretty consistently with multiple programs, whether it was our PD-L1 probody or 2009, 2009, some of our earlier programs from which we've learned so much, You know, we've shown that the vast majority of the circulating entity, the probody therapeutic, is in masked form. And that, again, has translated into what we interpret as a successful decreasing of target engagement. So, yeah, the field's come a long way. And we're excited to see now in the hands of others these types of approaches also beginning to gain some traction. In terms of our work on EGFR-CD3 and 904, we have presented, I mean, quite honestly, we haven't presented a lot of data on this program for very competitive reasons, but we did share an earlier iteration of our EGFR-CD3 program with pretty extensive characterization in syngeneic animal models and in And, you know, we focused in large part on the cytokine induction in those monkey studies showing a dramatic shift with the masking, you know, dramatic shift in terms of the ability to induce cytokines. But we haven't shared a whole lot of data on the actual CX904 molecule yet. That will come in the future.
spk08: Okay. Thanks. That's helpful. Thanks for taking my question. You're very welcome.
spk02: Thank you. One moment for the next question. Our next question will be coming from Anupam Rama of J.P. Morgan. Your line is open.
spk04: Hi. Thank you so much for taking the question. This is actually Malcolm Kuno for Autopom. So what is the size and scope of the Phase I dose escalation data that we should be thinking about in 2H24 for CX904. And on that, when should we get a better sense of a more granular timeline? Thank you.
spk03: Yeah, thanks for the question. So we remain on track with 904 to share data in the second half as I mentioned in my prepared remarks our principal objective at this moment in time is to build the data set to share with our partner Amgen in the second half of the year and then that would result in presentation externally in an appropriate setting we're not guiding to any specifics at this point in time obviously what we're looking for though in phase 1a is to demonstrate and really fully explore the safety profile of 904 in terms of CRS, in terms of EGFR-mediated toxicities. Obviously, look for any early evidence of anti-tumor activity. And I would expect the update in the second half, you know, it would be a meaningful number of patients, but that's really all that we're ready to say at this moment in time.
spk01: Great. Thank you.
spk02: Thank you. At this time, if you would like to ask a question, please press star 1-1 on your telephone.
spk10: There are no more questions in the queue. Thank you so much for joining the conference call today. Everyone may disconnect. Goodbye. Thank you. Music. Thank you. Thank you. Thank you.
spk02: Good day, and thank you for standing by. Welcome to the Cytomics Therapeutics Fourth Quarter 2023 Financial Results Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you will need to press Starboy One on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, Chris Ogden, Senior Vice President, Finance and Accounting. Please go ahead.
spk09: Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements. Because 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 2023 full-year financial results and highlights recent progress at Cytomix. We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, 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, Cytomix's Chief Executive Officer and Chairman. Sean will provide introductory comments on Cytomix's progress and key milestones before we cover our pipeline progress and financials for the fourth quarter and expectations for the year ahead. With that, I'll now turn the call over to Sean.
spk03: Thank you, Chris, and good afternoon, everyone. Thanks for joining us for an update on Cytomix's continued progress. The promise of masking and conditional activation strategies to improve the therapeutic window for potent biologics like ADCs, T-cell engagers, and cytokines continues to be an important and exciting frontier in cancer R&D. And our leadership in this field at Cytomix derives from more than a decade of innovation with the ProBody therapeutic platform. Our foundational clinical work with the ProBody platform has achieved many firsts in demonstrating how masking strategies can be effective in cancer patients, and we have opened a broad field in which progress continues to accelerate. The Cytomix team is highly focused on delivering on the promise of conditional activation for the benefit of patients. We're currently advancing a generation of product candidates that span multiple modalities, leveraging validated oncology targets, potent effective mechanisms, and tailored masking strategies. Each of our candidates is designed to address large commercial markets and major unmet medical need in cancer. We've had a highly productive start to 2024. We remain on track for initial CX904 Phase Ia dose escalation data in the second half of this year, and we're busy launching Phase I clinical trials for our newest therapeutic candidates CX2051, and CX801 with initial Phase Ia data anticipated in 2025. Let me now provide additional context and detail for our lead programs. I'll start with our, with CX904, our pro-body T-cell engager targeting EGFR and CD3. T-cell engaging bispecific antibodies have enormous potential for the treatment of cancer. and first demonstrated meaningful clinical benefit in hematologic malignancies. Looking across the T-cell engager landscape for solid tumors, it's taken time to see meaningful clinical results, but we're now starting to see important breakthroughs generating great excitement. Successes include Immunocore's tibentafus in uveal melanoma, the first approved T-cell engager for solid tumors, and more recently, Amgen's Tarlatamab, targeting DLL3, which has demonstrated impressive results in small cell lung cancer. The development of these and other programs has not only provided long-awaited proof of concept, but this important work has also helped to increasingly define a roadmap and key considerations for how to optimally develop this emerging class of potent therapies, including optimization of dosing paradigms. However, for this modality to fully break through in solid tumors, there are still significant challenges to overcome. T-cell engagers bring very high potency, and this potency can lead to toxicities in normal tissues, where the tumor antigen of interest may also be present. In fact, this is very often the case. A normal tissue target expression is widely acknowledged to be a limitation on the development of T-cell engagers for solid tumors. Furthermore, another well-acknowledged limitation for T-cell engagers is cytokine release syndrome, resulting from systemic binding to CD3 on T-cells. At Cytomics, we have a broad-based program focused on masking T-cell engagers to decrease tumor antigen binding in normal tissues and CD3 binding in the periphery, thereby improving therapeutic index. We're working with partners, Amgen, Astellas, Regeneron, and Bristol-Myers Squibb in this exciting space. Our lead program is CX904 that targets the tumor antigen EGFR and CD3 on T cells. CX904 is designed to address the principal challenges of developing an EGFR CD3 T cell engager with the goal of delivering antitumor activity at tolerable systemic doses. This program is partnered with Amgen and a global co-development collaboration. The market opportunity for CX904 is broad. There are hundreds of thousands of EGFR-positive patients with metastatic tumors across a wide range of cancer types that could potentially be addressed by this therapy. Cytomics is currently conducting an ongoing Phase Ia study in late-stage unselected patients with advanced solid tumors generally known to have EGFR expressions. Our principal goal for this Phase 1A study is to evaluate safety and to identify doses and schedules for detailed evaluation in specific EGFR-positive cancer types in Phase 1B. More specifically on safety, we're looking to keep CRS and the typical EGFR-mediated toxicities at manageable levels in order to achieve doses in the predicted therapeutically active range. The selection of phase 1B tumor types will be driven by a combination of factors, including observations from phase 1A, unmet medical need, and commercial potential, including fit with our partner's strategic interests. We're making steady progress in the clinic, having now advanced through multiple dose cohorts and above dose levels that would be expected to be tolerated with an unmasked EGFR T-cell engager. In late 2023, we also began to backfill certain dose levels to more fully explore the profile of this drug candidate. We expect to share initial Phase 1A dose escalation data in the second half of 2024 with our partner Amgen, and also to present these data in an appropriate setting externally. These data will inform a potential decision to initiate Phase 1B in 2025. Moving now to our continued work in the antibody drug conjugate space. There's been tremendous progress in ADCs in the past few years, and the impact for patients has driven significant strategic interest in this field. CX2051 is our first-in-class EPCAM-directed pro-body ADC. Our IND application for CX2051 was cleared by the FDA in January. Clinical study startup activities are in progress, and we expect to initiate Phase I dose escalation in solid tumors generally known to have EPCAM expression including colorectal cancer, in the near term. EPCAM is a high potential oncology target due to its high cell surface expression in many cancer types. Indeed, EPCAM was one of the first tumor actions to be characterized more than three decades ago, and it has since been implicated in many roles in cancer progression. Anti-EPCAM therapeutic strategies have shown potent anti-cancer activity in preclinical models, and this has been translated into clinical activity, but to date, clinical success has been limited to local administration because EPCAM is present in so many normal epithelial tissues. Efforts to generate systemically administered anti-EPCAM therapeutics have not been successful to date due to toxicities in epithelial tissues, including the GI tract. Our innovative drug candidate, CX2051, is tailored to optimize the therapeutic index for EPCAM expressing epithelial cancers by masking the antibody to reduce binding in normal tissues, but to allow activation in tumor tissue. We have armed the antibody with a cytotoxic payload based on Captathicin, a topisomerase I inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets, leading to dramatic advances for patients. CX2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer. Like EGFR discussed previously, CX2051 could also potentially address a large patient population as that CAM is highly expressed across many indications, including colorectal, gastric, endometrial, and ovarian cancers. Our phase one trial will follow an adaptive design, and it's intended to demonstrate rapid clinical proof of concepts to inform a potential decision to move into dose expansion studies in 2025. We're really excited to see what this unique and first-in-class ADC can do for patients. Turning now to CX801, our dually masked, conditionally activated interferon alpha 2B, which we believe has the potential to become a cornerstone of combination immunotherapy for a wide range of tumor types. The IND for CX801 was cleared by the FDA in January, and we expect to initiate phase one dose escalation in solid tumors, including melanoma, renal cancer, and head and neck squamous cell carcinoma in the first half of 2024. Interferon Alpha is a powerful cytokine with the ability to potently drive tumor antigen presentation and activate anti-tumor immunity. It has demonstrated clinical activity and gained regulatory approval many years ago in multiple cancer types, including melanoma, renal cancer, and bladder cancer. However, interferon therapy is well known to be associated with significant systemic side effects, and its use has been superseded by checkpoint inhibitors and other therapeutic approaches. It's also been shown that interferon can potentiate the clinical effects of PD-1 in metastatic melanoma, but again, this approach has been limited by systemic toxicities. Interferon therapy has recently returned to focus with Ferring Pharmaceuticals' approval in 2022 of adstiladrine, an interferon alpha-2B encoding gene therapy indicated for the treatment of localized BCG non-responsive non-muscle invasive bladder cancer. reaffirming that this potent cytokine could indeed achieve robust anti-tumor responses in patients. Based on the preclinical profile of CX801, as well as prior clinical experience with interferon therapies, we see 801 as a potential new centerpiece of combination cancer immunotherapy. Our preclinical data, most recently presented at 602023, demonstrates synergy for our mass interferon alpha with PD-1 inhibition, both in terms of anti-tumor activity and in activation of the tumor inflammatory microenvironment. Moreover, we've also shown that systemic activity of unmasked interferon is significantly reduced, and overall tolerability is markedly improved compared to the unmasked cytokine in animal models. We anticipate The opportunity for CX801 will be in combination with checkpoint inhibition, where it could serve as a potent immune modulator to both increase the frequency and durability of responses in IO-sensitive tumors, and potentially to establish or restore efficacy in IO-resistant or cold tumors. Our Phase I dose escalation trial, being initiated in the first half of 2024, will utilize an adaptive design to evaluate safety and signs of clinical activity for 801 monotherapy and advance rapidly to combination with checkpoint inhibition. Before moving to financials, I'd like to provide updates on our partnerships, and starting with an update on our longstanding collaboration with Bristol Myers Squibb. We were informed on March 6th of BMS's intention to discontinue BMS 986288, the CTLA-4 program. This unexpected decision followed a broad internal portfolio review at BMS. We continue to work with BMS to gain more visibility on the data from this program and the factors that led to this decision. Moving forward, the BMS collaboration continues to be very active and will now focus primarily in the field of T-cell engagers, where together we've initiated several new programs over the last two years. Notably, this shift in focus within the BMS alliance now means that the majority of our partner programs are now focused on T-cell engagers, reflecting strong strategic interest in this area and showing that this modality is emerging as a key application of masking and conditional activations. Continuing the T-cell engager theme, given our ongoing progress with enrollment of the CX904 Phase 1A study, I'd like to outline some of the key terms of our strategic alliance with Amgen. Under the terms of our agreement, Cytomix and Amgen are co-developing CX904. Cytomix is responsible for early stage development, and Amgen will be responsible for late stage development with the transition occurring after completion of Phase 1B by Cytomix. Within the CX904 agreement, Citermix has an option to participate financially in the global co-development of CX904 with Amgen. If we exercise our co-development option, we opt into a significant U.S. profit share, and we are eligible for up to $460 million in development, regulatory, and commercial milestone payments, and ex-U.S. royalties in the low double-digit to mid-teen percentage. We see this collaboration as having substantial potential to build long-term value for Cytomix, and we look forward to making additional progress with our partner on this program. Moving now to our other drug discovery stage partnerships, we continue to make progress in our alliances, including with our newest partners, Regeneron and Moderna. Across our alliances, we have more than a dozen active discovery programs. Cytomix holds significant commercial rights on a number of these assets, And we have multiple near and long-term milestones that we're working towards. Chris will review in a few moments the financial benefits that continue to accrue to us from our partnerships as we run the company in a very capital-efficient way. With that, I'll hand over to Chris to provide a financial update.
spk09: Thank you, Sean. I'm pleased to be able to share an update on our 2023 financial results with everyone today. Citonics entered 2024 with a strong balance sheet. with $175 million in cash, cash equivalents, and investments as of December 31st, 2023, compared to $194 million at the end of 2022. We expect our cash balance will fund the operations of the company well into the second half of 2025. This cash guidance does not assume any additional milestones from existing collaborations or any new business development. both of which Cytomix has a strong track record of obtaining. Our cash position reflects our focus on controlling costs and efficient capital allocation, as well as our consistent track record of funding the company through a mix of both strategic business development and equity financing over time. Our partnerships have consistently been a strategic pathway for value creation and financing opportunities that allow us to generate non-dilutive capital while increasing the reach of our platform. Our partnerships continue to advance and have generated more than $500 million of incoming cash to date, and we see near-term opportunities for additional milestone payments in 2024 and 2025. Despite a challenging macro environment in 2023, we maintained a strong balance sheet position and executed efficiently to position the company to create potentially significant value inflections that will be realized over the next 12 to 18 months. Now, moving to revenue and operating expenses for the year. Total revenue was 101.2 million for 2023 compared to 53.2 million for the corresponding period in 2022. We saw an increase in revenue due to a higher percentage of completion for research programs in the Bristol-Myers Squibb Collaboration and the recent collaborations with Regeneron and Moderna. Operating expense for Q4 2023 was $27.2 million compared to $29.6 million in the fourth quarter of 2022. R&D expenses decreased by $34.3 million from last year to $77.3 million compared to $111.6 million in 2022. General administrative expenses decreased by $13.1 million for the year ended December 31, 2023, to $29.8 million, compared to $42.8 million for the corresponding period in 2022. Overall, our prudent financial management of the company and focused capital allocation priorities has resulted in continued balance sheet strength as we progressed our pipelines. Now, I'll hand the call back to Sean for closing remarks.
spk03: Thank you, Chris, and thanks, everyone, for your time this afternoon and for your interest in cytomics. 2024 promises to be an exciting year for us, and the longer-term outlook for 2025 and beyond is also very compelling as we make progress across our multimodality pipeline. The field of antibody masking and conditional activation is continuing to accelerate, and we remain very well positioned to build on the depth of our experience as a leading innovator in this area. We're leveraging our multimodality pro-body therapeutic platform to discover and develop new cancer therapies based on T-cell engagers, ADCs, and cytokines, each of which represents a highly relevant and timely area of strategic interest across the industry. The Cytomix team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer. And I'd like to close by thanking everyone involved for their commitment to our vision. With that, Operator, let's go ahead and we can open up the call for Q&A.
spk02: Thank you. As a reminder, if you would like to ask a question, please press star one one on your telephone. We also ask that you wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. Our first question today will be coming from Peter Lawson of Barclays. Your line is open.
spk10: Peter Lawson of Barclays, your line is open. One moment.
spk09: Operator, maybe we could put Peter back in the queue and go to the next question.
spk10: Yes, thank you.
spk02: Our next question will be coming from Joe Catarzo of Piper Stanley. Your line is open.
spk07: Hey everybody, hopefully you can hear me okay. Thanks for taking the questions and the update here. So I know we saw recent data from a competitive masking program and they showed, looked like near zero detectable unmasked antibody in circulation. Just maybe can you remind us what you've historically seen with probody programs around this metric, whether you're tracking it for 904 and what your expectations would be and then Maybe my follow-up question is on the safety side. So in preclinical TOCS work for 904, I know you've reported some data around CRS, but in GLP work, was it CD3-mediated TOCS or EGFR-mediated TOCS that showed up first and which was dose-limiting? Thanks.
spk03: Yeah, hey, Joe. Thanks for the questions. Yeah, so we're tracking, obviously, all innovations in the field and all progress. I think we can conclude from multiple recent data sets from several companies that, first of all, something that I think we've shown quite some time ago is that masking works. Masking antibodies and other modalities is clearly showing the ability to decrease systemic target engagement and depending upon target and format to also improve tolerability. So we're excited to see this progress across the field. What we've shown over the years pretty consistently with multiple programs, whether it was our PD-L1 probody or 2009, 2009, some of our earlier programs from which we've learned so much, You know, we've shown that the vast majority of the circulating entity, the probody therapeutic, is in masked form. And that, again, has translated into what we interpret as a successful decreasing of target engagement. So, yeah, the field's come a long way. And we're excited to see now in the hands of others these types of approaches also beginning to gain some traction. In terms of our work on EGFR CD3 and 904, we have presented – I mean, quite honestly, we haven't presented a lot of data on this program for very competitive reasons, but we did share an earlier iteration of our EGFR CD3 program with pretty extensive characterization in syngeneic animal models and in syno. And we focused in large part on the cytokine induction in those monkey studies showing a dramatic shift with the masking, dramatic shift in terms of the ability to induce cytokines. But we haven't shared a whole lot of data on the actual CX904 molecule yet. That will come in the future.
spk08: Okay, thanks. That's helpful. Thanks for taking my question. You're very welcome.
spk02: Thank you. One moment for the next question. Our next question will be coming from Anupam Rama of JPMorgan. Your line is open.
spk04: Hi. Thank you so much for taking the question. This is actually Malcolm Kuno for Anupam. What is the size and scope of the phase one dose escalation data that we should be thinking about in 2H24 for CX904? And on that, when should we get a better sense of a more granular timeline? Thank you.
spk03: Yeah, thanks for the question. So, you know, we remain on track with 904 share data in the second half as I mentioned in my prepared remarks our principal objective at this moment in time is to build the data set to share with our partner Amgen in the second half of the year and then that would result in presentation externally in an appropriate setting we we're not guiding to any specifics at this point in time obviously what we're looking for though in phase 1a is to demonstrate and really fully explore the safety profile of 904 in terms of CRS, in terms of EGFR-mediated toxicities. Obviously, look for any early evidence of anti-tumor activity. And I would expect the update in the second half, you know, it would be a meaningful number of patients, but that's really all that we're ready to say at this moment in time.
spk01: Great. Thank you.
spk02: Thank you. At this time, if you would like to ask a question, please press star 1-1 on your telephone.
spk10: There are no more questions in the queue. Thank you so much for joining the conference call today. Everyone may disconnect.
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