CytomX Therapeutics Fourth Quarter 2022 Earnings Call

March 27, 2023

Operator: Good day, 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 1, 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1, 1 again. Please be advised that today's conference is being recorded.

Speaker 2: Therapeutics, fourth quarter, 2022 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 star 11 on your telephone.

Speaker 2: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again.

Speaker 2: 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.

Please be advised that today's conference is being recorded.

Operator: I would now like to hand the conference over to your speaker for today, Chris Ogden. Please go ahead.

Chris Ogden: Thank you. Good afternoon and thank you for joining us. Before we begin, I would like to remind everyone that during this call we'll be making forward-looking statements.

Speaker 3: Before we begin, I'd like to remind everyone that during this call, we'll be making forward-looking statements.

Chris Ogden: 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.

Speaker 3: Important risks and uncertainties are set forth in our most recent public filings with the SEC at SEC.gov.

Chris Ogden: We undertake no obligation to update any forward-looking statements, whether as a result of new information, future development, or otherwise.

Chris Ogden: Earlier this afternoon, we issued a press release that includes a summary of our 2022 full year financial results and highlights recent progress at Cytomix. 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 has been filed today with the SEC.

Speaker 3: We encourage everyone to read today's press release and the associated materials, which include the 2022 10K and 2021 amended 10K, which has been filed today with the SEC.

Chris Ogden: 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.

Chris Ogden: The adjusted financial statements reflect changes in the timing of certain revenue recognition in the years from 2019 to 2022. 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.

Speaker 3: 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.

Chris Ogden: 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. With that, let me turn the call over to Sean. Thanks Chris, and good afternoon everyone. Thanks for joining us for an update on the progress at CytomX.

Sean A. McCarthy: Thanks Chris, and good afternoon everyone. Thanks for joining us for an update on the progress at CytomX.

Speaker 3: With that, let me turn the call over to Sean.

Speaker 4: progress to that cytopics. boredom

Sean A. McCarthy: On today's call, I'll provide an overview of the company's therapeutic pipeline, including status updates for our emerging programs, CX904, CX801, and CX2051. I'll also cover recent developments within our CD71 Targeting Programme and additional updates on our corporate partnerships.

Speaker 4: I'll also cover recent developments within our CD71 Targeting Programme and additional updates on our corporate partnerships.

Sean A. McCarthy: 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. Indeed, we believe that localization will be the future of biologics.

Speaker 4: Indeed, we believe that localization will be the future of biologics.

Sean A. McCarthy: 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 diseased tissue, thereby reducing systemic toxicities and maximizing overall benefit.

Speaker 4: 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 diseased tissue, thereby reducing systemic toxicities and maximizing overall benefit.

Sean A. McCarthy: 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.

Sean A. McCarthy: Since our early years, CytomX has pursued a consistent strategy focused on long-term company build around the ProBody platform and maximising 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.

Speaker 4: Our substantial investments to date have allowed for broad clinical evaluation of our platform, have resulted in a uniquely strong scientific foundation, and a strong scientific foundation. and a deep pipeline of therapeutic candidates positioned to deliver significant near and long-term value.

Speaker 4: and a deep pipeline of therapeutic candidates positioned to deliver significant near and long-term value.

Sean A. McCarthy: We currently have more than 15 active pro-body therapeutic programs including three clinical stage molecules, and expect to file two new INDs for wholly owned programs later this year.

Speaker 4: and they expect to file two new INDs for wholly owned programs later this year.

Sean A. McCarthy: 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 to 24 months.

Speaker 4: Sytoex entered 2023 with robust financial resources and funding into 2025, positioning the company to execute towards multiple milestones over the next 12 to 24 months.

Sean A. McCarthy: Moving now to our pipeline, I'd like to start with T-cell engaging biospecifics and our company's expanding efforts with this modality.

Sean A. McCarthy: 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.

Sean A. McCarthy: Localization of the powerful anti-cancer activity of this class of drugs could unlock enormous potential for patients by enhancing therapeutic windows. CytomX and our partners believe the ProBody platform to be ideally suited to addressing this challenge.

Sean A. McCarthy: Our lead program in this area is CX904, a clinical stage probody T-cell engager targeting EGFR and CD3, partnered with Amgen in a global co-developmental lens.

Sean A. McCarthy: EGFR is a highly validated and broadly expressed cancer target and we see a compelling opportunity to leverage this target to localize anti-tumor T cell responses preparatory to the tumor microenvironment.

Speaker 4: to localize anti-tumor T cell responses preparatory to the tumor microenvironment.

Sean A. McCarthy: Our published preclinical data show that a localized biospecific EGFR CD3 probody has a widened therapeutic window compared to its unmasked counterpart. These preclinical data led to the advancement of CX904, and we're now well underway with phase 1 dose of collation.

Speaker 4: These preclinical data led to the advancement of CX904, and we're now well underway with phase 1 dose of collation.

Sean A. McCarthy: The Phase 1 study has advanced from initial single patient cohorts into the 3 plus 3 phase of dose escalation. The primary goal of dose escalation for this drug candidate is to assess safety and we aim to reach those levels and exposures by the end of 2023, 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 2 dose and the potential decision to initiate Phase 1B expansion cohorts in EGFR-positive tumors.

Speaker 4: The primary goal of dose escalation for this drug candidate is to assess safety

Speaker 4: And we aim to reach those levels and exposures by the end of 2023, which we can start enrollment into backfill cohorts in certain EJFR positive tumors. Looking ahead to 2024, a key milestone on the horizon will be the selection of recommended phase 2 dose.

Speaker 4: and the potential decision to initiate Phase 1B expansion cohorts in EGFR-positive tumors.

Sean A. McCarthy: This decision will be taken in conjunction with our partner Amgen. CytomX would then be responsible for the execution of expansion cohorts and 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 CX904 updates as the program advances.

Speaker 4: Cytomics would then be responsible for the execution of expansion cohorts and upon the conclusion of the expansion phase, Amgen will take over global development with Cytomics retaining certain co-funding, co-development and co-commercialization rights. We look forward to providing additional CX904 updates as the program advances.

Sean A. McCarthy: 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.

Sean A. McCarthy: CytomX and the Astellas are also collaborating on additional T-cell engagers and CytomX is eligible to receive future preclinical, clinical, and commercial milestones across these programs. We also retain the option to select US development and commercial rights within the Astellas collaboration.

Speaker 4: We also retain the option to select US development and commercial rights within the Istellos collaboration.

Sean A. McCarthy: Continuing with T-cell biospecifics, in November 2022, CytomX sent a multi-target R&D collaboration with Regeneron to discover and develop new biospecific immunotherapies. Regeneron has considerable efforts in T-cell biospecifics 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 the therapeutic window.

Speaker 4: Regeneron has considerable efforts in T-cell bispecifics and both companies see opportunities to broaden the reach of T-cell engagers by utilizing Cytomics platform to localize these highly potent agents to tumor tissue, widening therapeutic window.

Sean A. McCarthy: 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's scientific and platform expertise.

Speaker 4: Given Regeneron's acknowledged high bar for external innovation, this collaboration is yet another point of validation of Cytomic's scientific and platform expertise.

Sean A. McCarthy: Moving now to our upcoming INDs for next generation molecules, CX2051 and CX801. Starting with CX2051 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.

Speaker 4: CX2051 and CX801. Starting with CX2051 are conditionally active probody ADC targeting EpCAM.

Speaker 4: EpCAM has been regarded as a high potential target for decades and has been clinically validated by others.

Speaker 4: but clinical activity has only been achieved with local administration.

Sean A. McCarthy: CX2051 is tailored to optimize therapeutic index for EPCAM expressing epithelial cancers by matching the target with payload mechanism of action and tumor sensitivity.

Sean A. McCarthy: We have optimized marking protease cleavability and we have selected a [inaudible] derivative, a topoisomerase 1 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 N-Hertu and Tradelvi, and we really think this payload is an optimal choice for this program.

Speaker 4: And we really think this payload is an optimal choice for this program.

Sean A. McCarthy: Although locally administered, anti-EPCAM therapeutics have shown promise, efforts to generate systemic anti-EPCAM therapeutics have to date not been successful.

Sean A. McCarthy: CX2051, 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.

Speaker 4: We anticipate filing an IND for this novel ADC in the second half of 2023.

Sean A. McCarthy: Turning now to CX801, our duly masked interferon alpha 2B, the lead program within our broad efforts in the cytokine field. We believe there's enormous potential to harness the powerful anti-cancer activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation.

Speaker 4: We believe there's enormous potential to harness the powerful anti-cancer activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation.

Sean A. McCarthy: Interferon-alpha-2B is an approved immunotherapeutic that has demonstrated clinical activity in multiple cancer types and, we believe, provides a potentially superior approach to activating anti-tumor immune responses than cytokines such as IL-2, IL-12, and IL-15.

Sean A. McCarthy: Inteferon-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.

Sean A. McCarthy: Interferon-alpha also has direct tumor cell killing activity, providing a dual mechanism of action. However, the powerful anti-cancer activity of interferon-alpha has thus far been difficult to harness due to its systemic toxicity.

Sean A. McCarthy: In data presented at CITSE 2022, we demonstrated that CX801 has a wide therapeutic index and an enhanced tolerability profile compared to unmasked interferon.

Sean A. McCarthy: Our data have highlighted CX801's preferential activity in the tumor microenvironment, as well as the potential for synergistic effects when combined with checkpoint inhibitors.

Sean A. McCarthy: We believe CX-801 has the potential to become a unique centerpiece of combination therapy for a wide range of tumor types, and 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.

Sean A. McCarthy: Let me turn now to our CD71 program. At CytomX we have had a longstanding interest in leveraging the unique molecular properties of CD71, the transferrin receptor, as an anti-cancer target. Our goal is to use our ProBody platform to open a therapeutic window for this high potential, but previously undruggable target. And as such, we have developed an antibody drug conjugate to CD71 that we call CX2029. We partnered the program with AbbVie in an alliance that dates back to 2016, and that was focused on the advancement of CX2029 into IND enabling and clinical studies.

Speaker 4: Our goal is to use our ProBody platform to open a therapeutic window for this high potential, but previously undruggable target. And as such, we have developed an antibody drug conjugate to CD71 that we call CX2029. We partnered the program with AbbVie in an alliance that dates back to 2016, and that was focused on the advancement of CX2029 into IND enabling and clinical studies.

Sean A. McCarthy: Under the collaboration agreement, CytomX was responsible for early development up to the completion of cohort expansions and with Abbvie being responsible for later stage development.

Sean A. McCarthy: We've made substantial progress since this alliance started, and in January this year we announced updated results from the cohort expansions which included encouraging clinical activity in unselected, heavily pre-treated patients with tumors of squamous histologies, including a 21% confirmed response rate in squamous esophageal cancer. K3 anemia remains the most common treatment-related adverse event. Strategies for management of anemia have included transfusions, dose delays, and dose reductions. And patients who have responded to CX2029 have been actively managed through the use of anemia mitigation measures.

Speaker 4: Strategies for management of anemia have included transfusions, dose delays, and dose reductions. And patients who have responded to CX2029 have been actively managed through the use of anemia mitigation measures.

Speaker 4: And patients who have responded to TX2029 have been actively managed through the use of anemia mitigation measures.

Sean A. McCarthy: Our January data update for CX2029 essentially marks the conclusion of CytomX's responsibilities for execution of the clinical program within the Abbvie Alliance and the data has been underevaluation at Abbvie in recent months. Abbvie informed us on March 21st that they do not plan to advance CX2029 into further clinical studies for strategic portfolio reasons and the Alliance will conclude. CytomX regains full rights to CD71 and has an exclusive option to reacquire full rights to CX2029 and these discussions are underway.

Speaker 4: And BE informed us on March 21st that they do not plan to advance TX2029 into further clinical studies for strategic portfolio reasons and the Alliance will conclude.

Speaker 4: Slitemix regains full rights to CD71 and has an exclusive option to reacquire full rights to CX2029 and these discussions are underway.

Sean A. McCarthy: 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 CX2029 while also continuing to pursue next generation strategies for targeting CD71. We would like to thank AbbVie for their partnership and helping us bring CX2029 and our CD71 program to this stage in its development.

Speaker 4: while also continuing to pursue next generation strategies for targeting CD71.

Speaker 4: We would like to thank AbbVie for that partnership in helping us bring CX2029 and our CD71 program to this stage in its development.

Sean A. McCarthy: I'd like to now briefly update on our collaborative work with Bristol-Miles Squibb and Moderna.

Sean A. McCarthy: Our alliance with BMS has continued to make progress and 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 a PulumaLab 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.

Speaker 4: We have worked with BMS on two CTLA-4 probody approaches. The first is a probody version of a PulumaLab that's called 249.

Speaker 4: We're also working with BMS on a probody version of their non-fucosylated anti-CTLA-4 designed to be a more potent version of IPI.

Speaker 4: This probody, NANE 288, is designed to be a safer, more effective version of the non-fucosylated IPI.

Sean A. McCarthy: At their 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 [inaudible] in 2022, BMS presented Phase 1 data on 218, which is the non-fucosylated antibody that underlies 288 showing intriguing activity, including microsatellite-stable colorectal cancer. The 288 Pro body is being advanced to phase 2 and we look forward to future updates from BMS.

Speaker 4: showing intriguing activity, including in microsatellite-stable colorectal cancer. The 288 Pro body is being advanced to phase 2 and we look forward to future updates from BMS.

Sean A. McCarthy: Lastly, I'd like to re-emphasize 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.

Sean A. McCarthy: 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 and we look forward to doing great things together.

Speaker 4: Cytomy and some returners 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 and we look forward to doing great things together.

Sean A. McCarthy: Let me now turn the call over to Chris to provide you with a financial overview for the quarter.

Chris Ogden: Thank you, Sean. I'm pleased to be able to share an update on our 2022 financial results with you today.

Chris Ogden: CytomX entered 2023 with a strong balance sheet with $194 million in cash, cash equivalent, and investments as of December 31, 2022, which we project will fund the operations of the company into 2025.

Chris Ogden: 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.

Chris Ogden: 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.

Chris Ogden: 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 the 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. Also, the restatement has no impact on the company's current cash position or cash flows.

Speaker 3: I would like to note that my comments regarding the financial statements refer to our most recent SEC filings, which include restated financial information.

Speaker 3: from 2019 to 2022 as a result of a change in our revenue recognition accounting method for certain collaboration agreements.

Speaker 3: The restatement impacts the timing of certain revenue recognition and does not impact total revenue that will be recognized for each collaboration.

Speaker 3: Also, the restatement has no impact on the company's current cash position or cash flows.

Chris Ogden: 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-Meyer Squid.

Chris Ogden: R&D expenses decreased by $2.5 million to $111.6 million in 2022. The decrease was primarily due to lower clinical trials 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 increased related to the company's restructuring, which was announced in July of 2022, were $7.7 million. The restructuring is substantially complete as at the end of 2022. With that, I'll turn the call back to Sean.

Speaker 3: 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 increased $3.6 million in 2022 to $4.5 million in 2022.

Chris Ogden: 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 increased related to the company's restructuring, which was announced in July of 2022, were $7.7 million. The restructuring is substantially complete as at the end of 2022. With that, I'll turn the call back to Sean.

Speaker 3: related to the company's restructuring, which was announced in July of 2022, were $7.7 million.

Speaker 3: The restructuring is substantially complete as at the end of 2022.

Sean A. McCarthy: 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.

Speaker 4: This will continue to be a year of focused execution by the company across our Partnode and wholly owned pipeline.

Sean A. McCarthy: Our progress with CX904, 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 CX801, our conditionally active interferon alpha, which is on track for IND filing this year. As we assess potential next steps for the CX2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC CX2051 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, and we remain strongly committed to our patients.

Speaker 4: conditionally active interferon alpha, which is on track for IND fighting this As we assess potential next steps for the CX2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC CX2051 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. And we remain strongly committed to our patients.

Speaker 4: As we assess potential next steps for the CX2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC CX2051 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. And we remain strongly committed to our patients.

Sean A. McCarthy: As we assess potential next steps for the CX2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC CX2051 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, and we remain strongly committed to our patients.

Speaker 4: where the highest impact applications of our technology lie for the benefit of people with cancer. And we remain strongly committed to our patients.

Sean A. McCarthy: I would like to extend my sincere thanks to the CytomX team for their ongoing dedication and commitment to our vision and mission.

Sean A. McCarthy: Operator, let's now open the call up for Q&A.

Operator: 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.

Operator: The first question we have is coming from Roger Song of Jeffries. Your line is open.

Roger Song: Great. Thank you for taking the question. 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. So 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 and what are the key criteria for you to move into the tumor-specific expansion? Thank you.

Speaker 5: So 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 and what are the key criteria for you to move into the tumor-specific expansion? Thank you. Yeah, hi, Roger. Thanks for the question. So, as I mentioned, we're pleased with the progress in the early program for 904 and the goal is the dose escalation that we're engaging in right now is really to assess safety of this very novel T-cell engager. We do believe we're on track to--

So 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 and what are the key criteria for you to move into the tumor-specific expansion? Thank you.

Sean A. McCarthy: Yeah, hi, Roger. Thanks for the question. So, as I mentioned, we're pleased with the progress in the early program for 904 and the goal is the dose escalation that we're engaging in right now is really to assess safety of this very novel T-cell engager. We do believe we're on track to-- our goal is to reach doses by the end of the year that should enable us to start backfilling cohorts as is fairly common in early phase one. With an agent like this, like any T-cell engager, to stepwise those escalations, these are highly potent molecules and 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 how to think about MTD, how to think about RP2D. So we're gonna be thoughtful here and not ready to guide to when we'll have data but we are making good progress.

Speaker 4: our goal is to reach doses by the end of the year that should enable us to start backfilling cohorts as is fairly common in early phase one. With an agent like this, like any T-cell engager, to stepwise those escalations, these are highly potent molecules and 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 how to think about MTD, how to think about RP2D. So we're gonna be thoughtful here and not ready to guide to when we'll have data but we are making good progress. Okay, that's fair. And then so in terms of your

our goal is to reach doses by the end of the year that should enable us to start backfilling cohorts as is fairly common in early phase one. With an agent like this, like any T-cell engager, to stepwise those escalations, these are highly potent molecules and 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 how to think about MTD, how to think about RP2D. So we're gonna be thoughtful here and not ready to guide to when we'll have data but we are making good progress.

Speaker 4: With an agent like this, like any T-cell engager, the stepwise those escalations, these are highly potent molecules and 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

Speaker 4: how to think about MTD, how to think about RP2D. So we're gonna be thoughtful here and not ready to guide to when we'll have data. But we are making good progress. Okay, that's fair. And then so in terms of your,

Roger Song: Okay, that's fair. And then so in terms of your

Speaker 5: upcoming R&D for AO1 in 2051. Can you just let us know what the status of the R&D enabling studies in terms of the CMC and the POC study you're doing and also... What are the initial indications for those two potential IMDs? Thank you.

Speaker 5: What are the initial indications for those two potential IMDs? Thank you.

Speaker 4: Yeah, thanks for the question. So, very excited about these two new INDs. As I've mentioned, they have broad potential across multiple tumor types. As you mentioned, Roger, the team is very busy right now with IND-enabling activities for both of these programs.

Speaker 4: We're pleased with the progress, we're on track with manufacturing steps, with toxicology programs, and everything remains on track for our guidance for these INDs being filed this year.

Speaker 4: In terms of tumor types, let's take APK-AM first. One of the things we love about this target is just how broadly expressed it is on epithelial tumors. I did...

Speaker 4: call out CRC in my comments a few moments ago, as 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 masterpiece and payload which we think is well matched.

Speaker 4: to that tumor type given the high target expression as well. But there are many other tumor types that we could potentially move into, including pancreatic, ovarian, to name just two. So many, many different areas to go. We'll be guided by what we see in phase one, of course.

Speaker 4: With regards to 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.

Speaker 4: Our strategy there with 801, given the potency of interferon alpha as an immunotherapy, is to work in the area of increasing anti-tumor immunity, turning colder tumours into warmer tumours, turning warmer tumours into hot tumours.

Speaker 4: And there'll be several opportunities to pursue there. But again, we'll be guided by the phase one dose escalation data once we get that up and running.

Speaker 5: Great. Thanks for the comment. Maybe just one last question. I will hop back on the queue. For the CD71, since you are reaping the right for this target and potentially for the entire 2029, you talk about the next generation for CD71 and we know...

Speaker 5: learning from the previous clinical data to the next generation. Thank you.

Speaker 4: Yes, that's great. Great question. And so with regard to, let's maybe start with the 2029 data. So, 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...

Speaker 4: anti-tumor activity in several tumor types and most recently this really intriguing signal in squamous esophageal. 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

Speaker 4: and mitigate anemia if we were to move 2029 forward ourselves, assuming that that was something that we ultimately decide to do. So, I think we've learned a lot with 2029 over the last couple years. There is a therapeutic window for the drug.

Speaker 4: I think it's fair to say that we believe with NextGen, we could broaden that therapeutic window. And ways to do that would be to increase the anti-tumor activity, find ways to decrease the incidence of anemia, and we have several ideas as how to do that. And I would anticipate we'll have more to say about this science as we go through the year. Great, thanks. That's it, Varna.

Speaker 2: Thank you. One moment while we prepare for our next question.

Speaker 2: And our next question is coming from Mara Goldstein of the Mitchell Hole Group. Please go ahead. Your line is open.

Speaker 6: Great. Thanks for taking that question. So just maybe to clarify a little bit on CX2029, you have rights to CD781, but you would then have to acquire the CX2029 molecule if you chose to do that. Is that correct?

Speaker 4: That's right, Mara. Yes, so the target, the program broadly, as far as the target is concerned, reverts to Cytomix, a 2029 as a Phase II asset. We have an exclusive right to negotiate full rights back from ABBE and those discussions have been initiated.

Speaker 6: Okay, and okay, fair enough. And 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?

Speaker 4: Yeah, so 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.

Speaker 4: agreement and that's the collaboration under which a couple of additional targets for ADCs were selected. And that agreement is also coming to a conclusion as well.

Speaker 6: Okay, fair enough. And then 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.

Speaker 4: off. So just to recap, the goal of the Alliance is to leverage their MRNA platform to encode and express conditionally activated biologics in oncology and non-oncology.

Speaker 4: ready to disclose additional details of the research program at this point but the collaboration is structured such that we are responsible for certain discovery and lead optimization efforts and Moderna will be responsible for development and commercialization with milestones

Speaker 4: and royalties coming to Cytomix. And so we do not expect to be involved in the development activities with Moderna, unlike for example, the relationships with Avi or even Amgen on 904. This is in some ways a more traditional discovery.

Speaker 4: relationship in which Moderna will be conducting the development of the programs as they mature and move forward. Okay all right thanks so much I appreciate it.

Speaker 4: conducting the development of the programs as they mature and move forward. Okay. All right. Thanks so much. I appreciate it. You're welcome.

Speaker 2: Thank you. One moment while we prepare for the next question.

Speaker 2: Our next question will be coming from Peter Lawson of Barclays. Your line is open. buzz weaker

Speaker 4: Hey, good afternoon, guys. Thank you for taking our question. This is actually, this is Alex on for Peter. I just have 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 one for the 218 molecule compared to the data we've seen for the 249 molecule?

Speaker 4: Yeah, happy to comment on that. So it does take a bit of time to sort of cover the various moving parts here, so just bear with me for a second, just so we're all on the same page. So 249 is the probody version of IPI.

Speaker 4: Then 218 is the non-fucosylated antibody, which is BMS's antibody. And then there's 288, which is the pro-body version of 218, the non-fucosylated. So the clinical data that BMS has presented previously relates to, as you rightly point out, to BMS.

Speaker 4: 249's phase 1 study and also the 218 phase 1 study, no data has yet been presented for 288 which is the non-coccalated probody. I would say that the key learnings from the phase 1 work on 249 and 218 are as follows. With the probody, 249, the probody version of IPI.

Speaker 4: The dose escalation was able to achieve really very high levels of the mast IPI. So they achieved 30 three zero mgs per kg of monotherapy and 15 mgs per kg in combination with full dose NEBO. And you can see how and I think it's pretty consistent with the work we've done over the years in the clinic.

Speaker 4: that the masking 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 one data, this was really the update last year at ESMO, clear evidence of clinical activity for

Speaker 4: 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.

Speaker 4: demonstrated again that 2NA, the non-pucosylated IPE is clinically active. Again, a case study was put forward in MSS CRC, which is an area where we're seeing a lot of progress by others, including agentists with their FC-enhanced TCLA4. The other...

Speaker 4: noteworthy data from the 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 it be, the non-pucosylation leads to a more potent drug and that meant that the doses administered are substantially lower than for

Speaker 4: for IPI alone. So I think that's kind of an interesting take home and 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.

Speaker 4: You know, we don't have a lot of visibility at this point in what BMS's phase two strategy will be for 288, but those are just a few thoughts from the data that's been presented thus far.

Speaker 7: Okay, great. Yeah, that makes a lot of sense. And then, yeah, just I was also curious if you have any visibility in terms of, or should we assume that the current ongoing studies, but the 249 will will sort of stop enrolling patients and.

Speaker 8: going forward and that's it. Thank you. You're welcome. Thank you one moment while we prepare for the next question.

Speaker 8: going forward and that's it. Thank you. You're welcome. Thank you. One moment while we prepare for the next question.

Speaker 3: Our next question will be coming from Mitchell Pfeffer of HC Rain. Your line is open. 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 reacquire the right.

Speaker 4: Yeah, thanks for the questions, Mitch. Can't really comment on the 2029 negotiation for obvious reasons at this point, other than to say that those discussions have been have been initiated and there's a process laid out in the contract that we negotiated some years ago for.

Speaker 4: for how to go about that. So we'll see where it all goes. With regards to esophageal, it is really interesting to us, the signal that we've seen there. One of the...

Speaker 4: One of the intriguing features of esophageal that relates to the target is published data from others showing or suggesting that CD71 is amplified in certain squamous esophageal tumors. Given the

Speaker 4: So, you know, one could certainly imagine that there is a relationship between target level or more specifically target amplification and clinical activity. And that is something that we're aggressively pursuing as, you know, to figure out whether there's a potential patient selection strategy there. But speaking in it.

Speaker 4: general terms, of course, given the high incidence of anemia that we have with this drug, but also given its clinical activity, if we elect to move the drug forward in esophageal, let's say,

Speaker 4: 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. So that's something that we're actively looking at that relates to the

Speaker 2: Annal-Tam Rama of JPMorgan. Your line is open.

Speaker 9: Hi, thank you for taking the question. This is actually Malcolm Kunilhan for Anupam. Just one quick question. So given that some of your collaborations involve cost sharing agreements, what should we assume as being baked into your cash runway?

Speaker 10: I'll pass that one over to Chris. Yeah. Hi Malcolm. Just to reiterate what we've communicated on Cash Frontway in the prepared remarks. We reported 194 million of cash at the end of the year. As I mentioned, that does not include

Speaker 10: the Moderna upfront payment of 35 million received in Q1 of 2023, nor the the Estellas milestone that we achieved of 5 million in January of this year. In terms of color on the guidance, we don't you know...

Speaker 10: Go into specifics on exactly what's what's assumed, you know, from a overall capital allocation and resource resourcing perspectives. You know, we communicated in the summer of last year. You know, the focus on CX 904. And the next generation pipeline.

Speaker 10: So, of course, capital will be allocated to those programs as appropriate, but beyond. Beyond that, we're not giving additional color. Yeah. Just one quick addition there in terms of the...

Speaker 4: the deal structures, again as we mentioned in the comments earlier, both the AbbVie and Gen Alliances have been structured in a way that with AbbVie we had, I guess now we're obviously concluding that relationship.

Speaker 4: but we had and with Anja we have.

Speaker 4: the opportunity to invest in later stage development, but that's quite a bit further down the road. So as Chris mentioned, you know, current...

to invest in later stage development, you know, but that's quite a bit further down the road. So, as Chris mentioned, you know, current

financials and guidance is really focused on advancing the early stage programs to key near-term milestones. That makes sense. Thank you. Thank you. One moment while we prepare for the next question.

The next question is coming from Edgar Durott of BMO. Your line is open.

Great, thanks for taking a question. Just wanted a clarifying question on the Pro-Body 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...

which we now know are fairly notorious. If you could maybe talk a little bit about that as well. Thank you.

Yeah, thanks, Esther. Obviously, questions would be probably more comprehensively answered by our partner, BMS, but let me just make a couple brief comments. So, first of all, with regards to the 288 leapfrog, as you put it, we have a lot of questions

You know, they have been pretty clear that they have prioritized 288 over the other programs and the advancement from phase 1 to phase 2 reflects that. I think if one looks at the broad landscape of CTLA-4 next-gens that are being pursued by

by various parties, there is a move towards more potent versions of anti-CTL4 antibodies using strategies like Fc enhancement or in the case of BMS non-Pucosylation which are functionally more potent actually.

Very similar. So, their decision, I think, looking at it from the standpoint of the outside world and the way the field is evolving,

make 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, the target biology, is less well tolerated. I think the profile though of adverse events that are seen are similar.

So I don't, I'm not aware of anything that's particularly unique with the EFC-enhanced, but would have to study the data a bit more closely. China, thank you for the update. Yeah, and the goal of the pro body, of course, is to...

is to open that therapeutic window and that's why we're encouraged that they prioritize 288. Got it. Yep. Thank you. You're welcome. 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.

I have.

The.

by the next.

Therapeutics, fourth quarter, 2022 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 star 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 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.

Thank you. Good afternoon and thank you for joining us. Before we begin, I'd 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 2022 full year financial results and highlights recent progress at Cytomix.

We encourage everyone to read today's press release and the associated materials, which include the 2022 10K and 2021 amended 10K, which has 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 SDC filings today. The adjusted financial statements reflect changes in the timing of certain revenue recognition in the years from 2019 to 2022. Additionally, the press release of the SDC filings is not a recommendation for the SDC. The SDC filings reflect changes in the timing of certain revenue recognition in the years from 2019 to 2022. The adjusted financial statements reflect changes in the years from 2019 to 2022.

A recording of this call and our SEC filings can be found under the investors and do section of our website. With me on the call today is Dr. Sean McCarthy, Cytomics' Chief Executive Officer and Chairman.

Sean will provide a business and pipeline update before I walk through the financials for 2022. With that, let me turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. Thanks for joining us for an update on recent progress at Cytomics. On today's call, I'll provide an overview of the company's therapeutic pipeline, including status updates for our emerging programs, CX904, CX801, and CX2051.

I'll also cover recent developments within our CD71 targeting program and additional updates on our corporate partnerships. At Cytomics 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.

Indeed, we believe that localization will be the future of biologics. Playtonic'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 is an important year of transition for our company, in which we restructured and repositioned Cytomix 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, Cytomix has pursued a consistent strategy focused on long-term company build around the ProBody platform and maximising 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 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 pro-body 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.

Cytomics entered 2023 with robust financial resources and funding into 2025, positioning the company to execute towards multiple milestones over the next 12 to 24 months. Moving now to our pipeline, I'd like to start with T-cell engaging biospecifics and our company's expanding efforts with this modality. T-cell engagers hold tremendous promise for the treatment of solid tumors.

Our lead program in this area is CX904, a clinical stage, pro-body T-cell engager targeting EGFR and CD3, partnered with Amgen in a global co-developmental lens.

EGFR is a highly validated and broadly expressed cancer target and we see a compelling opportunity to leverage this target.

to localize anti-tumor T cell responses preferentially to the tumor microenvironment. Our published preclinical data show that a localized bispecific EGFR CD3 pro-body has a widened therapeutic window compared to its unmasked counterpart. These preclinical data led to the advancement of CX904.

and we're now well underway with phase one dose escalation. The phase one study has advanced from initial single patient cohorts into the three plus three phase of dose escalation. The primary goal of dose escalation for this drug candidate is to assess safety, and 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 2 dose and the potential decision to initiate phase 1b expansion cohorts in EGFR-positive tumours. This decision will be taken in conjunction with our partner Amgen.

Cytomics would then be responsible for the execution of expansion cohorts and upon the conclusion of the expansion phase, AMGEN will take over global development with Cytomics retaining certain co-funding, co-development and co-commercialization rights. We look forward to providing additional CX904 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 Cytomics.

Cytomics and the Stellis are also collaborating on additional T-cell engagers and Cytomics is eligible to receive future preclinical, clinical, and commercial milestones across these programmes.

We also retain the option to select US development and commercial rights within the Istellus collaboration. Continuing with T-cell bispecifics in November 2022, Cytomic sent 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...

Given Regeneron's acknowledged high bar for external innovation, this collaboration is yet another point of validation of cytonic scientific and platform expertise.

Moving now to our upcoming IDs for next generation molecules, CX2051 and CX801.

Starting with CS2051, our conditionally active ProBody ADC targeting EpCAM.

F-CAM 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.

CX2051 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 marking protease cleavability and we have selected a cancer thesin derivative, a topoisomerase 1 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 NhR2 and Tridelvi and we really think this payload is an optimal choice for this program.

Although locally administered anti-epam therapeutics have shown promise, efforts to generate systemic anti-epam therapeutics have to date not been successful. CX2051, however, when systemically administered, has demonstrated a wide predicted therapeutic index and strong preclinical activity in multiple preclinical models, including colorectal cancer. I anticipate filing an IND for this novel ADC.

in the second half of 2023. Turning now to CX801, our duly masked interferon alpha 2B, the lead program within our broad efforts in the cytokine field.

We believe there's enormous potential to harness the powerful anti-cancer activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation. Interferon Alpha-2b is an approved immunotherapeutic that has demonstrated clinical activity.

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 anti-cancer activity of interferon-alpha has thus...

Our data have highlighted CX801's preferential activity in the tumor microenvironment, as well as the potential for synergistic effects when combined with checkpoint inhibitors. We believe CX801 has the potential to become a unique centerpiece of combination therapy for a wide range of tumor types, and we aim to rapidly advance this potentially best-in-class program.

unique molecular properties of CD71, the transferrin receptor, as an anti-cancer target.

Our goal is to use our ProBody platform to open a therapeutic window for this high potential, but previously undruggable target. And as such, we have developed an antibody drug conjugate to CD721 that we call CX2029.

We partnered the program with AbbVie in an alliance that dates back to 2016 and that was focused on the advancement of CX2029 into IND enabling and clinical studies.

Under the collaboration agreement, Slikomics was responsible for early development up to the completion of cohort expansions and with that being responsible for later stage development.

We've made substantial progress since this alliance started and 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. A3 anemia remains the most common treatment-related adverse event.

Strategies for management of anemia have included transfusions, dose delays, and dose reductions, and patients who have responded to TF2029 have been actively managed through the use of anemia mitigation measures.

Our January data update for CX2029 essentially marks the conclusion of cytonics responsibilities for execution of the clinical program within the AbbVie Alliance, and the data has been under evaluation at AbbVie in recent months.

And V informed us on March 21st that they do not plan to advance CX2029 into further clinical studies for strategic portfolio reasons, and the alliance will conclude. Cytomics regains full rights to CD71 and has an exclusive option to reacquire full rights to CX2029, and 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. Looking forward, Cytermix will be evaluating next steps for CX2029.

while also continuing to pursue next generation strategies for targeting CD71. We would like to thank AbbVie for their partnership in helping us bring CX2029 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 and 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 programs.

body 288, which is now the leading edge of their next generation's CTLA-4 program.

But since the end of 2022, BMS presented phase 1 data on 218, which is the non-Fucosylated antibody that underlies 288, showing intriguing activity, including in microsatellite-stable colorectal cancer. At this point, it's time to Kellypirate.

The 288 Pro body is being advanced to Phase 2 and we look forward to future updates from BMS. Lastly, I'd like to re-emphasize our most recent collaboration with Moderna, which highlights Cytomics' 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.

Cytomy and some returners 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 and 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. Thank you, Sean. I'm pleased to be able to share an update on our 2022 financial results with you today.

Cytomix entered 2023 with a strong balance sheet with $194 million in cash, 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 Cytomix'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. Also, 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-Meyer-Squid. R&D expenses decreased by $2.5 million to $111.6 million in 2022. The decrease was primarily due to lower clinical trials 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, increased $3.6 million in 2022.

or $7.7 million. The restructuring is substantially complete as at the end of 2022.

With that, I'll turn the call back to Sean. Thanks, Chris. In summary, Cytomics 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 CX904, 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 CX801, our conditionally active interferon alpha, which is on track for IND filing this year. As we assess potential next steps for the CX2029 asset,

and our CD71 program more broadly, we're also excited to advance our latest ADC CX2051 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. And we remain strongly committed to our patients. I would like to extend my sincere thanks to the Cytomics team for their ongoing dedication and commitment to our vision and mission.

program more broadly, we're also excited to advance our latest ADC CX2051 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 and we remain strongly committed to our patients. I would like to extend my sincere thanks to the Cytomics team for their ongoing dedication and commitment to our vision and mission. Operator, let's now open the call up for Q&A.

Thank you. As a reminder, if you would like to ask a question, please press star 11 on your telephone. One moment while we compile the Q&A roster. The first question we have is coming from Roger Song of Jaffries. Your line is open. Great. Thank you for taking the question. 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 to the expansion next year.

So can you just give us some kind of a comment around what should we expect to see in terms of the data state from that program, and what are the key criteria for you to move into the tumor-specific expansion? Thank you. Yeah, hi, Roger. Thanks for the question. So as I mentioned, we're pleased with the progress in the early program for 904 and the goal of the dose escalation that we're engaged in right now is really to assess safety.

this very novel T cell engager and you know 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 it's fairly common in early phase one

With an agent like this, like any T-cell engager, you know, the stepwise those escalation, these are highly potent molecules and 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 optimists and how to think about MTD, how to think about RP2D.

So, you know, we're going to be thoughtful here and not ready to guide to when we'll have data, but we are making good progress.

Okay, that's fair. And then so in terms of your upcoming R&D for AO1 and 2051, can you just let us know what the status of the R&D enabling studies in terms of the CNC and the Output mapping for joke Izzy B has a question that you want to take advantage of?

talk about your team and also what are the initial indications for those two potential INDs. Thank you. Yeah thanks for the question. So very excited about these two new INDs. As I've mentioned they have broad potential across multiple tumor types. The

And as you mentioned, Roger, the team is very busy right now with IND-enabling activities for both of these programs. We're pleased with the progress, we're on track with manufacturing steps, with toxicology.

programs and everything remains on track for our guidance for these INDs being filed this year. In terms of tumor types, let's take APM 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 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...

to name just two, so many, many different areas to go. We'll be guided by what we see in phase one, of course. With regards to 801, interferon has been approved in several tumor types in the past, where we already know it's an active drug, it's an approved drug. Our strategy there with 801, given the potency of interferon alpha as an immunotherapy.

is to work in the area of increasing anti-tumor immunity, turning colder tumors into warmer tumors, turning warmer tumors into hot tumors, and there'll be several opportunities to pursue there. But again, we'll be guided by the phase one dose escalation data once we get that up and running. Great, thanks for the comment. Maybe just one last question, I will hop back on the queue.

is for the CD71, since you are reading the right for this target and potentially for the entire 2029. So you talk about the next generation for CD71, and we know the linear is on target, kind of for probability finding you have been observing.

So, can you just let us know what are the key strategies for the next generation and how you're going to apply from the learning from the previous clinical data to the next generation? Thank you.

Yes, that's great. Great question. And so with regard to, let's maybe start with the 2029 data. So, 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

anti-tumor activity in several tumor types and most recently this really intriguing signal in 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. So, you know, we've learned a lot with 2.029 over the last couple years. There is a therapeutic window for the drug. I think it's fair to say that we believe with NextGen we could broaden that therapeutic window. And different ways to do that would be to increase the anti-tumor activity, uh...

find ways to decrease the incidence of anemia and we have several ideas as how to do that and I would anticipate we'll have more to say about this science as we go through the year. Great, thanks. That's it for Anna.

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

Great. Thanks for taking that question. So just maybe to clarify a little bit on CX2029, you have rights to CD781, but you would then have to acquire the CX2029 molecule if you chose to do that. Is that correct?

That's right, Mara. Yes, so the target, the program broadly, as far as the target is concerned, reverts to Cytomics, a 2029 as a Phase II asset. We have an exclusive right to negotiate full rights back from ABBYY and those discussions have been initiated.

Okay, and okay, fair enough. And 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?

Yeah, so 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 and that's the collaboration under which...

A couple of additional targets for agencies were selected and that is also coming to a conclusion as well.

Okay, fair enough. And then 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 see?

excited we are about the science that we're doing with Moderna that we've just kicked off. So just to recap, the goal of the Alliance is to leverage their mRNA platform to encode and express conditionally activated biologics in oncology and non-oncology.

ready to disclose additional details of the research program at this point, but the collaboration is structured such that 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 Cytomix. And so we do not expect to be involved in the development activities with Moderna.

Unlike, for example, the relationships with AVI 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. Okay. All right. Thanks so much. I appreciate it. You're welcome. Thank you. Thank you.

Our next question will be coming from Peter Lawson of Barclays. Your line is open. 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?

just so we're all on the same page. So 249 is the probody version of IPI. Then 218 is the non-fucosylated antibody, which is the MS's antibody. And 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 1 study and also the 218 Phase 1 study. No data has yet been presented for 288, which is the non-coccalated probody. I would say that the key learnings from the Phase 1 work on 249 and 218 are as follows. With the probody, 249, the probody version of IPI,

The dose escalation was able to achieve really very high levels of the mast IPI. So they achieved 30 3-0 mgs per kg of monotherapy and 15 mgs per kg in combination with full-dose NEBO. And you can see how, and I think it's pretty consistent with the work we've done over the years in the clinic.

that the masking 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 1 data, this was really the update last year at ESMO, clear evidence of clinical activity for 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 2,1,8, the non-pucosylated IPP is clinically active. Again, a case study was put forward in MSS CRC, which is an area where we're seeing a lot of progress by others, including agentists with their FC-enhanced TCLA4. The other noteworthy data from the 2,1,8 poster is that this drug, you can see how it's a lot more potent than the other 2,1,8 poster.

is designed to be more potent than IPP, then autocosylation leads to a more potent drug and that meant that the doses administered are substantially lower than for for IPP alone. So I think that's kind of an interesting take home and the prioritization of 2-8-8, the masked version of that 2-1-8, I would think has the potential to be more potent than for IPP alone.

to evaluate higher doses of the non-tucosylated in mask form. So, you know, we don't have a lot of visibility at this point in what BMS's phase 2 strategy will be for 288, but those are just a few thoughts from the data that's been presented thus far.

Okay, great. That makes a lot of sense. And 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 249 will sort of stop enrolling patients going forward. And that's it. Thank you.

You're welcome. Thank you. One moment while we prepare for the next question. Our next question will be coming from.

Mitchell Paphor of HC Rainwright, your line is open.

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 reacquire the rights. What does that entail? And then 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? Yeah, thanks for the questions, Mitch. Can't really comment on the 2029 negotiation for obvious reasons at this point, other than to say that those discussions have been have been initiated and there's a process laid out in the contract that we negotiated some years ago for her.

for how to go about that. So we'll see where it all goes. With regards to esophageal, it is really interesting to us, the signal that we've seen there. One of the

One of the intriguing features of esophageal that relates to the target is published data from others showing or suggesting that CD71 is amplified in certain squamous esophageal tumors. found at a speed sensor.

So, you know, one could certainly imagine that there is a relationship between target level or more specifically target amplification and clinical activity. And that is something that we're aggressively pursuing as, you know, to figure out whether there's a potential patient selection strategy there. That's speaking in.

general terms, of course, given the high incidence of anemia that we have with this drug, but also given its clinical activity, 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. So that's something that we're actively looking at that relates directly to the target. Okay, great. Thank you very much for taking my questions.

increase the likelihood of response, and also, of course, continue to work to find ways to manage and mitigate anemia to give the drug its best chance of future success. So that's something that we're actively looking at that relates directly to the target. OK, great. Thank you very much for taking my questions. You're welcome.

Thank you. One moment while we prepare for the next question. Next question will be coming from Anupam Rama of J.P. Morgan. Your line is open. Hi, thank you for taking the question. This is actually Malcolm Kunilhan for Anupam. Just one quick question. So given that some of your collaborations involve cost sharing agreements, what should we assume as being baked into your cash runway? I'll pass that one over to Chris. 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 Asellus milestone that we achieved of 5 million in January .

of this year. In terms of color on the guidance, we don't go into specifics on exactly what's assumed. From an overall capital allocation and resourcing perspective, we communicated in the summer of last year the focus on CX-904 and the next generation pipeline.

So, of course, capital will be allocated to those programs as appropriate, but beyond. Beyond that, we're not giving additional color. Yeah. Just one quick addition there in terms of the.

the deal structures, again as we mentioned in the comments earlier, both the AVVN and GEN alliances have been structured in a way that we, with AVVN we had, I guess now we're obviously concluding that relationship but we had and with ANGEN we have.

the opportunity to invest in later stage development, you know, but that's quite a bit further down the road. So, so, as Chris mentioned, you know, current financials and guidance is really focused on advancing the early stage programs to key near-term milestones. That makes sense. Thank you. Thank you.

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. And then if you could maybe speak to sort of maybe the…

the safety tolerability differences potentially between 218, the antibody from Bristol, and the IPE sort of AE profile, which we now know are fairly notorious. If you could maybe talk a little bit about that as well. Thank you.

the safety tolerability differences potentially between 218, the antibody from Bristol and the, you know, IPE 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. Yeah, thanks, Esther.

Obviously, questions would be more comprehensively answered by our partner, BMS, but let me just make a couple of brief comments. So, first of all, with regard to the 288 leapfrog, as you put it, they have been pretty clear that they have prioritized 288 over the other programs and the advancement from phase 1 to phase 2 reflects that.

I think if one looks at the broad landscape of CTLA-4 next-gens that are being pursued by various parties, there is a move towards more potent versions of anti-CTLA-4 antibodies using strategies like...

FCA enhancement, or in the case of BMS, the non-pucosylation, which are functionally very similar. So,

or in the case of BMS, non-pucosylation, which are functionally very similar. So if....

their decision, I think looking at it from the standpoint of the outside world and the way the field is evolving, makes sense to us. With regard to safety of 2.1.8, again I think the question we'd 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, the target biology, is less well tolerated. I think the profile though of adverse events that are seen are similar. So I'm not aware of anything that's particularly unique.

with DFC enhanced, but would have to study the data a bit more closely. Thank you for the update. Yeah, and the goal of the pro body of course is to open that therapeutic window and that's why we're encouraged that they prioritize 288.

Got it. Yep. Thank you. You're welcome. Thank you.

CytomX Therapeutics Fourth Quarter 2022 Earnings Call

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