Q1 2024 CytomX Therapeutics Inc Earnings Call

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Speaker Change: Good day, and thank you for standing by walking through the <unk> Therapeutics first quarter 2024 financial results Conference call.

Operator: Good day, and thank you for standing by. Welcome to the CytomX Therapeutics first quarter 2024 financial results conference call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session, and to ask a question during the session, you will need to press * one on your telephone, and you will then hear an automated message advising your hand is raised.

Operator: To withdraw a question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to our speaker today, Chris Ogden, CytomX's Senior Vice President, Finance and Accounting. Please go ahead.

At this time all participants are in a listen only mode.

After the speaker's presentation, there will be a question and answer session and to ask a question. During the session you will need to press star one want all gets household annual down here, an automated message advice senior had this race.

Jerry a question. Please press star one one again.

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

I would now like to hand, the conference over to your Speaker today, Chris Ogden Cytolysis Senior Vice President Finance It accounting. Please go ahead.

Christopher W. Ogden: Thank you good afternoon, and thank you for joining us.

Christopher W. 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 will be making four 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.

Christopher W. Ogden: Before we begin I would like to remind everyone that during this call we will be making forward looking statements.

Christopher W. Ogden: Because forward looking statements relate to the future theyre subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control.

Christopher W. Ogden: 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 included a summary of our first quarter 2024 financial results and highlights recent progress at CytomX. We also issued a press release today announcing positive initial Phase 1a dose escalation data for monotherapy CX904, which will be the primary focus of today's call.

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.

Christopher W. Ogden: Earlier. This afternoon, we issued a press release that includes a summary of our first quarter 2024 financial results and highlight recent progress at <unk>.

Christopher W. Ogden: We also issued a press release today announcing positive initial phase Iia dose.

Christopher W. Ogden: Relation data for monotherapy CX 904.

Speaker Change: Which will be the primary focus of today's call.

Christopher W. Ogden: We encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC.

Christopher W. Ogden: We encourage everyone to read today's press releases and the associated materials which have been filed with the SEC. Additionally, the press releases or according to this call and our SEC filings can be found under the investors and news section of our website.

Speaker Change: Additionally, the press releases or recording of this call and our SEC filings can be found under the investors and news section of our website.

Christopher W. Ogden: With me on the call today are Dr. Sean Mccarthy.

Christopher W. Ogden: With me on the call today are Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman, and Dr. Wayne Chu, CytomX's Chief Medical Officer. Sean will provide an update on the overall pipeline and also outline CytomX's broader strategy for mass T-cell engagement. Wayne will then give an update on the CX904 Phase 1 Dose Escalation Study before Sean provides closing comments, and we open up the call for Q&A. With that, I'll now turn the call over to Sean. Thanks, Chris. And good afternoon, everyone.

Speaker Change: Thomas <unk>, Chief Executive Officer and Chairman.

Wayne Chu: And Dr Wayne Chu.

The Chief Medical Officer.

Speaker Change: Sean will provide an update on the overall pipeline and also outlines the topics as broader strategy for math T cell engagements.

Wayne Chu: Wayne will then give an update on the CX 904 phase one dose escalation study before Sean provide closing comments and we open up the call for Q&A.

Sean A. McCarthy: With that I'll now turn the call over to Sean.

Sean: Thanks, Chris and good afternoon, everyone. It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our phase one study of our Egfr targeted priority T cell engages CX 904.

Sean A. McCarthy: It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our Phase 1 study of our eGFR-targeted probody T-cell engager, CX904. CytomX is highly focused on addressing major unmet needs in oncology using our ProBody Therapeutic Platform, a proprietary antibody masking strategy designed to improve the therapeutic window for multiple antibody modalities through tumor localized activation We are leveraging our ProBody therapeutic platform to discover and develop new cancer therapies based on masked T-cell engagers, masked ADCs, and masked cytokines.

Sean A. McCarthy: Secondly, <unk> is highly focused on addressing major unmet needs in oncology using our <unk> therapeutic platform, our proprietary antibody masking strategy designed to improve the therapeutic window for multiple antibody modalities through tumor localized activation.

Sean: We are leveraging our <unk> therapeutic platform to discover and develop new cancer therapies based on masked T cell engages masked adcs and mask cytokines.

Sean: Our broad and deep pipeline encompasses more than 15 active programs, including three clinical stage molecules and significant retained commercial rights.

Sean A. McCarthy: Our broad and deep pipeline encompasses more than 15 active programs, including three clinical stage molecules and significant retained commercial rights. Strategic partnering has been a long-standing component of our corporate strategy, and we're proud to be working closely with Bristol-Myers Squibb, Amgen, Astellas, Regeneron, and Moderna on multiple pro-body therapeutic programs. We continue to be in a strong financial position with 150 million dollars of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding.

Sean: Strategic partnering because we are a long standing components of our corporate strategy and we're proud to be working closely with Bristol Myers Squibb, Amgen, Astellas Regeneron and Mcdonough on multiple priority therapeutic programs.

Sean: We continue to be in a strong financial position with $150 million of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding.

Sean A. McCarthy: CytomX is very strong organizationally, with integrated R&D capabilities, continued investment in our core technology, and a deeply experienced team dedicated to our vision of transforming lives with safer, more effective therapies. Moving to slide six, the CytomX product design strategy using our ProBody therapeutic platform is informed by more than a decade of experience and seeks to balance target selection, masking strategy, and effective function to make meaningful impact in key areas of unmet need in oncology.

Sean: So that makes us very strong organizationally with integrated R&D capabilities continued investment in our core technology and a deeply experienced team dedicated to our vision of transforming lives with safer more effective therapies.

Sean: Moving to slide six the cytogenetics product design strategy using our priority therapeutic platform is informed by more than a decade of experience and seeks to balance target selection marketing strategy and effector function to make meaningful impact in key areas of unmet need in oncology.

Sean A. McCarthy: CX904 brings the EGFR target together with T-cell engagement via CD3 with the goal of T-cell-mediated killing of EGFR-positive tumor types, potentially including those for which conventional antibodies have not shown activity. CX2051 is our masked, conditionally activated ADC that integrates the high potential of Epcam as a cancer cell target with the potency of a Topo1 inhibitor payload, ideally suited, we believe, to high Epcam-expressing tumors like colorectal cancer.

Sean: CX 904 brings the Egfr target together with T cell engagement <unk> three with the goal of T cell mediated killing of Egfr positive tumor types potentially including those for which conventional antibodies have not shown activity.

Sean: CX 2051 is a marked conditionally activated ADC that integrates the high potential of <unk> as a cancer cell target with the potency of a total one inhibitor payload ideally suited we believe to hi, <unk> expressing tumors like colorectal cancer.

Sean A. McCarthy: <unk> <unk> hundred one leverages the potent activity of the cytokines interferon Alpha which in this case is the effective mechanism itself.

Sean A. McCarthy: CX801 leverages the potent activity of the cytokine interferon alpha, which in this case is the effector mechanism itself. Our master interferon is designed to locally activate the intratumoral immune microenvironment with potential to drive responses across multiple cancer types, including melanoma, renal cell carcinoma, and head and neck squamous cell carcinoma. Q1 was an extremely productive quarter for CytomX. We are executing on our plans, and we're making progress across the full breadth of our pipeline. Today, we're announcing positive initial Phase 1a dose escalation data for Monotherapy CX904, our EGFR-CD3 T-cell engager in solid tumors, and this is the main topic of our update here today.

Sean A. McCarthy: <unk> is designed to locally activate the intra tumoral immune microenvironment with potential to drive responses across multiple cancer types, including melanoma renal cell carcinoma in head and neck squamous cell carcinoma.

Sean A. McCarthy: Q1 was an extremely productive quarter. Besides <unk>, we are executing to our plans and we're making progress across the full breadth of our pipeline.

Sean A. McCarthy: Today, we are announcing positive initial phase one dose escalation data from monotherapy CX 904, our Egfr CD three T cell engagement in solid tumors and this is the main topic of our update here today.

Sean A. McCarthy: In addition to our exciting progress with CX 904 during Q1, the first dose cohort in the phase one clinical study of 205, one our ADC targeting <unk>. This study is focused largely in colorectal cancer and we anticipate initial data in the first half of 2025.

Sean A. McCarthy: In addition to our exciting progress with CX904, during Q1, the first dose cohort cleared in the Phase 1 clinical study of 2051, our ADC-targeting EPCAM. This study is focused largely on colorectal cancer, and we anticipate initial data in the first half of 2025. Also, during Q1, Phase 1 study initiation activities continued for CX801, Mast Interferon Alpha, including the execution of an agreement with Merck to supply Keytruda for combination with CX801, and we announced that agreement last night. Initial data from the 801 program is also anticipated in 2025.

Sean: Also during Q1 phase one study initiation activities continued for CX 801.

Sean: Interferon alpha, including the execution of an agreement with Merck to supply Keytruda for combination with CLSA, Taiwan, and we announced that agreement last night.

Sean: Initial data from the 801 program is also anticipated in 2025.

Sean: We continue to make excellent progress across our collaborations, including earning $10 million of milestones under our T cell engaging by specific caliber collaboration with Astellas.

Sean A. McCarthy: We continue to make excellent progress across our collaborations, including earning $10 million in milestones under our T-Cell Engaging by Specific collaboration with Astellas, which was for preclinical progress on the first two programs in the Alliance. We're also delighted to welcome Dr. Zhen Su to our board during Q1. So a really productive start to 2024 for CytomX on all fronts, and our current clinical pipeline is really gaining momentum. And we have a very exciting 12 to 24 months ahead of us.

Sean A. McCarthy: That was for preclinical progress on the first two programs in the alliance.

Dr Sue: We're also delighted to welcome Dr Sue to our board.

Sean: During Q1, so it really productive start to 2024 proprietary mix on all fronts.

Sean: Current clinical pipeline is really gaining momentum and we have a very exciting 12 to 24 months ahead of us.

Sean: Moving now to our T cell engagement strategy.

Sean A. McCarthy: Moving now to our T cell engages strategy. T cell engagement by specific antibodies, of course, has enormous potential for the treatment of cancer and first demonstrated meaningful clinical benefit in hematologic malignancies. Looking at the solid tumor landscape for T cell engages, however, it's taken time to see meaningful clinical progress.

Sean: T cell engaging bi specific antibodies of course have enormous potential for the treatment of cancer.

Sean: First demonstrated meaningful clinical clinical benefit in hematologic malignancies.

Sean: Looking at the solid tumor landscape for T cell engages however, it has taken time to see meaningful clinical progress and for this modality to really breakthrough in solid tumors. There is some significant challenges to overcome.

Sean A. McCarthy: And for this modality to really break through in solid tumors, there are some significant challenges to overcome. Notably, T cell engagement brings very high potency, and this potency can lead to toxicities in normal tissues where the tumor molecule of interest may also be present. Another key limitation for T cell engagement in solid tumors is cytokine release syndrome, resulting from systemic binding to CD3 on T cells and also neurotoxicity in the form of ICAT.

Sean: It's a <unk> T cell engagements bring very high potency in this potency can lead to toxicities in normal tissues, where the tumor ratcheted of interest may also be present.

Sean: Another key limitation for T cell engages in solid tumors as cytokine release syndrome, resulting from systemic binding to <unk> on T cells and also neurotoxicity in the form of icons.

Sean A. McCarthy: At <unk>, we have a broad based program focused on masking T cell engages to decreased tumor antigen binding of normal tissues and also decreased CD three binding in the periphery, thereby improving therapeutic index.

Sean A. McCarthy: At CytomX, we have a broad-based program focused on masking T cell engagers to decrease tumor antigen binding in normal tissues and also decrease CD3 binding in the periphery, thereby improving therapeutic index. In addition to our internal programs, we're working with partners Amgen, Astellas, Regeneron, and BMS in this exciting space. CX904 is our lead program in the T-cell engager area, and I'd like to spend a few minutes now walking through the history and structure of this molecule.

Sean A. McCarthy: In addition to our internal programs, we are working with partners Amgen Astellas Regeneron and BMS in this exciting space.

Sean: 900, <unk> is our lead program in the T cell engage area I'd like to spend a few minutes walking through the history and structure of this molecule.

Sean: We've had a longstanding interest in Egfr <unk> are seminal publication of the first.

Sean A. McCarthy: We've had a longstanding interest in EGFR at CytomX; our seminal publication of the first ever successful antibody masking was focused on the EGFR binding antibody cituximab, for which we showed a marked reduction in systemic skin rash for the masked antibody compared to the unmasked version. These findings set the stage for the evolution of the monospecific EGFR probody into our CX904 bispecific T-cell engager.

Sean: However, successful antibody masking was focused on.

Sean A. McCarthy: On the Egfr binding antibody cetuximab, but which we showed a marked reduction in systemic skin rash for the Mazda antibody compared to the unmasked version.

Sean: These findings set the stage for the evolution of the mono specific Egfr pro body into our CX 904 bi specific T cell engagements. We reason that Egfr is a target has so much more potential to be realized.

Sean A. McCarthy: We reason that EGFR as a target has so much more potential to be realized and that realization of this potential would require a more potent effector mechanism, leading us to the concept of the MAF EGFR CD3 strategy encompassed in CX904. We did actually publish an early lead molecule from this program in cancer research to demonstrate preclinical proof of concept, and we subsequently refined the structure using the depth of our platform and in collaboration with our partner Amgen. The next slide shows the molecular architecture of 904. CX904 has one CD3 binding domain and one EGFR binding domain. Both domains are masked by unique peptides.

Sean: And the realization of this potential would require a more potent effective mechanism leading us to the concept of the mass Egfr CD three strategy encompassed in CX 904.

Sean A. McCarthy: Furthermore, the protease-cleavable substrates are different in each binding domain, reflecting our preclinical fine-tuning strategy for optimization of the therapeutic window. CX904 also has an FC region, and so it would be expected to have an antibody-like half-life. This overall structure is somewhat similar to Amgen's tarlatumab, which has shown impressive results in small cell lung cancer. Shown on the right of this slide is a recap of the therapeutic concept for CX904 and for our platform generally. The concept is that masking reduces drug binding to targets in normal tissues, whereas in tumor tissues, the masks are removed by activated tumor protease.

Sean: Actually publish an early lead molecule from this program in cancer research to demonstrate preclinical proof of concept and we subsequently refined the structure using the depth of our platform and in collaboration with our partner Amgen.

Sean: The next slide shows the molecular architecture Augmentin 046.

Sean: CX 904 has one CD three binding domain and one egfr binding domain. Both domains are masked with unique peptides. Furthermore, the protease cleavable substrates are different and each binding domain, reflecting our preclinical fine tuning strategy for optimization of therapeutic window.

Sean A. McCarthy: CX 904 also has an FC region. So it would be expected to have an antibody like half life.

Sean A. McCarthy: This overall structure is somewhat similar to amgen's <unk>.

Sean A. McCarthy: As shown impressive results in small cell lung cancer.

Sean: Shown on the right of this slide is a recap of the therapeutic concept for CX 904 and for our platform generally.

Sean: The concept is that marketing reduces drug binding to target in normal tissues, whereas in tumor tissue damasio removed by activated tumor proteases distributor.

Sean: <unk> localization these to the improvement or creation of a therapeutic window.

Sean: For the Egfr CD three <unk>, it's been shown previously that the unmarked by specific is highly toxic in preclinical models. So our marketing strategy is we believe is essential for creating a therapeutic window.

Sean A. McCarthy: This tumor localization leads to the improvement or creation of a therapeutic window. For the EGFR-CD3 antigen pair, it has been shown previously that the unmarked bispecific is highly toxic in preclinical models. So our masking strategy is, we believe, essential for creating a therapeutic window.

Sean A. McCarthy: In terms of the toxicities we're looking to mitigate, EGFR antibodies are well known to cause rash and gastrointestinal side effects. And so we've been specifically looking out for our masking strategy to really limit serious EGFR toxicities, particularly grade 3 and above. With regard to CD3, our masking strategy is, of course, designed to limit CRS and ICAM.

Sean A. McCarthy: In terms of the toxicities were looking to mitigate egfr antibodies are well known to cause rash and gastrointestinal side effects.

Sean: So we've been specifically looking at looking at for our marketing strategy to really limit Sirius Egfr toxicities, particularly grade three and above with regard to CD three our marketing strategy is of course designed to limit Crs and icons.

Speaker Change: Before handing over to why wait let me review.

Sean A. McCarthy: Before handing over to Wayne, let me review the high-level goals and achievements to date for our Phase 1 study of CX904. Given the really high potency of T cell engagement and the widespread expression of EGFR, goal number one for this study has been to evaluate the safety of 904, and we've made excellent progress, as you will see from Wayne's presentation. We explored non-STEP and STEP dosing.

Sean A. McCarthy: The high level goals and achievements to date for.

Sean A. McCarthy: For our phase one study of CX 904.

Speaker Change: Given the really high potency of T cell engages and the widespread expression of Egfr goal number one for this study has been to evaluate the safety of 904, and we've made excellent progress as Youll see from Wayne's presentation.

Sean: We've explored non step and step dosing, we were very pleased to see very limited Crs with non step dosing, we believe because of successful CD three market.

Sean A. McCarthy: We were very pleased to see very limited CRS with non-STEP dosing. We believe this is because of successful CD3 masking, and in step dosing cohorts, rather remarkably, we've seen no CRS at all. We've also seen no evidence of ICANNs at any dose level or schedule.

Sean: And didn't step dosing cohorts, rather remarkably we've seen no crs at all.

Sean: We've also seen no evidence of <unk> at any dose level four schedule.

Sean: Furthermore, while we have seen some egfr toxicities. These have been manageable and have not limited us in achieving therapeutically active doses.

Sean A. McCarthy: Furthermore, while we have seen some EGFR toxicities, these have been manageable and have not limited us in achieving therapeutically active doses. Again, this shows the success, we believe, of our eGFR masking strategy, and this success of eGFR masking is consistent with our prior published work that I mentioned earlier. Goal number two of our phase one study has, of course, been to look for initial signs of anti-tumor activity. As we've said in recent months, any evidence of tumor stabilization or tumor shrinkage in this first-in-man study would be very encouraging.

Sean: Again. This shows the success, we believe of our Egfr marketing strategy and the success of Egfr masking is consistent with our prior published work that I mentioned earlier.

Sean: Goal number two of our phase one study has of course been to look for initial signs of antitumor activity.

Sean A. McCarthy: As we've said in recent months any evidence of tumor stabilization or tumor shrinkage. In this first demand study will be very encouraging I want to emphasize that the patient population we've enrolled.

Sean A. McCarthy: I want to emphasize that the patient population we've enrolled to date in this Phase I study is heavily pretreated with a range of tumor types and is unselected for EGFR. All that said, we're delighted to announce today very encouraging early signs of anticancer activity for 904, including confirmed resistance responses in pancreatic cancer, a very difficult to treat tumor type that is not typically responsive to eGFR inhibition or, for that matter, to immunotherapy.

Sean: Date in this phase one study is heavily pre treated and has a range of tumor types and is unselected for egfr.

Sean A. McCarthy: All that said, we're delighted to announce today very encouraging early signs of anticancer activity for 904, including confirmed resist responses in pancreatic cancer, a very difficult to treat tumor type that is not typically a responsive to egfr inhibition or for that matter to immunotherapy.

Sean: Moreover, our initial assessments to pharmacodynamics are supportive of the mechanism of action of CX 904, as a mosque T cell engagement, providing crucial platform proof of concept with read through we believe to the many other programs were working on <unk>.

Sean A. McCarthy: Moreover, our initial assessments of pharmacodynamics are supportive of the mechanism of action of CX904 as a mass T-cell engager, providing crucial platform proof of concept with read-through, we believe, to the many other programs we're working on at CytomX.

Sean: Importantly, this phase one study is ongoing we're continuing to dose escalate and enroll multiple tumor types, but our next goal is to determine the recommended phase II dose and to define plans for phase one expansions.

Sean A. McCarthy: Importantly, this Phase 1 study is ongoing. We're continuing to dose-escalate and enroll multiple tumor types, and our next goal is to determine the recommended Phase 2 dose and to define plans for Phase 1b expansion. We see the data that we're sharing today as a very promising initial step in the development of CX904, and this work positions CytomX at the forefront of the T cell engager field. Now, I will hand over to Wayne to review the data in some detail.

Sean: We see the data that we're sharing today as a very promising initial step in the development of CX 904, and this work positions <unk> at the forefront of the T cell engage a field now let me hand over to Wayne to review the data in some detail.

Wayne Chu: Thanks, Shawn and thanks, everyone for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study.

Wayne Chu: Thanks, Sean, and thanks, everyone, for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study. This slide summarizes the dose escalation scheme, key eligibility criteria, and study objectives. Patients with tumors with no EGFR expression were enrolled. However, patients were not selected based on EGFR expression. Dose escalation was initiated using a non-step dosing schedule in which CX904 was dosed once every two weeks. Doses starting from 7 micrograms through 6 milligrams were tested.

Wayne Chu: This slide summarizes the dose escalation scheme key eligibility criteria and study objectives.

Wayne Chu: Patients with tumors with known Egfr expression, where enroll however patients were not selected based on Egfr expression.

Sean: Dose escalation was initiated using a non step dosing schedule and which CX 904 was dosed once every two weeks.

Sean: Doses, starting from seven micrograms through six milligrams were tested.

Wayne Chu: As we will discuss in the subsequent slides, dose escalation of CX904 continued using a step-dosing schedule with an initial target dose of 5 millibars. Various step-dosing schedules were tested, after which the target dose was administered every two weeks. The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose. And, as Sean mentioned, dose escalation continues with the current enrollment testing the 15 milligram target dose.

Sean: We will discuss in the subsequent slides dose escalation of CX 904 continued using a step dosing schedule with an initial target dose of five milligrams.

Wayne Chu: Various step dosing schedules were tested after which the target dose was administered every two weeks.

Sean: The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose.

Wayne Chu: And as Sean mentioned dose escalation continues with the current enrollment testing the 15 milligram target dose.

Sean: Selected baseline characteristics for enrolled patients are shown in this slide.

Wayne Chu: Selected baseline characteristics for enrolled patients are shown in this slide. The majority of patients enrolled in non-step dosing escalation cohorts were those with microsatellite-stable or MSS colorectal cancer, which I will call Perm CRC from here on out, which has been demonstrated to be unresponsive to immune therapies such as checkpoint inhibitors. With step-dose escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity, as well as other tumor types with known EGFR expression.

Sean: The majority of patients enrolled in non stop dosing escalation cohorts, where those with microsatellite stable or MSS colorectal cancer, which our perm.

Sean: <unk> CRC from Hereon out, which has been demonstrated to be unresponsive immune therapies, such as checkpoint inhibitors.

Wayne Chu: With step dosing with step dosing escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity as well as other tumor types with known Egfr expression.

Wayne Chu: As is typical for a Phase I first-in-human dose escalation study, patients had advanced late-line disease. Enrolled patients received a median of four prior cancer therapies, many were refractory to their last prior therapy, and a considerable proportion received prior EGFR and or PD-1 and PD-L1-directed therapy. Early clinical pharmacokinetic data from the non-step dosing schedule was consistent with the CX904 ProBody T-Cell Engager design. The graph on the left shows that total CX904 exposure increases linearly with increasing dose, indicating no apparent change in dose-dependent clearance or evidence of target-mediated drug disposition.

Sean: As is typical for a phase one first in human dose escalation study patients had advanced late line disease enrolled patients received a median of four prior cancer therapies. Many were refractory to their last prior therapy and a considerable proportion received prior egfr and our PD, one and <unk>.

Sean: PD lone directed therapy.

Sean: Yeah.

Sean: Early clinical pharmacokinetic data from the non step dosing schedule was consistent with the CX 904 pro body T cell engagement design. The graph on the left shows that total CX 904 exposure increases linearly with increasing dose, indicating no apparent change in dose dependent clearance or evidence of tar.

Sean: <unk> mediated drug disposition.

Wayne Chu: The graph on the right shows the cycle 1 PK profile of CX904 at the 3 milligram dose level. The three curves show circulating analyte concentrations of intact, or masked, CD3, intact EGFR, and total probody. Notably, the three curves are essentially superimposable, indicating that CX904 exists in circulation in predominantly intact, or masked, form. Preliminary estimates of CX904 half-life are between 2.8 and 5.3 days.

Sean: The graph on the right shows the cycle, one PK profile of CX 904 at the three milligram dose level. The three curves showed circulating analyte concentrations of intact or mask CD three intact, Egfr and total pro body, notably the three curves are essentially.

Wayne Chu: Superimposed <unk>, indicating that CX 904 exists in circulation and predominantly intact or matched form.

Sean: Preliminary estimates of CX 904 half life are between two 8% and five three days.

Sean: This slide summarizes treatment related adverse events observed with CX 904 into non step dosing schedule. It.

Wayne Chu: This slide summarizes treatment-related adverse events observed with CX904 in the non-step dosing schedule. It is important to mention that during the CX904 escalation, no corticosteroids or other prophylactic medication was administered for systemic toxicity, such as CRS and IQ. The safety and tolerability data shown here with non-step dosing therefore reflect the ability of the masking to mitigate CRS and IQ. Considering that, the virtual absence of CRS and ICANN is quite striking.

Sean: It is important to mention that during the CX 904 escalation no corticosteroids or other prophylactic medication was administered for systemic toxicities, such as Crs and <unk>.

Sean: The safety and Tolerability data shown here with non step dosing, therefore reflect the ability of the masking to mitigate Crs and ICANN.

Sean: With that the virtual absence of Crs and I cant is quite striking.

Wayne Chu: Through the 3 mg dose level, no CRS or ICANs of any grade were observed. Even at the 6 mg dose level, where two patients had dose-limiting toxicity of grade 3 tinnitinovitis and grade 3 rash, no patients experienced icons of any grade, and only grade 1 CRS, characterized by transient fever without any other signs or symptoms associated with CRS, was observed. Low-grade musculoskeletal adverse events, such as arthralgia and arthritis, were observed in addition to one grade three tenosynovitis at the six milligram dose level.

Sean: The three milligram dose level, no crs or I can of any grade were observed.

Sean: Even at the six milligram dose level, where two patients had dose limiting toxicity of great <unk> tennis, synovitis and grade three rash no patients experienced I can't have any grade and only grade one crs characterized by transient fever without any other signs or symptoms associated with Crs was.

Wayne Chu: Observed.

Sean: Low grade musculoskeletal adverse events, such as our <unk> and arthritis were observed in addition to the one great three tenets synovitis at the 60 milligram dose level.

Wayne Chu: Musculoskeletal events overall appear to be associated with a dose-dependent increase in circulating IL-6, as shown in the graph. This is in direct contrast with CRS, where the association with circulating IL-6 levels was much less evident. Similarly, except for the grade 3 rash observed at the 6 milligram dose level, only grade 1 rash was observed. Overall, the data presented here quite convincingly demonstrate the benefit of masking on effectively eliminating CRS and ICANNs, which constitute dose-limiting toxicities with high T cell engagement.

Sean: Muscular skeletal events overall appear to be associated with each dose dependent increase in circulating IL six as shown in the graph.

Sean: This is in direct contrast with Crs.

Sean: The association with circulating IL six levels with much less evident.

Sean: Similarly, except for the a grade three rash observed at the six milligram dose level only grade one rash was observed.

Sean: Overall, the data presented here quite convincingly demonstrate the benefit of masking on effectively eliminating <unk> and ICANN, which constitute dose limiting toxicity with many T cell engagements.

Sean: Based on the observations during dose escalation on the non step dosing schedule, which demonstrated that Crs and <unk> are effectively mitigated by the masking of CX 904 step dosing schedules and total listener prophylaxis, where you'd specifically to mitigate emerging muscular skeletal adverse events.

Wayne Chu: Based on the observations during dose escalation on the non-STEP dosing schedule, which demonstrated that CRS and ICANs are effectively mitigated by the masking of CX904, STEP dosing schedules and tocilizumab prophylaxis were used specifically to mitigate emerging musculoskeletal adverse events, maintain a broad therapeutic index, and allow continuation of escalation to higher and potentially more efficacious target dose These measures enabled escalation to higher CX904 target doses while continuing to maintain an acceptable safety and tolerability profile. Impressively, no CRS or ICAN of any grade was observed.

Sean: We maintain a broad therapeutic index and allow continuation of escalation to higher and potentially more efficacious target doses.

Sean: These measures enabled escalation to higher CX nine of our target doses, while continuing to maintain an acceptable safety and tolerability profile impress.

Sean: Impressively, no crs or I can sum any grade was observed.

Wayne Chu: Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX904 target doses, no related grade 3 rashes were reported, and no treatment-related adverse events resulted in CX904 treatment discontinuation. Overall, the safety profile of CX904 continues to be favorable and importantly enables CX904 administration and management of adverse events in an outpatient setting. In this regard, per protocol, no mandatory hospitalization is required for monitoring at clear dose levels, and the safety profile observed to date has not necessitated a change to this practice.

Sean: Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX 904 target doses no related grade three rash its were reported and no treatment related adverse events resulted in CX 904 treatment discontinuation.

Sean: Overall, the safety profile of CX 904 continues to be favorable and importantly enables CX 904 administration and management of adverse events in an outpatient setting and <unk>.

Sean: This regard per protocol no mandatory hospitalization is required for monitoring a clearer dose levels and the safety profile observed to date has not necessitated a change to this practice.

Sean: In the context of a favorable safety profile, we observed compelling signs of CX 904, anti tumor activity highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma.

Wayne Chu: In the context of a favorable safety profile, we observed compelling signs of CX904 anti-tumor activity, highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma. The responses observed with CS904 are highly encouraging given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely poor with current available therapy. Shown here is the waterfall plot of six efficacy-evaluable patients treated across a range of target doses on both non-STEP and STEP dosing schedules. Confirmed partial responses per RESIST 1.1 criteria were observed in two of the six patients.

Wayne Chu: One was treated with six milligrams on a non-step dosing schedule and had an 83% reduction in measurable tumor burden, and a second patient was treated on a step dosing schedule with a target dose of five milligrams and had a 51% reduction in tumor burden. Furthermore, of note, all six patients have disease control. Of the six patients, two remain on study treatment, and we will now discuss these patients in greater detail. The first case describes a confirmed partial response in a 49-year-old patient with metastatic pancreatic adenocarcinoma.

Sean: The responses observed with <unk> are highly encouraging given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely poor with current available therapies.

Sean: Here is the waterfall plot of six efficacy evaluable patients treated across a range of target doses on both non step in step dosing schedules.

Wayne Chu: Confirmed partial responses per resist one one criteria were observed in two of the six patients one was treated with six milligrams on a non stop dosing schedule and had an 83% reduction in measurable tumor burden and a second patient was treated on a step dosing schedule with a target dose of five milligrams and had a 51.

Wayne Chu: 1% reduction in tumor burden.

Wayne Chu: Furthermore of note all six patients.

Wayne Chu: Had disease control.

Sean: Of the six patients to remain on study treatment and we will now discuss these patients in greater detail.

Wayne Chu: The first case describes a confirmed partial response and a 49 year old patient with metastatic pancreatic adenocarcinoma prior therapies, including surgery radiation therapy, and three lines of prior chemotherapy to.

Wayne Chu: Prior therapies included surgery, radiation therapy, and three lines of prior chemotherapy. The patient received CX904 on a step-dosing schedule with 1.5 milligrams administered on day one, and the target dose of 5 milligrams administered one week later and then two weeks thereafter every two weeks thereafter. The patient did not experience cytokine relief syndrome or ICANS. The patient experienced grade three related arthralgia, but this resulted in grade one after a one cycle delay in the administration of corticosteroids.

Sean: The patient receives CX 904 on a step dosing schedule with one five milligrams administered on day, one and the target dose of five milligrams administered one week later and then two weeks thereafter every two weeks thereafter.

Sean: The patient did not experienced cytokine release syndrome or <unk>, the patient experienced grade three related arthralgia, but this result, the great. One after one cycle delay and administration of political steroids at.

Sean: As shown in the CET scan images the patient achieved a partial response.

Sean: With deeper reduction in tumor burden observed at the confirmatory scan and as I mentioned and this patient remains on CX 904 treatment, having received over three months of treatment to date.

Sean: This next case illustrates durable stable disease with CX 904, and a 59 year old patient with metastatic pancreatic adenocarcinoma, who had received three prior lines of systemic chemotherapy.

Wayne Chu: As shown in the CT scan images, the patient achieved a partial response, with a deeper reduction in tumor burden observed at the confirmatory CT scan. And as I mentioned, this patient remains on CX904 treatment, having received over three months of treatment to date. This next case illustrates durable, stable disease with CX904 in a 59-year-old patient with metastatic pancreatic adenocarcinoma who had received three prior lines of systemic chemotherapy. The patient received CX904 on a step-dosing schedule with 1.5 milligrams administered on day 1, 5 milligrams on day 8, and 10 milligrams on day 15 every two weeks thereafter. The patient tolerated CX904 treatment well, with no CRS, ICANs, or musculoskeletal events and only grade one papulopustular rash, which resolves with topical treatment.

Wayne Chu: The patient received <unk> four on a step dosing schedule with one five milligrams administered on day, one five milligrams on day, eight and 10 milligrams on day 15 every two weeks thereafter.

Sean: Patient tolerated CX 904 treatment well with notes Crs I can or muscular skeletal events.

Sean: And only great one popular plus your rash, which resolved with topical treatment.

Wayne Chu: The patient was able to maintain stable disease with no evidence of measurable tumor growth, and additional information supporting continued clinical benefit included a greater than 50% reduction in serum CA-19 levels and overall improvement of performance status from baseline. This patient remains on CX904 treatment, having received over three and a half months of treatment to date. Preliminary translational data indicate T-cell pharmacodynamic activity that is consistent with the mechanism of action of CX904 in pancreatic adenocarcinoma.

Sean: The patient was able to maintain stable disease with no evidence of measurable tumor growth and additional information supporting continued clinical benefit included a greater than 50% reduction in serum CA 19 levels and overall improvement of performance status from baseline.

Sean: This patient remains on CX 904 treatment, having received over three five months of treatment to date.

Sean: Preliminary translational data indicates T cell pharmacodynamic activity that is consistent with the mechanism of action of <unk> in pancreatic adenocarcinoma.

Wayne Chu: The figure on the left is an immunofluorescent image from a biopsy obtained prior to CX904 treatment in a patient with pancreatic cancer who achieved a deep partial response. The colors indicate T cell markers in red, dark blue, and magenta, and cancer cells in light blue.

Sean: Figure on the left is an immuno fluorescence image from a biopsy obtained prior to CX 904 treatment.

Sean: Patients with pancreatic cancer, who achieved a deep partial response, the colors indicate T cell markers and red dark blue and magenta and cancer cells in light Blue and as you can see the pretreatment biopsy showed a high level of CD positive T cells within the tumor microenvironment, indicating their contribution to T cell engagement anti tumor activity.

Wayne Chu: And as you can see, the pre-treatment biopsy showed a high level of CD8 positive T cells within the tumor microenvironment, indicating their contribution to T cell engaged anti-tumor activity. The figure on the right shows the reduction of peripheral CD8 positive T cells as it relates to the resist 1.1 response. Both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CD8 positive T cells following CX904 treatment, consistent with the trafficking of T cells from the periphery to tumor sites as a mechanism of action of T cell engagement.

Sean: <unk>.

Sean: The figure on the right shows the reduction of peripheral CDA positive T cells as it relates to resist one one response, both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CDA positive T cells. Following CX 904 treatment consistent with the trafficking of T cells from the periphery to <unk>.

Wayne Chu: <unk> as a mechanism of action of Keystone indicators.

Sean: Taking a step back from the early but compelling activity of CX 904 in patients with pancreatic adenocarcinoma shown here is the waterfall plot for efficacy evaluable patients treated with <unk> for our target doses greater than or equal to <unk> 75 milligrams.

Wayne Chu: Taking a step back from the early but compelling activity of CX904 in patients with pancreatic adenocarcinoma, shown here is the waterfall plot for efficacy-evaluable patients treated with CX904 at target doses greater than or equal to 0.75 milligrams. While no objective responses were observed in patients with other tumor types, reductions in measurable disease burden were observed in a total of eight patients, including Reductions in measurable disease burden were also observed in patients with CRC, esophageal carcinoma, and non-small cell lung cancer. We believe that the early signals of CX904 activity in pancreatic cancer are compelling and that currently tested target doses are efficacious.

Sean: While no objective responses were observed in patients with other tumor types reductions and measurable disease burden were observed in the total of eight patients, including the two pancreatic cancer patients with partial responses reductions and measurable disease burden were also observed in patients with CRC esophageal carcinoma and non small.

Sean: Cell lung cancer.

Wayne Chu: We believe that early signals of CX 904 activity in pancreatic cancer are compelling and that currently tested target doses are efficacious.

Wayne Chu: As a result, study enrollment moving forward will focus on patients with other EGFR-positive tumor types, including lung cancer, upper GI cancers, and head and neck cancers. This slide summarizes the time-on-study treatment for patients treated with CX904, again highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit from ongoing CX904 treatment. Importantly, while CX904 has had minimal clinical activity to date in patients with CRC, it retains its pharmacodynamic activity, as illustrated in this slide, which are immunofluorescent images of biopsies taken from a patient with MSF-CRC at baseline and while on CX904 treatment.

Wayne Chu: As a result study enrollment moving forward in addition to continuing to enroll patients with pancreatic cancer will focus on patients with other egfr positive tumor types, including lung cancer upper Gi cancers in head and neck cancers.

Sean: This slide summarizes the time on study treatment for patients treated with CX 904, again, highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit with ongoing CX 904 treatment.

Sean: Importantly, while <unk> has had minimal clinical activity to date in patients with CRC.

Sean: 904 retained its pharmacodynamic activity as illustrated in this slide which are immuno fluorescent images of biopsies taken from a patient with MSS CRC at baseline and while on CX 904 treatment as.

Wayne Chu: As you can clearly see at baseline, the tumor's tumor is notable for the almost complete absence of CD8 positive T cells within the tumor. In contrast, the on-treatment biopsy showed a substantial increase in the number of CD8 positive T cells within the tumor.

Wayne Chu: As you can clearly see at baseline the tumors tumor is notable for the almost complete absence of <unk>.

Wayne Chu: <unk> positive T cells within the tumor.

Sean: In contrast, the on treatment biopsies showed a substantial increase in the number of CDA positive T cells within the tumor.

Wayne Chu: This observation is a clear demonstration of the CX904 mechanism of action and demonstrates potential combination strategies for the treatment of CRC. In summary, we are very encouraged by this early clinical data of CX904 in the ongoing phase 1 dose escalation. CX904 has a favorable safety profile, which, given the broad expression of EGFR in normal tissues in addition to cancers, is indicative of the ability of masking to maintain a meaningful therapeutic index. Second, CX904 has promising early efficacy and pharmacodynamic activity, highlighted by the confirmed posture responses in patients with metastatic pancreatic adenocarcinoma and early demonstration of its mechanism of action, including in colore

Sean: Observation is a clear demonstration of the CX 904 mechanism of action and demonstrates potential combinations strategies for the treatment of CRC.

Wayne Chu: In summary, we are very encouraged by this early clinical data on CX 904, and the ongoing phase one dose escalation.

Sean: <unk> has a favorable safety profile, which given the broad expression of Egfr in normal tissues. And addition to cancers is indicative of the ability of masking to maintain a meaningful therapeutic index.

Sean: CX 904 has promising early efficacy and pharmacodynamic activity highlighted by the confirmed partial responses in patients with metastatic pancreatic adenocarcinoma and early demonstration of CX 904 mechanism of action, including <unk>.

Wayne Chu: Colorectal cancer.

Wayne Chu: The clinical and translational observations have been extremely valuable in demonstrating not only the early clinical activity of CX904, but also provide clear direction to plans to ultimately determine the recommended phase 2 dose. This includes continued enrollment in pancreatic cancer and enrollment in other EGFR-positive tumor types that are also more responsive to immune therapies based on prior clinical experience. Together, these data will inform future development of CX904, which will include consideration of combination strategies. And with that, I will now turn it back to Sean for concluding remarks. Great

Sean: The clinical and translational observations have been extremely valuable and demonstrating not only get early clinical activity of <unk>, one, but also provide clear direction to plans to ultimately determine the recommended phase II dose and this includes continued enrollment in pancreatic cancer and enrollment and other egfr positive tumor types that are also more.

Sean: Sponsors to immune therapies based on prior clinical experience.

Sean: Together these data will inform future development of CX 904, which include consideration of combination strategies and with that I will now turn it back to Sean for concluding remarks.

Sean: Great. Thanks Wayne.

Sean A. McCarthy: Thanks, Wayne. So, staying with CS904 for a moment, we're excited by our progress to date in developing this very novel drug candidate. EGFR is such a high potential target with expression in many tumor types, and we're just at the beginning of learning what CX904 can do for patients. We clearly have a drug candidate with confirmed monotherapy activity, and we're redoubling our efforts to generate data in additional tumor types as we more broadly explore 9.04.

Sean: So staying with <unk> 94 for a moment, we're excited by our progress to date developing this very novel drug candidate <unk>.

Sean: <unk> is such a high potential target with expression on many tumor types and we're just at the beginning of learning what CX 904 can do for patients.

Sean: We clearly have a drug candidate with confirmed monotherapy activity, but we're redoubling our efforts to generate data in additional tumor types as we more broadly explore in Idaho for I would say, it's also unlocks potential strategies for future combinations as Wayne mentioned.

Sean A. McCarthy: Our data also unlocks potential strategies for future combinations, as Wayne mentioned. Focusing for a moment on pancreatic cancer, this is one of the greatest areas of unmet need in oncology today, and it's notoriously difficult to treat. Second-line response rates are in the single digits, and PFS and overall survival are just a matter of months. To reiterate the importance of our data shared today, pancreatic cancer does not respond to either anti-EGFR antibodies or to immunotherapy alone.

Sean: Focusing for a moment on pancreatic cancer. This is one of the greatest areas of unmet need in oncology today, and it's notoriously difficult to treat.

Sean: Second line response rates are in the single digits.

Sean: And overall survival is just a matter of months.

Sean: To reiterate the importance of our data shared today pancreatic cancer does not respond to either anti egfr antibodies or to immunotherapy alone.

Sean A. McCarthy: What we have shown today is that when we combine these two powerful strategies in bi-specific form, enabled by our pro-body masking technology, we can elicit meaningful responses in late-stage pancreatic cancer patients. CS904 brings these two mechanisms together into an integrated and unique pharmacology that can impact this very difficult-to-treat disease, showing how masked pro-body T-cell engagers can be a new frontier in the These results are the embodiment of exactly what CX904 was designed to do, and we plan to aggressively pursue this signal for the benefit of people afflicted with this devastating tumor type.

Sean: What we have shown today is that when we combine these two powerful strategies and by specific form.

Sean: Enabled by our priority masking technology, we can elicit meaningful responses in late stage pancreatic cancer patients.

Sean A. McCarthy: 94 brings these two mechanisms together into an integrated and unique pharmacology that could impact this very difficult to treat disease.

Sean A. McCarthy: How mast <unk> T cell engages can be a new frontier in the war on cancer.

Sean: These results are the embodiment of exactly what CX 904 was designed to do and we plan to aggressively pursue this signal for the better for the benefit of people afflicted with this devastating tumor type.

Sean A. McCarthy: Now zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at <unk>, we see the data. We're sharing today are 94 is a promising initial step in developing this asset and also our T cell engaging portfolio.

Sean A. McCarthy: Now, zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at CytomX. We see the data we're sharing today on 904 as a promising initial step in developing this asset and also our T-Cell Engager portfolio overall. T-Cell Engagers are starting to break through in solid cancers, and it's exciting to be playing our part here at CytomX in this highly promising field, not only with 904, but also the many T-Cell Engager programs we're advancing through preclinical discovery and development. And we look forward to providing an additional CS904 update later this year.

Sean: <unk>.

Sean A. McCarthy: T cell engages are starting to break through in solid cancers, and it's exciting to be playing our part.

Sean A. McCarthy: Cytogenetics in this highly promising field not only with <unk>, but also the many T cell engaging programs, we're advancing through preclinical discovery and development and we look forward to providing an additional CX 904 updates later this year.

Sean A. McCarthy: Of course, today's update has been very 904 focused, but before I wrap up, I'd like to remind everyone to also keep our other programs in mind. We're making a lot of progress on multiple fronts. CX-2051 and CX-801 are wholly-owned assets, and we anticipate Phase Ia data for both in 2025.

Sean A. McCarthy: Of course todays update has been very 904 focus, but before I wrap up I'd like to remind everyone to also keep our other programs in mind we're.

Sean: We're making a lot of progress on multiple fronts <unk> five one and CX 801, our wholly owned assets and we anticipate phase one data for both in 2025 were already in our second phase one cohort with 2051 amongst anti outcome ADC and clinical initiation for CX 800.

Sean A. McCarthy: We're already in our second Phase I cohort with 2051, a masked anti-Epcan ADC, and clinical initiation for CX-801, a masked interferon, is imminent. I'd like to close by thanking everyone involved in this work for their commitment to our vision. The CytomX team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer, and it's truly a privilege to work with such a talented group.

Sean: One must interferon is imminent.

Speaker Change: I'd like to close by thanking everyone involved in this work for their commitment to our vision. The <unk> team is intensely focused on delivering an innovative pipeline for the benefit for people living with cancer and it is truly a privilege to work with such a talented team I also want to sincerely. Thank the patients who join our studies their families.

Sean A. McCarthy: I also want to sincerely thank the patients who join our studies, their families, and our investigators. And with that, Operator, let's go ahead and open up the call for questions. Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.

Speaker Change: And our investigators and with that operator, let's go ahead and open up the call for questions.

Speaker Change: Thank you and as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced so which are a question. Please press star one again.

Operator: Please stand by while we compile the Q&A. And for our first question, it comes from the line of Peter Lawson from Barclays. Please go ahead. Thank you so much.

Speaker Change: Please stand by we'll be compile the Q&A roster.

Speaker Change: And for our first question comes from the line of Peter Lawson from Barclays. Please go ahead.

Peter Richard Lawson: Great. Thank you so much thanks for sharing the data.

Peter Richard Lawson: Thanks for sharing the data. Really exciting. The masking benefit you've seen, do you think that it can also extend to other T cell engages and then? Sponsors you've seen so far?

Peter Richard Lawson: Great exciting.

Peter Richard Lawson: The market benefit you've seen do you think that can they also extend to other T cell engages and then the responses <unk> seen so far.

Peter Richard Lawson: Do you think at some special about pancreatic cancer do you think you can.

Peter Richard Lawson: Deep responses and other tissues as well.

Speaker Change: Yes, Hi, Peter Great great questions. Thanks.

Sean A. McCarthy: Do you think there's something special about pancreatic cancer, or do you think... get deeper responses in other, Yeah. Hi Peter. Great, great questions. Thanks. Regarding the extension and the read-through to other programs, we're obviously very optimistic that that will be the case. You've got to start somewhere, and 904, I think, is a very strong start for us. We've learned a lot with this one in the clinic, and as we've mentioned both internally and with our partners, we're doing a lot of work on T-cell engagers. We have multiple programs.

Sean A. McCarthy: Regarding the extension and the read through to other programs. So we're obviously very optimistic that that will be the case.

Peter: You've got to start somewhere and 904 I think is a very strong start for us.

Speaker Change: We've learned a lot with this one in the clinic and as we've mentioned.

Peter Richard Lawson: Both internally.

Sean A. McCarthy: And with our with our partners, where we're doing a lot of work and see some engagements. We've got multiple programs. In fact, the majority of our our partnered work is in T cell <unk>. So we would expect to make substantial additional progress here over the next few years.

Sean A. McCarthy: In fact, the majority of our partnered work is in T-cell engagers, so we would expect to make substantial additional progress here over the next few years. In terms of pancreatic cancer, I think it's a great question. It's been interesting to see.

Peter Richard Lawson: In terms of pancreatic I think it's a great question.

Peter Richard Lawson: It's been interesting to see.

Peter Richard Lawson: Yes.

Sean A. McCarthy: We've done a lot of thinking about this, obviously, and pancreatic is typically thought of as an immunologic cold tumor or an immunologic desert, if you like, but actually, evidence is beginning to mount suggesting that that might not be the case. If you look at the Roche BioNTech vaccine data, most recently updated at ACR, it's really interesting. It suggests that there are neoantigens in pancreatic cancer, that there is some immunologic microenvironment, and it looks like with this combination of...well, there's also EGFR, of course, there, but no one has been able to break through with an anti-EGFR-directed therapy, so we think there could be something very unique about EGFR and CD3 in this particular tumor type, but it absolutely does not indicate As Wayne mentioned, the... The colorectal data is interesting. They're all MSS patients that we're showing today. That's another cold tumor.

Peter Richard Lawson: We've done a lot of thinking about this obviously in <unk>.

Sean A. McCarthy: Pancreatic is typically thought of as.

Peter Richard Lawson: In immunology cold tumor or.

Peter Richard Lawson: The logic desert, if you like but actually evidence is beginning to.

Peter Richard Lawson: <unk>, suggesting that that might not be the case, if you look at the Roche <unk>.

Sean A. McCarthy: Vaccine data most recently updated at ACR.

Sean A. McCarthy: It's really interesting that suggests that there are.

Peter Richard Lawson: <unk>.

Peter Richard Lawson: Neo androgens in pancreatic cancer.

Sean A. McCarthy: Some immunologic microenvironment it.

Peter Richard Lawson: It looks like with this combination of each well and Theres also egfr of course there.

Peter Richard Lawson: But no one's been able to breakthrough with an anti egfr directed therapies. So we think that could be something very unique about egfr CD three in this particular tumor type.

Peter Richard Lawson: But it does not indicate the others.

Peter Richard Lawson: Would not respond to 904, we're still very early in this study as Wayne mentioned the.

Peter Richard Lawson: The colorectal data is interesting.

Sean A. McCarthy: Not a lot of progress has been made with T-cell gauges yet in CRC, so we would be looking to combination strategies there. As far as the other tumor types are concerned, it's just very, very early days. For example, I'd cite lung, where we have two patients in the dose escalation study to date. One of those was treated at a very low dose, so probably not relevant. We just haven't done the experiment yet, so we're going to keep rolling across multiple tumor types in Phase 1a as we continue to pursue both the pancreatic signal and define the activity of the drug across, hopefully, multiple tumor types over time.

Peter Richard Lawson: They're all MSS patients that we're showing today.

Peter Richard Lawson: That's another cold tumor.

Peter Richard Lawson: But a lot of progress has been made with T cell engages yet.

Sean A. McCarthy: CRC, so we would be looking to combination strategies there as far as the other tumor types are concerned. It's just very very early days for example, I would cite lung where we have two patients in the dose escalation study to date one of those was treated at a very low dose. So probably don't relevant we've really already there just havent done the experiment yet so we're going to keep enrolling across multiple tiers.

Peter Richard Lawson: Sites in phase Iia as we.

Sean A. McCarthy: Continue to pursue both the pancreatic signal and.

Peter Richard Lawson: <unk> defined the activity of the drug across hopefully multiple tumor types over time.

Speaker Change: Great. Thank you and then.

Sean A. McCarthy: And then the depth of the responses, is that related to EGFR expression, or is it tumor micro... So one thing we have not shown in this presentation, but we continue to evaluate, is the level of eGFR expression as assessed by an immunohistochemistry assay. And we've been doing this on a retrospective basis for all the patients that have enrolled. To date, based on our early data with eGFR using this IHC assay, we have not seen a clear association between eGFR expression and the depth of the response.

Sean A. McCarthy: The depth of the responses.

Peter Richard Lawson: <unk>.

Peter Richard Lawson: Correlated with Egfr expression or is it tumor micro environment.

Peter Richard Lawson: So one thing we have not shown was shown in this presentation, but we continue to evaluate as the level of Egfr expression as assessed by immunohistochemistry assay and we've been doing this on a retrospective basis.

Peter Richard Lawson: For all the patients that have enrolled to date based on our early data with Egfr by this IAC assay, we have not seen a clear association between Egfr expression and the and the depth of the response and just as an example.

Sean A. McCarthy: And just as an example, the two patients with pancreatic cancer who had a confirmed partial response; one patient had a moderately high level of eGFR expression by IHC, but the other patient had a very low level of eGFR expression.

Peter Richard Lawson: The two patients in pancreatic cancer.

Peter Richard Lawson: Had the confirmed partial response, one patient had a moderately high level of Egfr expression by IAC, but then the but the other patient had a very low level of Egfr expression and it's actually the patient who had the 83% reduction in measurable tumor burden that has a low level of egfr expression.

Wayne Chu: And it's actually the patient who had the 83% reduction in measurable tumor burden that had the low level of eGFR expression. I think more work needs to be done there, but Peter, a lot of it depends on the assay itself, so we'll continue to look at that relationship. I'll get back into the queue.

Peter Richard Lawson: Interesting.

Peter Richard Lawson: More and more word yes, more work to be done there, but a.

Peter Richard Lawson: Peter a lot of it depends also on the assay itself. So we'll continue to look at that relationship.

Speaker Change: Great I'll get back.

Speaker Change: Thank you so much.

Speaker Change: Thank you.

Operator: Thank you so much. And for the next question, it comes from the line of Roger Song from Jeffreys. Please go ahead. Great, congratulations on the data, and thank you for taking our question. A few questions from us.

Roger Song: And for our next question comes from the line of Roger song from Jefferies. Please go ahead.

Speaker Change: Great.

Roger Song: For the data and thank you for taking my question.

Roger Song: The first one is related to the dose relationship. Since efficacy or anti-tumor activity is not clearly correlated with the dose level. My question is, how do you think about the balance between the efficacy and, you know, CRS, ICANN, more CD3 or EGFR-related vaccine? How confident are you that you can keep dosing higher? Yeah, thanks, Roger. Let me kick that one off.

Roger Song: A few questions from us the first one is related to that those relationship.

Speaker Change: Since the efficacy or antitumor.

Roger Song: Activity is not clearly, Colorado with the dose level. My question is how do you think about as you dose higher.

Roger Song: Beyond <unk> and now you add the fifth seeing how do you think about the balance between the Africa and Crs.

Speaker Change: I can more easily all egfr, Romania that.

Speaker Change: Yes.

Speaker Change: <unk> profile.

Speaker Change: Sure.

Speaker Change: How confident you are you can keep dosing higher thank you.

Speaker Change: Yes, Thanks, Roger let me kick that one off.

Sean A. McCarthy: You know, I say that there is a dose response in that the responses that we're seeing, the confirmed resistance responses, you know, we've seen at five and six milligrams. But remember that we began this dose escalation at seven micrograms. So, you know, the range of doses where we're seeing activity is actually really consistent with our predictions from modeling of where the biologically effective range would be. So we think we're in the zone.

Sean A. McCarthy: Yes.

Roger Song: There is a dose response in that.

Sean A. McCarthy: The responses that we're seeing in the confirmed resist responses, we've seen a five and six milligrams and remember that we began this dose escalation as seven micrograms. So.

Sean A. McCarthy: The range of doses, where we're seeing activity is actually really consistent with our.

Sean A. McCarthy: Our predictions.

Sean A. McCarthy: For modeling of where the biologically effective range would be so we think we're in the zone.

Sean A. McCarthy: We do believe, however, because of the safety profile, we can dose higher. Whether that will help or not, I don't think we know. I think all of us in the T cell engager field are kind of trying to figure this out. And if you look at Amgen's tarlatumab, I mean, they went all the way to 100 and concluded in the end that 10 milligrams was the dose to move forward because 100 didn't give significant additional efficacy.

Roger Song: We do believe however, because of the safety profile.

Sean A. McCarthy: We can dose higher.

Speaker Change: Whether that will help.

Speaker Change: I think all of us in the T cell engage a field.

Speaker Change: Trying to figure this out and if you look at Amgen style at all.

Speaker Change: The way to a 100.

Sean A. McCarthy: And concluded in the end at 10 milligrams was the dose to move forward because the 100 didn't give significant additional efficacy. So I think we've got to learn more but we are ready.

Sean A. McCarthy: So I think we want to learn more, but we're really very encouraged that we have this. The Clean Safety Profile with EGFR has exceeded our expectations, and it will allow us to dose escalate further, and we'll do that, and we'll see where it takes us.

Speaker Change: Very encouraged that we have this.

Sean A. McCarthy: Clean safety profile with Egfr.

Sean A. McCarthy: <unk> our expectations.

Speaker Change: It will allow us to dose escalate further and we will do that and we'll see where it takes us.

Speaker Change: Got it.

Sean A. McCarthy: My follow-up question is related to your partner, Amgen. So, this data, have you shared with the partner? And if so, any initial feedback?

Speaker Change: My follow up question is related to your partner Amgen. So this data have you share with with.

Sean A. McCarthy: With the partner and if so any initial feedback.

Sean A. McCarthy: And also, understanding you will give a data update by the end of the year, what you are looking for in order for both of you, two parties, to make the Phase 1B study design. Yeah, great questions. So with Anjan, let's take a little step back and talk about, we'll just recap the agreement that we have with Amgen. So we're obviously running.

Sean A. McCarthy: Also understanding you well.

Sean A. McCarthy: Give a data update by the end of the year.

Speaker Change: What you are looking for in order for.

Speaker Change: Most of you have two parties to make the phase <unk> study design.

Sean A. McCarthy: Sure.

Speaker Change: Yes, great questions, so with Amgen, let's take a little step back and talk about will just recap the.

<unk>.

Speaker Change: <unk>.

Speaker Change: The agreement that we have with Amgen. So we're obviously running.

Sean A. McCarthy: The phase one study.

Speaker Change: <unk>.

Speaker Change: We do share data with them as it emerges.

Sean A. McCarthy: We are also responsible for running the phase one b.

Sean A. McCarthy: Once we get that up and running in the transition from phase one to phase one b. It's a decision that we will take jointly.

Sean A. McCarthy: With Amgen and of course, the goal would be to in phase one b to enrol specific egfr positive tumor types of wastewater now quite obviously.

Speaker Change: We'd be pancreatic we would assume.

Sean A. McCarthy: We would assume based on this exciting signal that we've seen. So, because the way that enrollment has unfolded, you know, we still haven't enrolled many patients in lung or head and neck, for example. We do want to bring in a few more patients and get some additional experience in those tumor types before we have a conversation with Angen later in the year about what the Phase 1B strategy would be. So, the update later this year could be a couple of things.

Sean A. McCarthy: Based on this exciting signal that we've seen.

Sean A. McCarthy: So we because we.

Sean A. McCarthy: The way that enrollment has unfolded, we still have just not enrolled many patients in lung.

Speaker Change: Our head and neck for example.

Speaker Change: We do want to bring in a few more patients get some additional experienced in those tumor types before we have the conversation with Amgen later in the year about what the phase <unk> strategy would be so the update later this year could be a couple of things that could be.

Sean A. McCarthy: It could be additional data from, you know, we would ballpark, we should have another 10 or so patients of data by the end of the year. It could also be an operational update, you know, that we've agreed with Angen on the next steps. We just have to, you know, have that dialogue with them.

Sean A. McCarthy: <unk>.

Speaker Change: Additional data from that we would ballpark.

Speaker Change: We should have by end of year.

Speaker Change: <unk> patients of data.

Sean A. McCarthy: It could also be.

Sean A. McCarthy: And operational update that we've agreed with Amgen on the next steps.

Sean A. McCarthy: We just have to.

Sean A. McCarthy: You don't have that dialogue.

Speaker Change: With them, but in terms of that perspective on the data I think that's a question best asked of them.

Sean A. McCarthy: But in terms of, you know, their perspective on the data, I think that's a question best asked of them at this point in time. But obviously, we're really excited by our progress.

Sean A. McCarthy: At this point in time, but obviously, where we're really excited by our progress.

Speaker Change: Excellent. Thank you.

Sean A. McCarthy: Thank you. You're welcome. Thank you. And for the next question, it comes from the line by Joe Catanzaro from Pierce Sandler.

Speaker Change: Youre welcome.

Sean A. McCarthy: Thank you and for our next question. It comes from the line of Joe Catanzaro from Piper Sandler. Please go ahead.

Joseph Michael Catanzaro: Everybody. Thanks for taking my questions and exciting data here I guess, maybe first one on the Egfr mediated talks that Youre seeing I guess my question is like what do you think is happening is that some small amount getting unmask and periphery or maybe a small amount getting unmasking the tumor and then.

Operator: Please go ahead. Hey, everybody, thanks for taking my questions and giving me such exciting data here. I guess maybe the first one on the EGFR mediated tox that you're seeing. I guess my question is, what do you think is happening?

Joseph Michael Catanzaro: Is that some small amount getting unmasked in the periphery, or maybe a small amount getting unmasked in the tumor and then reentering circulation? And is that the toxin that you're seeing? Typical of some sort of historical EGFR experience, say, Cytuximab, or is there anything indicative that it's T-cell targeting of EGFR? Thanks, and I may have one follow-up. Yeah, hi Joe, thanks for the question.

Joseph Michael Catanzaro: Re entering circulation.

Joe: That talks that you are seeing typical sort of historical egfr experienced face it tucks in Nab or is there anything indicative that its T cell targeting of Egfr on normal tissue.

Speaker Change: And I may have one follow up.

Speaker Change: Yes, Hi, Joe Thanks for the question.

Sean A. McCarthy: Well, first of all, let me say that we're really, really pleased with the very low incidence of grade 3 rash in this study. We only have one patient out of 35 patients with a grade 3 treatment-related rash. That's a significant achievement, we think, because it's unlocked the opportunity to use this mechanism to shrink tumors that otherwise couldn't be shrunken with DGFR. So we're very, very pleased about that. Obviously, early days, more work to do, but we're encouraged. With any drug, you're going to see some side effects—you're going to see ABs. It's very hard to say where they're coming from. Is it local?

Joseph Michael Catanzaro: Well.

Speaker Change: First of all let me say that.

Sean A. McCarthy: We're really really pleased with the very low incidence of grade three rash in this study.

Joe: We only have one patient over the 35 patients with grade three treatment related rash.

Sean A. McCarthy: That's a significant achievement we think.

Sean A. McCarthy: Because it's unlocks the opportunity to use this mechanism to.

Sean A. McCarthy: Otherwise couldnt be shrunk with Egfr. So we're very very pleased about that obviously early days more work to do but we're encouraged.

Speaker Change: With any drug youre going to see some.

Speaker Change: Youre going to see Aes, it's very hard to say what are they where are they coming from is it local is a systemic.

Sean A. McCarthy: Is it systemic? You know, we don't know, and we may never know, and in a way, it might not matter that much because it's all about the risk-benefit profile, and we're obviously delivering something we think is very important here, at least initially, for patients with very late-stage. On the type of rash that we see, cytostomab rash is typically an acne-form rash We see some of that, you know, grade 1, grade 2.

Speaker Change: We don't know and we May never know.

Sean A. McCarthy: In a way it might not matter that much because it's all about the risk benefit profile and where we're obviously delivering something we think we have very important efforts.

Sean A. McCarthy: At least initially for patients with very late stage pancreatic cancer.

Sean A. McCarthy: I would say.

Speaker Change: Yeah.

Sean A. McCarthy: The type of rash that we see in a cetuximab rashes is typically the acne form rash.

Sean A. McCarthy: <unk>.

We are.

Speaker Change: We see some of that grade one grade two there also.

Sean A. McCarthy: There are also, as Wayne mentioned, maculopapular rashes, which are maybe more T-cell-involved T-cells. So I think we're going to have to learn more about it, but we're not worried about it because it's mostly grade 1, 2. In fact, across the entire study, the incidence of rash across all 35 patients was 40%, and just about all grade 1, 2 and manageable. So we're really encouraged by the AE profile here, not to mention the CRS profile, which really, quite frankly, surprised us to the upside. Yeah, thanks, that's helpful.

Sean A. McCarthy: Wade mentioned Macchiato popular.

Sean A. McCarthy: Rashes, which are maybe more T cell.

Sean A. McCarthy: <unk> T cells.

Sean A. McCarthy: So I think we're going to have to learn more about it but we're not worried about it because it's mostly grade one two if I had across the entire study the incidence of rash across the entire 35 patients was 40%.

Sean A. McCarthy: Just about all grade one two and manageable. So we're really encouraged by the AE profile here not to mention the Crs profile was really quite frankly surprised us to the upside.

Speaker Change: Yeah. Thanks, that's helpful. I guess, maybe my follow up for the pancreatic cancer patient that had that deep response then.

Wayne Chu: I guess maybe my follow-up for the pancreatic cancer patient that had that deep response and subsequent progression. Wondering if you could maybe elaborate a little bit more on that progression event, a new lesion, growth of a target lesion, if it was a new lesion, maybe we're able to profile, going on. Just anything you could say there, I guess, would be... Yeah, I could provide some details on that. This is a patient that, you know, was treated with a six milligram non-step dose, had a confirmed partial response, that's, you know, strikingly with over 80% reduction in measurable tumor burden. And the patient did progress based on growth of the target lesion from the NADER, as well as the appearance of, I think, one new target lesion. Sorry, I have one new lesion.

Wayne Chu: Subsequent progression wondering if you could maybe elaborate a little bit more on that progression event.

Wayne Chu: Was it a new lesion growth or a target lesion.

Wayne Chu: If it was a new lesion, maybe youre able to sort of profile it and see what's going on just anything you can say there I guess would be would be interesting.

Speaker Change: Yeah, I can provide some details on that.

Wayne Chu: So that was the nature of the progression in that particular patient, but all through that treatment course, the patient did quite well clinically. I mean, it was just based on the radiographic progression that we had. Okay, thanks. And maybe I could just squeeze in one more quick one, maybe going back to an earlier question.

Speaker Change: This is a patient that.

Speaker Change: But for you with the six milligram Nonslip dosing had a confirmed partial response.

Wayne Chu: Yes.

Speaker Change: Strikingly with over 80% reduction in measurable tumor burden the patient did progress based on.

Wayne Chu: Growth of the target lesion from the nadir as well as the appearance of I think of one new new target lesion on non I'm, sorry, one new lesion allow us the nature of the progression on that particular patient, but all through that.

Wayne Chu: Stream of course that patient did quite well clinically and it was just based on the radiographic progression there.

Speaker Change: Okay, Thanks, and maybe if I could just squeeze in one more quick one maybe going back to an earlier question.

Sean A. McCarthy: If you could maybe speculate more on what you think is maybe going on in MSS-CRC, it seems mechanistically like you're seeing T-cell infiltration, but that's not translating to tumor reduction. So I'm wondering if you have any other sort of hypotheses about what may be going on in those patients. Thank you. I think mechanistically, it's really interesting.

Speaker Change: If you can maybe speculate more on what you think it may be going on in MSS CRC.

Sean A. McCarthy: <unk> seen mechanistically like Youre seeing T cell infiltration, but that's not translating to tumor.

Sean A. McCarthy: Production. So I'm wondering if you have any other sort of hypotheses of what may be going on in those patients.

Sean A. McCarthy: Okay.

Sean A. McCarthy: When we think about how T cell engagement works overall, right, the CD3, CD3 combined with a tumor antigen, you know, we think of these typically as being MHC non-restricted mechanisms. That may very well be what's going on, but there could be more that's necessary to really mount an anti-tumor response. I think we're, you know, again, in the field. I think there's more to be learned about specifically how CD3 T cells engage kill cancer cells.

Sean A. McCarthy: I think mechanistically, it's really interesting.

Sean A. McCarthy: When we think about how T cell engages work overall CD three.

Sean A. McCarthy: <unk> combined with a tumor antigen.

Sean A. McCarthy: These typically as being MHC nonrestricted mechanisms that may very well very well.

Sean A. McCarthy: Going on but there could be that could be more of this necessary. So very much an antitumor response I think we're again in the field I think theres more to be.

Sean A. McCarthy: <unk> about specifically, how <unk> T cell engages kill cancer cells, clearly, we're doing it in pancreatic cancer, where getting the T cells there in CRC.

Sean A. McCarthy: Clearly, you know, we're doing it in pancreatic cancer. We're getting the T cells there in CRC, but it draws one's attention to think about what combination strategies could get you to the actual objective, you know, tumor responses. So, I think more work to do there in some of the basic science, and then also clinical work that we can do in terms of clinical combinations is quite intriguing. Thanks for the update, and thanks for taking my question. Thank you. And for your next question, it comes from Delilah.

It draws attention to thinking about what combination strategies could get you to actual objective tumor responses. So I think more work to do there and some of the basic science.

Delilah: And then also clinical work that we can do.

In terms of clinical combinations.

Delilah: Quite intriguing.

Speaker Change: Yeah. Okay. Thanks, Thanks for the update and thanks for taking my question.

Delilah: You bet.

Delilah: Thank you and for your next question comes from July <unk> from BMO capital markets. Please go ahead.

Operator: I've answered their call from BMO Capital Markets. Please go ahead. Great. Thanks for taking the time to answer the question. Just wondering if you could maybe talk through your current thoughts on sort of the step versus the non-step dosing, particularly in the pancreatic patients that sort of had the response and how you're kind of thinking about potentially moving one or the other option forward as you sort of expand the patients. And then, I don't know if you said this specifically, but about sort of the EGFR expressions across sort of the patients that you've seen

Speaker Change: Great. Thanks for taking the question.

Operator: If you could maybe talk through your current thoughts on sort of the.

Operator: The step versus the non stop dosing, particularly in the pancreatic.

Operator: Patients that sort of had to response and how you're kind of thinking about potentially moving one or the other option forward as you sort of expand the patient and then.

Operator: Is it that you're going to, moving forward, look at EGFR expressions? Or is there an opportunity to kind of look at EGFR expressions across the folks that you've already sort of enrolled in the study? I don't know if I caught that correctly.

Operator: Don't know if you said this specifically but.

Operator: About sort of the egfr expressions across sort of the patients.

Operator: That you've seen so far is it that youre going to moving forward you will look at Egfr expression or is there an opportunity to kind of look at egfr expression across the folks that you've already sort of enrolled in the study I don't know if I caught that correctly. Thank you.

Speaker Change: Yeah. Thanks. Thanks.

Etzer Darout: Thank you. Yeah, thanks. Thanks, Ed, sir.

Speaker Change: In terms of moving forward with Stefan Nonstop, we obviously haven't made a decision on that yet, but I would say.

Speaker Change: Based on our experience to date more likely that our phase one b doses will be set.

Etzer Darout: Our strategies.

Etzer Darout:

Etzer Darout: Because it's allowing us to get to a significantly higher target doses.

Sean A. McCarthy: In terms of, you know, moving forward with step or non-step, we obviously haven't made a decision on that yet, but I would say, based on our experience to date, that it's more likely that our phase 1B doses will be step strategies because it's allowing us to get to significantly higher target doses. And we do think there's a dose response here of sorts, you know, so more to be learned there We'll also likely take it.

Etzer Darout: We do think there's a dose response here.

Sean A. McCarthy: Of sorts.

Sean A. McCarthy: So.

Sean A. McCarthy: More to be learned there.

Sean A. McCarthy: Sure.

Sean A. McCarthy: We will also likely take.

Sean A. McCarthy: When you think about project optimist considerations, we'll likely want to take more than one dose and schedule it into phase 1b to gain further experience of the drug candidate, not only in pancreatic cancer but also in other tumors as well. In terms of EGFR, it's surprising, actually, how, (inaudible) how should I put this? The available assay for EGFR, or assays for EGFR by IHC, let's just say they're not perfect. And so we're not sure how much one would want to rely on them moving forward, particularly because it doesn't seem from our early data that this is a straightforward ADC type thing where a high target is required for activity.

Sean A. McCarthy: When you think about project Optimus considerations will likely want to take more than one dose.

Sean A. McCarthy: Schedule into phase <unk>.

Sean A. McCarthy: Gain further experience of.

Sean A. McCarthy: The drug candidate.

Sean A. McCarthy: Not only in pancreatic but also in other in other tumors as well.

Sean A. McCarthy: In terms of Egfr.

Sean A. McCarthy: It's surprising actually how.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: How should I put this.

Sean A. McCarthy: The available assay for Egfr assays for Egfr by IAC, Let's just say, it's not perfect and so we're not sure how much one would want to rely on it moving forward, particularly because it doesn't seem from our early data.

Sean A. McCarthy: As a straightforward.

Sean A. McCarthy: You know, these drugs, drugs like T cell engagers, would be predicted to be active at low target levels because of the mechanism of the amplified mechanism of tumor killing where one T cell can kill multiple tumor cells. I think we've got more to learn there, and that's why we may not be needing or leveraging eGFR selection on a go-forward basis based on what we've seen so far.

Sean A. McCarthy: ADC type thing, where you high target is required for activity. These drug drug slide T cell engages.

Sean A. McCarthy: <unk> would be predicted to be active low target levels.

Sean A. McCarthy: Because of the mechanism of <unk>.

Sean A. McCarthy: The amplified mechanism of tumor killing <unk> T.

Sean A. McCarthy: T cells can kill multiple cheat yourselves so.

Sean A. McCarthy: I think we've got more to learn there.

Speaker Change: That's why we're where.

Sean A. McCarthy: We may not be needing or leveraging egfr selection on a go forward basis based on what we've seen so far.

Speaker Change: Got it thank you.

Speaker Change: Youre welcome.

Speaker Change: One moment for your next question.

Sean A. McCarthy: Thank you. You're welcome. One moment for the next question. And for our next question, it comes from the line of Anupam Rama from J.P. Morgan. Please go ahead. Hey, guys, how are you?

Anupam Rama: And for our next question comes from the line of <unk> Rama from JP market. Please go ahead.

Anupam Rama: Hey, guys how are you. Thanks.

Operator: Thanks so much for the data update. Can you comment? Was there anything in the baseline characteristics? number of prior treatments? I think the PDAC case study that you said was three lines of therapy or otherwise that might be predictive of a response. I think based on the first question, EGFR expression didn't correlate. And then can you comment, and I'm sorry if I missed this. The other three stable disease patients. What was their duration?

Speaker Change: Thanks, so much for the.

Operator: The data update.

Operator: Can you comment.

Operator: Was there anything in the baseline characteristics.

Operator: Number of prior treatments I think the PDR case study that you said was three lines of therapy or otherwise that might be predictive of response I think based on the first question Egfr expression didn't correlate and then can you comment and I'm, sorry, if I missed that.

Operator: The other three stable disease patients.

Operator: What was their duration. Thanks, so much.

Operator: Thanks.

Anupam Rama: Thanks, Anupam. I'll take the first question in terms of... You know... which I think was editing out patient characteristics that could have been predictive of response. And I'd say, no, not really.

Speaker Change: I'll take the first question in terms of.

Anupam Rama: Yeah.

Anupam Rama: Which I think was there anything in the patient characteristics that could have been predictive of response and I'd say no not really.

Anupam Rama: Again these are all pretty late line patients.

Sean A. McCarthy: Again, these are all pretty late-line patients, and aside from EGFR, Yeah, we did show, that said, Wayne showed a slide of a pretreatment biopsy of a patient with pretty high levels of pretreatment CD8-positive cytotoxic T cells, which is intriguing and certainly could have contributed to the response. And so that's something that we have observed.

Sean A. McCarthy: Aside from Egfr.

Speaker Change: Yes, we did show.

Sean A. McCarthy: That said <unk> showed a slide.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: A pretreatment biopsy of a patient.

Sean A. McCarthy: Pretty high levels of pre treatment.

Sean A. McCarthy: Positive cytotoxic T cells, which is intriguing.

Sean A. McCarthy: Yes.

Sean A. McCarthy: And certainly could have contributed to the response and so.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: That's something that we have observed we don't have that data systematically across the whole study that's difficult data to get.

Sean A. McCarthy: We don't have that data systematically across the whole study. That's difficult data to get for every patient, but it is intriguing. In terms of stable disease, Wayne can address that question real quick. Yeah, so as we, you know, showed in the swim lane plot during the presentation, there were a number of patients who were able to maintain stable disease through at least one tumor response. And, you know, that included a smattering of patients that had durable, stable disease through two tumor responses, but otherwise, patients were able to achieve stable disease, and then it was followed by progressive disease. I do think it's important to reemphasize that, you know, these pancreatics are very, as everyone knows, it's a very rapidly progressing disease.

Wayne Chu: For every patient, but it is intriguing.

Sean A. McCarthy: <unk>.

Wayne Chu: In terms of the stable disease.

Sean A. McCarthy: Wayne can address that question real quick.

Wayne Chu: So as we showed in the swim lane plot during our presentation.

Wayne Chu: There were a number of patients who were able to maintain a stable disease for at least one.

Wayne Chu: Tumor response.

Wayne Chu: And Spattering and that included a smattering of patient that had durable stable disease through tumor to tumor responses, but otherwise.

Wayne Chu: Otherwise patients were able to achieve a stable disease.

Wayne Chu: Then it was followed by progressive disease.

Wayne Chu: I do think it's important to reemphasize that.

Wayne Chu: These, these are patients who, for the most part, have had, you know, three or four prior surgeries. And so, you know, this, this, So, yeah, we think this is really exciting data. Thanks so much for taking our questions. Thank you, and as a reminder, to ask a question, simply press star 11 on your telephone keypad. And for the next question, it comes from the line of Mitchell Kapoor from HFC Wainwright. Please go ahead.

Mitchell Swaroop Kapoor: Again, the pancreatic is a very as everyone knows it's a very rapidly progressing disease. These are patients who for the most part have had three or four priors and so.

Wayne Chu: This.

Mitchell Swaroop Kapoor: So we think this is really exciting data.

Mitchell Swaroop Kapoor: Thanks, so much for taking our questions.

Mitchell Swaroop Kapoor: Thank you and as a reminder to ask a question simply press star one on your telephone keypad.

Wayne Chu: Our next question at constant a line of Mitchell Kapoor from HFC Wainright. Please go ahead.

Mitchell Swaroop Kapoor: Hi, everyone. Congrats on the positive data I wanted to ask about the.

Operator: Hi everyone, congrats on the positive data. I wanted to ask about the total eight patients with tumor reductions. The others, well, I guess if you could just broadly comment on what a spider plot for these patients might look like. Are you seeing a trend in depth of response over time? Or how are we seeing those tumor reductions evolve? Yeah, spider. I mean, it's early days.

Operator: Total eight patients with tumor reductions.

Operator: The other well I guess, if you could just broadly comment on what a spider plot for these patients might look like are you seeing a trend in depth of response over time or how are we seeing this tumor reductions evolves.

Operator: Yes.

Mitchell Swaroop Kapoor: I think that those eight patients, obviously two of them are the pancreatic patients, you can see them in the waterfall plot. I think there's encouragement there in terms of the fact that escalation continues, we'll keep pushing the dose here. So, you know, at this point, I think it's fair to say the spider plot will be relatively immature.

Operator: It's early days I think that those those eight patients two of them are the pancreatic patients and you can see them in the waterfall plot.

Mitchell Swaroop Kapoor: I think there is encouragement there in terms of the fact that escalation continues we'll keep pushing the dose here.

Mitchell Swaroop Kapoor: So at this point I think it's fair to say despite of what will be relatively immature.

Speaker Change: Okay. Thank you and.

Sean A. McCarthy: Okay, thank you. And could you just comment on the other confirmed partial response patient and how much duration of follow-up that patient had? That patient, again, was treated at the six milligram non-step dosing schedule, had a confirmed partial response, and that patient remained on study about eight, on study treatment for approximately 18 weeks before experiencing progressive disease. Okay, great.

Sean A. McCarthy: Could you just comment on the other confirmed partial response patient and how much duration of follow up that patient.

Sean A. McCarthy: So that patient.

Sean A. McCarthy: <unk> was treated at the six milligram non step dosing schedule.

Sean A. McCarthy: Confirmed partial response and that patient remained on study about eight on study treatment approximately 18 weeks before having progressive disease.

Speaker Change: Okay, great. Thank you for taking my questions.

Wayne Chu: Thank you for taking my questions. You're welcome. Thank you, and I'm showing no further questions. I would now like to turn the conference back to Dr. Sean McCarty, CytomX's Chairman and CEO, for a closing remark. Great, thank you very much.

Speaker Change: Youre welcome.

Sean A. McCarthy: Thank you and I'm showing no further questions I would now like to turn the conference back to Dr. Sean Mccarthy, <unk>, Chairman and CEO for closing remarks.

Sean A. McCarthy: Great. Thank you very much and thanks, everyone for listening in today.

Sean A. McCarthy: And thank you everyone for listening in today. CytomX has made terrific progress so far in 2024, and we look forward to providing additional updates as the year progresses and as we continue to build our company for the long term to make the biggest difference we can for patients. And so, thank you very much. Have a good evening.

Sean A. McCarthy: This has made terrific progress so far in 2024, and we look forward to providing additional updates as the year proceeds and as we continue to build our company for the long term to make the biggest difference we can for patients and so thank you very much have a good evening.

Speaker Change: This concludes today's conference call. Thank you for participating and you may now disconnect.

Operator: This concludes today's conference call. Thank you for participating, and you may now disconnect. Goodbye. You can buy these coils, shapes, & designs from our ETSY store!

Operator: Goodbye.

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unknown: Link in the description below, This is a production of the Center for Autism and Related Disorders, the Center for Autism in the United States, and the Center for Autism in the United States Academy of Sciences. This program is brought to you by the Center for Autism and Related Disorders. This is a production of the Center for Autism and Related Disorders. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Copyright © 2020, New Thinking Allowed Foundation, Copyright © 2020 Mooji Media Ltd. All Rights Reserved.

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unknown: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? Copyright © 2020, New Thinking Allowed Foundation ? ? ? ? ? ? Good day and thank you for standing by. Welcome to the CytomX Therapeutics first quarter 2024 financial results conference call. At this time, all participants are in the listen-only mode.

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unknown: Good day and thank you for standing by welcome to the <unk> Therapeutics first quarter 2024 financial results Conference call.

Speaker Change: At this time all participants are in a listen only mode.

unknown: After the speaker's presentation, there will be a question and answer session, and to ask a question during the session, you will need to press star one on your telephone, and you will then hear an automated message advising that your hand is raised.

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Christopher W. Ogden: To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would like to hand the conference over to your speaker today, Chris Ogden, CytomX's Senior Vice President, Finance and Accounting. Please go ahead.

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Christopher W. Ogden: Please be advised that today's conference is being recorded.

Christopher W. Ogden: I would now like to hand, the conference over to your Speaker today, Chris Ogden Cytolysis Senior Vice President Finance It accounting. Please go ahead.

Christopher W. 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 will be making four 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.

Christopher W. Ogden: Thank you good afternoon, and thank you for joining us before.

Christopher W. Ogden: Before we begin I would like to remind everyone that during this call we'll be making forward looking statements.

Christopher W. Ogden: Forward looking statements relate to the future theyre subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control.

Christopher W. Ogden: 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 included a summary of our first quarter 2024 financial results and highlights recent progress at CytomX. We also issued a press release today announcing positive initial Phase 1a dose escalation data for monotherapy CX904, which will be the primary focus of today's call.

Christopher W. Ogden: Important risks and uncertainties are set forth in our most recent public filings with the SEC at SEC Gov.

Christopher W. Ogden: We undertake no obligation to update any forward looking statements.

Christopher W. Ogden: Whether as a result of new information future developments or otherwise.

Christopher W. Ogden: Earlier. This afternoon, we issued a press release that includes a summary of our first quarter 2024 financial results and highlight recent progress at photonics.

Christopher W. Ogden: We also issued a press release today announcing positive initial phase one dose escalation data for monotherapy CX 904.

Christopher W. Ogden: Which will be the primary focus of today's call.

Christopher W. Ogden: We encourage everyone to read today's press releases and the associated materials which have been filed with the SEC. Additionally, the press releases or according to this call and our SEC filings can be found under the investors and news section of our website.

Christopher W. Ogden: We encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC.

Christopher W. Ogden: Additionally, the press releases or recording of this call and our SEC filings can be found under the investors and news section of our website.

Christopher W. Ogden: With me on the call today are Dr. Sean Mccarthy.

Christopher W. Ogden: Thomas <unk>, Chief Executive Officer and Chairman.

Christopher W. Ogden: And Dr Wayne Chu.

Christopher W. Ogden: Alex the Chief Medical Officer.

Christopher W. Ogden: Sean will provide an update on the overall pipeline and also outline cytolysis broader strategy for math T cell engagements.

Christopher W. Ogden: Wayne will then give an update on the CX 904 phase one dose escalation study before Sean provides clothing got it can we open up the call for Q&A.

Christopher W. Ogden: With me on the call today are Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman, and Dr. Wayne Chu, CytomX's Chief Medical Officer. Sean will provide an update on the overall pipeline and also outline CytomX's broader strategy for mass T cell engagement. Wayne will then give an update on the CX904 Phase 1 Dose Escalation Study before Sean provides closing comments, and we open up the call for Q&A. With that, I'll now turn the call over to Sean. Thanks, Chris. And good afternoon, everyone.

Christopher W. Ogden: With that I'll now turn the call over to Sean.

Sean A. McCarthy: It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our Phase 1 study of our eGFR-targeted probody T-cell engager, CX904. CytomX is highly focused on addressing major unmet needs in oncology using our ProBody Therapeutic Platform, a proprietary antibody masking strategy designed to improve the therapeutic window for multiple antibody modalities through tumor localized activation We are leveraging our ProBody therapeutic platform to discover and develop new cancer therapies based on masked T-cell engagers, masked ADCs, and masked cytokines.

Sean A. McCarthy: Thanks, Chris and good afternoon, everyone. It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our phase one study of our Egfr targeted priority T cell engages CX 904.

Sean A. McCarthy: <unk> is highly focused on addressing major unmet needs in oncology using a <unk> therapeutic platform, our proprietary antibody masking strategy designed to improve the therapeutic window for multiple antibody modalities through tumor localized activation.

Sean A. McCarthy: We are leveraging our priority therapeutic platform to discover and develop new cancer therapies based on masked T cell engages masked adcs and mask cytokines.

Sean A. McCarthy: Our broad and deep pipeline encompasses more than 15 active programs, including three clinical stage molecules and significant retained commercial rights. Strategic partnering has been a long-standing component of our corporate strategy, and we're proud to be working closely with Bristol-Myers Squibb, Amgen, Astellas, Regeneron, and Moderna on multiple pro-body therapeutic programs. We continue to be in a strong financial position with 150 million dollars of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding.

Sean A. McCarthy: Our broad and deep pipeline encompasses more than 15 active programs, including three clinical stage molecules and a significant retained commercial rights.

Sean A. McCarthy: Strategic partnering is a longstanding components of our corporate strategy and we're proud to be working closely with Bristol Myers Squibb, Amgen, Astellas Regeneron and Mcdonough on multiple priority therapeutic programs.

Sean A. McCarthy: We continue to be in a strong financial position with $150 million of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding.

Sean A. McCarthy: CytomX is very strong organizationally, with integrated R&D capabilities, continued investment in our core technology, and a deeply experienced team dedicated to our vision of transforming lives with safer, more effective therapies. Moving to slide six, the CytomX product design strategy using our ProBody therapeutic platform is informed by more than a decade of experience and seeks to balance target selection, masking strategy, and effective function to make meaningful impact in key areas of unmet need in oncology.

Sean A. McCarthy: So that makes us very strong organizationally with integrated R&D capabilities continued investment in our core technology and a deeply experienced team dedicated to our vision of transforming lives with safer more effective therapies.

Sean A. McCarthy: CX904 brings the EGFR target together with T-cell engagement via CD3 with the goal of T-cell-mediated killing of EGFR-positive tuber types, potentially including those for which conventional antibodies have not shown activity. CX2051 is our masked, conditionally activated ADC that integrates the high potential of EPCAM as a cancer cell target with the potency of a TOPA1 inhibitor payload, ideally suited CX801 leverages the potent activity of the cytokine interferon alpha, which in this case is the effector mechanism itself. Our mast interferon is designed to locally activate the intratumoral immune microenvironment with potential to drive responses across multiple cancer types, including melanoma, renal cell carcinoma, and head and neck squamous cell carcinoma.

Sean A. McCarthy: Moving to slide six the cytogenetics product design strategy using our priority therapeutic platform is informed by more than a decade of experience and seeks to balance target selection masking strategy and effector function to make meaningful impact in key areas of unmet need in oncology.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: CX 904 brings the Egfr target together with T cell engagement via CD three with the goal of T cell mediated killing of Egfr positive tumor types potentially including those for which conventional antibodies have not shown activity.

Sean A. McCarthy: <unk> 051 is a marked conditionally activated ADC that integrates the high potential of <unk> as a cancer cell target with the potency of a total one inhibitor payload ideally suited we believe it's a high <unk> expressing tumors like colorectal cancer.

Sean A. McCarthy: Oh, one leverages the potent activity of the cytokines interferon Alpha which in this case is the effective mechanism itself.

Sean A. McCarthy: <unk> is designed to locally activate the intra tumoral immune microenvironment with potential to drive responses across multiple cancer types, including melanoma renal cell carcinoma in head and neck squamous cell carcinoma.

Sean A. McCarthy: Q1 was an extremely productive quarter. Besides <unk>, we are executing to our plans and we're making progress across the full breadth of our pipeline. Today. We are announcing positive initial phase one dose escalation data from monotherapy CX 904, our Egfr CD three T cell engagement in solid tumor.

Sean A. McCarthy: Q1 was an extremely productive quarter for CytomX. We are executing to our plans, and we're making progress across the full breadth of our pipeline. Today, we're announcing positive initial phase 1a dose escalation data for monotherapy CX904, our EGFR-CD3 T cell engager in solid tumors. And this is the main topic of our update here today.

Sean A. McCarthy: And this is the main topic of our update here today.

Sean A. McCarthy: In addition to our exciting progress with CX904, during Q1, the first dose cohort cleared in the Phase 1 clinical study of 2051, our ADC-targeting EPCAM. This study is focused largely on colorectal cancer, and we anticipate initial data in the first half of 2025. Also, during Q1, Phase 1 study initiation activities continued for CX801 masked interferon alpha, including the execution of an agreement with Merck to supply Keytruda for combination with CX801, and we announced that agreement last night. Initial data from the 801 program are also anticipated in 2025.

Sean A. McCarthy: In addition to our exciting progress with CX 904 during Q1, the first dose cohort in the phase one clinical study of <unk> five one our ADC targeting <unk>. This study is focused largely in colorectal cancer and we anticipate initial data in the first half of 2025.

Sean A. McCarthy: Also during Q1 phase one study initiation activities continued for CX 801.

Sean A. McCarthy: Interferon alpha, including the execution of an agreement with Merck to supply Keytruda for combination with CLSA Taiwan.

Sean A. McCarthy: That agreement last night.

Sean A. McCarthy: Initial data from the 801 program is also anticipated in 2025.

Sean A. McCarthy: We continue to make excellent progress across our collaborations, including earning $10 million in milestones under our T-cell engagement by specific collaboration with Astellas, which was for preclinical progress on the first two programs in the Alliance. We're also delighted to welcome Dr. Zhen Xu to our board during Q1.

Sean A. McCarthy: We continue to make excellent progress across our collaborations, including earning $10 million of milestones under our T cell engaging by specific caliber collaboration with Astellas.

Sean A. McCarthy: That was for preclinical progress on the first two programs in the alliance.

Sean A. McCarthy: We are also delighted to welcome Dr Sue to our board.

Sean A. McCarthy: During Q1, so it really productive start to 2020 for precise techniques on all fronts.

Sean A. McCarthy: So a really productive start to 2024 for CytomX on all fronts, and our current clinical pipeline is really gaining momentum. And we have a very exciting 12 to 24 months ahead of us.

Sean A. McCarthy: Current clinical pipeline is really gaining momentum and we have a very exciting 12 to 24 months ahead of us.

Sean A. McCarthy: Moving now to our T cell engages strategy. T cell engagement by specific antibodies, of course, has enormous potential for the treatment of cancer and first demonstrated meaningful clinical benefit in hematologic malignancies. Looking at the solid tumor landscape for T cell engages, however, it's taken time to see meaningful clinical progress.

Sean A. McCarthy: Moving now to our T cell engagement strategy.

Sean A. McCarthy: T cell engaging bi specific antibodies of course have enormous potential for the treatment of cancer and first demonstrated meaningful clinical clinical benefit in hematologic malignancies.

Sean A. McCarthy: At the solid tumor landscape for T cell engages however, it has taken time to see meaningful clinical progress and for this modality to really breakthrough in solid tumors. There are some significant challenges to overcome.

Sean A. McCarthy: And for this modality to really break through in solid tumors, there are some significant challenges to overcome. Notably, T cell engagers have very high potency, and this potency can lead to toxicities in normal tissues, where the tumor actinid of interest may also be present. Another key limitation for T cell engagement in solid tumors is cytokine release syndrome, resulting from systemic binding to CD3 on T cells and also neurotoxicity in the form of ICAT.

Sean A. McCarthy: Notably T cell engages bring very high potency in this purchase he can lead to toxicity than normal tissues, where the tomb ratcheted of interest may also be present.

Sean A. McCarthy: Another key limitation for T cell engages in solid tumors as cytokine release syndrome, resulting from systemic binding to <unk> on T cells and also neurotoxicity in the form of icons.

Sean A. McCarthy: At CytomX, we have a broad-based program focused on masking T cell engagers to decrease tumor antigen binding in normal tissues and also decrease CD3 binding in the periphery, thereby improving therapeutic index. In addition to our internal programs, we're working with partners Amgen, Astellas, Regeneron, and BMS in this exciting space. CX904 is our lead program in the T-Cell Engage area, and I'd like to spend a few minutes now walking through the history and structure of this molecule.

Sean A. McCarthy: At <unk>, we have a broad based program focused on masking T cell engages to decreased tumor antigen binding in normal tissues and also decreased CD three binding in the periphery, thereby improving therapeutic index.

Sean A. McCarthy: In addition to our internal programs, we're working with partners Amgen Astellas Regeneron and BNS in this exciting space CX 904, as our lead program in the T cell engage area and I'd like to spend a few minutes walking through the history and structure of this molecule.

Sean A. McCarthy: Yes.

Sean A. McCarthy: We've had a longstanding interest in EGFR at CytomX; our seminal publication of the first ever successful antibody masking was focused on the EGFR binding antibodies to Tuxomab, for which we showed a marked reduction in systemic skin rash for the masked antibody compared to the unmasked version. These findings set the stage for the evolution of the monospecific EGFR probody into our CX904 bispecific T-cell engager.

Sean A. McCarthy: We've had a long standing interest in Egfr Cytomegalic are seminal publication of the first.

Sean A. McCarthy: However, successful antibody masking was focused on.

Sean A. McCarthy: On the Egfr binding antibody cetuximab, but which we showed a marked reduction in systemic skin rash for the masked antibody compared to the unmasked version.

Sean A. McCarthy: These findings set the stage for the evolution of the mono specific egfr probe already into our CX 904 bi specific T cell engagements. We reason that Egfr is a target has so much more potential to be realized.

Sean A. McCarthy: We reason that EGFR as a target has so much more potential to be realized, and the realization of this potential would require a more potent effector mechanism, leading us to the concept of the MAF EGFR CD3 strategy encompassed in CX904. We did actually publish an early lead molecule from this program in cancer research to demonstrate preclinical proof of concept, and we subsequently refined the structure using the depth of our platform and in collaboration with our partner Amgen. The next slide shows the molecular architecture of 904. CX904 has one CD3 binding domain and one EGFR binding domain. Both domains are masked by unique peptides.

Sean A. McCarthy: The realization of this potential would require a more potent effective mechanism leading us to the concept of the mass Egfr CD three strategy encompassed in CX 904, we did actually publish an early lead molecule from this program in cancer research to demonstrate preclinical proof of concept and we subsequently refined this structure using the depth of our plan.

Sean A. McCarthy: Furthermore, the protease-cleavable substrates are different in each binding domain, reflecting our preclinical fine-tuning strategy for optimization of the therapeutic window. CX904 also has an FC region, and so it would be expected to have an antibody-like half-life. This overall structure is somewhat similar to Amgen's tarlatumab, which has shown impressive results in small cell lung cancer. Shown on the right of this slide is a recap of the therapeutic concept for CX904 and for our platform generally. The concept is that masking reduces drug binding to targets in normal tissues, whereas in tumor tissues, the masks are removed by activated tumor protease.

Sean A. McCarthy: Form and in collaboration with our partner Amgen.

Sean A. McCarthy: The next slide shows the molecular architecture of 904.

Sean A. McCarthy: 904 has one CD three binding domain and one egfr binding domain. Both domains are masked with unique pet sites. Furthermore, the protease cleavable substrates are different at each binding domain, reflecting our preclinical fine tuning strategy for optimization of therapeutic window.

Sean A. McCarthy: <unk> also has an FC region and so it would be expected to have an antibody like half life.

Sean A. McCarthy: This overall structure is somewhat similar to amgen's Todd aftermath.

Sean A. McCarthy: Impressive results in small cell lung cancer.

Sean A. McCarthy: Shown on the right of this slide is a recap of the therapeutic concept for CX 904 and for our platform generally.

Sean A. McCarthy: The concept is that marketing reduces drug binding to target in normal tissues, whereas in tumor tissue the Moscow removed by activated tumor proteases.

Sean A. McCarthy: This tumor localization leads to the improvement or creation of a therapeutic window. For the EGFR-CD3 antigen pair, it has been shown previously that the unmarked bispecific is highly toxic in preclinical models. So our masking strategy is, we believe, essential for creating a therapeutic window.

Sean A. McCarthy: <unk> localization lease that the improvement or creation of a therapeutic window.

Sean A. McCarthy: For the Egfr CD three adds to impair its been shown previously that the unmarked by specific is highly toxic in preclinical models. So our marketing strategy is we believe essentials, we're creating a therapeutic window.

Sean A. McCarthy: In terms of the toxicities we're looking to mitigate, EGFR antibodies are well known to cause rash and gastrointestinal side effects. And so we've been specifically looking out for our masking strategy to really limit serious EGFR toxicities, particularly grade three and above. With regard to CD3, our masking strategy is, of course, designed to limit CRS and ICAM.

Sean A. McCarthy: In terms of the toxicities were looking to mitigate egfr antibodies are well known to cause rash and gastrointestinal side effects.

Sean A. McCarthy: Specifically looking at looking at for our masking strategy to really limit Sirius Egfr toxicities, particularly grade three and above with regard to CD three I'm asking strategy is of course designed to limit Crs and icons.

Sean A. McCarthy: Okay.

Sean A. McCarthy: Before handing over to Wayne, let me review the high-level goals and achievements to date for our Phase 1 study of CX904. Given the really high potency of T cell engagement and the widespread expression of EGFR, goal number one for this study has been to evaluate the safety of 904, and we've made excellent progress, as you will see from Wayne's presentation. We've explored non-STEP and STEP dosing. We were very pleased to see very limited CRS with non-STEP dosing, we believe because of successful CD3 masking, and in step dosing cohorts, rather remarkably, we've seen no CRS at all. We've also seen no evidence of ICANNs at any dose level or schedule.

Sean A. McCarthy: Before handing over to why wait let me review the.

Sean A. McCarthy: The high level goals and achievements to date.

Sean A. McCarthy: For our phase one study of CX 904.

Sean A. McCarthy: Given the really high potency of T cell engages and the widespread expression of Egfr goal number one for this study has been to evaluate the safety of 904, and we've made excellent progress as you will see from Wayne's presentation.

Sean A. McCarthy: We've explored non step and step dosing, we were very pleased to see very limited Crs with non step dosing, we believe because of successful CD three market.

Sean A. McCarthy: And then step dosing cohorts, rather remarkably we've seen no crs at all.

Speaker Change: We've also seen no evidence of <unk> at any dose level or schedule.

Sean A. McCarthy: Furthermore, while we have seen some EGFR toxicities, these have been manageable and have not limited us in achieving therapeutically active doses. Again, this shows the success, we believe, of our eGFR masking strategy, and this success of eGFR masking is consistent with our prior published work that I mentioned earlier. Goal number two of our phase one study has, of course, been to look for initial signs of anti-tumor activity. As we've said in recent months, any evidence of tumor stabilization or tumor shrinkage in this first-in-man study would be very encouraging.

Speaker Change: Furthermore, while we have seen some egfr toxicities. These have been manageable and have not limited us in achieving therapeutically active doses.

Sean A. McCarthy: Again. This shows the success, we believe of our Egfr marketing strategy and the success of Egfr masking is consistent with our prior published work that I mentioned earlier.

Sean A. McCarthy: Goal number two of our phase one study has of course been to look for initial signs of antitumor activity.

Sean A. McCarthy: As we've said in recent months any evidence of tumor stabilization or achieve a shrinkage. In this first demand study will be very encouraging I want to emphasize that the patient population we've enrolled.

Sean A. McCarthy: I want to emphasize that the patient population we've enrolled to date in this Phase I study is heavily pretreated with a range of tumor types and is unselected for EGFR. All that said, we're delighted to announce today very encouraging early signs of anticancer activity for 904, including confirmed resistance responses in pancreatic cancer, a very difficult to treat tumor type that is not typically responsive to eGFR inhibition or, for that matter, to immunotherapy.

Sean A. McCarthy: In this phase one study is heavily pre treated and has a range of tumor types and is unselected for egfr.

Sean A. McCarthy: All that said, we're delighted to have asked it a very encouraging early signs of anticancer activity for 904, including confirmed resist responses in pancreatic cancer, a very difficult to treat tumor type that is not typically a responsive to egfr inhibition or for that matter to immunotherapy.

Sean A. McCarthy: Moreover, our initial assessments of pharmacodynamics are supportive of the mechanism of action of CX904 as a mass T-cell engager, providing crucial platform proof of concept with read-through, we believe, to the many other programs we're working on at CytomX.

Sean A. McCarthy: Moreover, our initial assessments to pharmacodynamics are supportive of the mechanism of action of CX 904, as a mosque T cell engagement, providing crucial platform proof of concept with read through we believe to the many other programs were working on <unk>.

Wayne Chu: Importantly, this phase one study is ongoing. We're continuing to dose escalate and enroll multiple tumor types. And our next goal is to determine the recommended phase two dose and to define plans for phase one B expansion. We see the data that we're sharing today as a very promising initial step in the development of CX904, and this work positions CytomX at the forefront of the T-cell engager field. Now, I will hand over to Wayne to review the data in some detail.

Sean A. McCarthy: Importantly, this phase one study is ongoing we're continuing to dose escalate and enroll multiple tumor types, but our next goal is to determine the recommended phase II dose and to define plans for phase one expansions.

Wayne Chu: We see the data that we're sharing today as a very promising initial step in the development of CX 904, and this work positions <unk> at the forefront of the T cell engage a field now let me hand over to Wayne to review the data in some detail.

Wayne Chu: Thanks, Sean, and thanks, everyone, for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study. This slide summarizes the dose escalation scheme, key eligibility criteria, and study objectives. Patients with tumors with no EGFR expression were enrolled.

Wayne Chu: Thanks, Shawn and thanks, everyone for the opportunity to share our early clinical and translational observation in the ongoing dose escalation study.

Wayne Chu: This slide summarizes the dose escalation scheme key eligibility criteria and the study objectives.

Wayne Chu: Patients with tumors with known Egfr expression, where enroll however patients were not selected based on Egfr expression.

Wayne Chu: However, patients were not selected based on EGFR expression. Dose escalation was initiated using a non-step dosing schedule in which CX904 was dosed once every two weeks; doses starting from 7 micrograms through 6 milligrams were tested. As we will discuss in the subsequent slides, dose escalation of CX904 continued using a step-dosing schedule with an initial target dose of 5 millibars. Various step-dosing schedules were tested, after which the target dose was administered every two weeks.

Wayne Chu: Dose escalation was initiated using a non step dosing schedule and which CX 904 was dosed once every two weeks.

Wayne Chu: Doses, starting from seven micrograms through six milligrams were tested.

Wayne Chu: We will discuss in the subsequent slide dose escalation of CX 904 continued using a step dosing schedule with an initial target dose of five milligrams.

Wayne Chu: Various step dosing schedules were tested after which the target dose was administered every two weeks.

Wayne Chu: The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose. And, as Sean mentioned, dose escalation continues with the current enrollment testing the 15 milligram target dose. Selected baseline characteristics for enrolled patients are shown in this slide. The majority of patients enrolled in non-step dosing escalation cohorts were those with microsatellite-stable or MSS colorectal cancer, which I will call Perm CRC from here on out, which has been demonstrated to be unresponsive to immune therapies such as checkpoint inhibitors.

Wayne Chu: The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose.

Wayne Chu: And as Sean mentioned dose escalation continues with the current enrollment testing the 15 milligram target dose.

Wayne Chu: Selected baseline characteristics for enrolled patients are shown in this slide.

Wayne Chu: The majority of patients enrolled in non step dosing escalation cohorts, where those with microsatellite stable or MSS colorectal cancer, which I will term CRC from here on out which has been demonstrated to be unresponsive to immune therapies, such as checkpoint inhibitors.

Wayne Chu: With step dose escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity, as well as other tumor types with no EGFR expression. As is typical for a Phase I first-in-human dose escalation study, patients had advanced late-line disease. Enrolled patients received a median of four prior cancer therapies, many were refractory to their last prior therapy, and a considerable proportion received prior EGFR therapy and or PD-1 and PD-L1-directed therapy. Early clinical pharmacokinetic data from the non-step dosing schedule were consistent with the CX904 ProBody T-Cell Engager design.

Wayne Chu: With snap dosing with step dosing escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity as well as other tumor types with known Egfr expression.

Wayne Chu: As is typical for a phase one first in human dose escalation study patients had advanced late line disease.

Wayne Chu: All patients received a median of four prior cancer therapies. Many were refractory to their last prior therapy and a considerable proportion received prior egfr <unk>, our PD, one and PD lone directed therapy.

Wayne Chu: Yeah.

Wayne Chu: Early clinical pharmacokinetic data from the non step dosing schedule was consistent with the CX 904 pro body T cell engagement design. The graph on the left shows that total CX 904 exposure increases linearly with increasing dose, indicating no apparent change in dose dependent clearance or evidence of <unk>.

Wayne Chu: The graph on the left shows that total CX904 exposure increases linearly with increasing dose, indicating no apparent change in dose-dependent clearance or evidence of target-mediated drug disposition. The graph on the right shows the cycle 1 PK profile of CX904 at the 3 milligram dose level. The three curves show circulating analyte concentrations of intact or masked CD3, intact EGFR, and total probiotic. Notably, the three curves are essentially superimposable, indicating that CX904 exists in circulation in predominantly intact, or matched, form. Preliminary estimates of CX904's half-life are between 2.8 and 5.3 days.

Wayne Chu: Target mediated drug disposition.

Wayne Chu: The graph on the right shows the cycle, one PK profile of CX 904 at the three milligram dose level. The three curves showed circulating analyte concentrations of intact, our math CD three <unk> Egfr and total pro body, notably the three curves are essentially superb.

Wayne Chu: Causal, indicating that CX 904 exists in circulation and predominantly intact or mast form.

Wayne Chu: Preliminary estimates of CX 904, half-light are between two 8% and five three days.

Wayne Chu: This slide summarizes treatment-related adverse events observed with CX904 in the non-step dosing schedule. It is important to mention that during the CX904 escalation, no corticosteroids or other prophylactic medication was administered for systemic toxicity such as CRS and IQ. The safety and tolerability data shown here with non-step dosing therefore reflect the ability of the masking to mitigate CRS and IQ. Considering that, the virtual absence of CRS and ICANNs is quite striking.

Wayne Chu: This slide summarizes treatment related adverse events observed with CX 904, and the non step dosing schedule.

Wayne Chu: It is important to mention that during the CX 904 escalation no corticosteroids or other prophylactic medication was administered for systemic toxicities, such as Crs and <unk>.

Wayne Chu: The safety and Tolerability data shown here with non step dosing, therefore reflect the ability of the masking to mitigate Crs and ICANN.

Wayne Chu: With that the virtual absence of Crs and I cant is quite striking during the.

Wayne Chu: Through the 3 mg dose level, no CRS or ICANs of any grade were observed. Even at the 6 mg dose level, where two patients had dose-limiting toxicity of grade 3 tinnitinovitis and grade 3 rash, no patients experienced ICANNs of any grade, and only grade 1 CRS, characterized by transient fever without any other signs or symptoms associated with CRS, was observed. Low-grade musculoskeletal adverse events such as arthralgia and arthritis were observed, in addition to one grade three tenosynovitis at the six milligram dose level.

Wayne Chu: Three milligram dose level, no crs or <unk> hands of any grade were observed.

Wayne Chu: Even at the six milligram dose level, where two patients had dose limiting toxicity of grade III tennis, synovitis and great III rash no patients experienced I can't have any grade and only grade one crs characterized by transient fever without any other signs or symptoms associated with Crs.

Wayne Chu: <unk> observed.

Wayne Chu: Low grade musculoskeletal adverse events, such as our <unk> and arthritis were observed in addition to the one great three tenets synovitis added six milligram dose level.

Wayne Chu: Musculoskeletal events overall appear to be associated with a dose-dependent increase in circulating IL-6, as shown in the graph. This is in direct contrast with CRS, where the association with circulating IL-6 levels was much less evident. Similarly, except for the grade 3 rash observed at the 6 milligram dose level, only grade 1 rash was observed. Overall, the data presented here quite convincingly demonstrate the benefit of masking on effectively eliminating CRS and ICANs, which constitute dose-limiting toxicities with high T cell engagement.

Wayne Chu: Let's skeletal events overall appear to be associated with a dose dependent increase in circulating IL six as shown in the graph. This is in direct contrast with Crs.

Wayne Chu: Where are the association with circulating IL six levels with much less evident.

Wayne Chu: Similarly, except for that great III rash observed at the six milligram dose level only grade one rash was observed.

Wayne Chu: Overall, the data presented here quite convincingly demonstrate the benefit of masking on effectively eliminating <unk> and ICANN, which constitute dose limiting toxicity with many T cell engagements.

Wayne Chu: Based on the observations during dose escalation on the non-STEP dosing schedule, which demonstrated that CRS and ICANs are effectively mitigated by the masking of CX904, STEP dosing schedules and tocilizumab prophylaxis were used specifically to mitigate emerging musculoskeletal adverse events, maintain a broad therapeutic index, and allow continuation of escalation to higher and potentially more efficacious target dose These measures enabled escalation to higher CX904 target doses while continuing to maintain an acceptable safety and tolerability profile. Impressively, no CRS or ICAN of any grade was observed.

Wayne Chu: Based on the observations during dose escalation on the non step dosing schedule, which demonstrated that Crs and I cant are effectively mitigated by the masking of CX 904 step dosing schedules and towards the Loopnet prophylaxis, where you'd specifically to mitigate emerging muscular skeletal adverse events, Maine.

Wayne Chu: <unk> broad therapeutic index and allow continuation of escalation to higher and potentially more efficacious target doses.

Wayne Chu: These measures enabled escalation to higher CX 904 target doses, while continuing to maintain an acceptable safety and tolerability profile.

Wayne Chu: Preferably no crs or I can stop any grade was observed. Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX 904 target doses no related grade three rash its were reported and no treatment related adverse events resulted in CX 904.

Wayne Chu: Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX904 target doses, no related grade 3 rashes were reported, and no treatment-related adverse events resulted in CX904 treatment discontinuation. Overall, the safety profile of CX904 continues to be favorable and importantly enables CX904 administration and management of adverse events in an outpatient setting. In this regard, per protocol, no mandatory hospitalization is required for monitoring at clear dose levels, and the safety profile observed to date has not necessitated a change to this practice.

Wayne Chu: Discontinuation.

Wayne Chu: Overall, the safety profile of CX 904 continues to be favorable and importantly enables CX 904 administration and management of adverse events in an outpatient setting and.

Wayne Chu: In this regard per protocol no mandatory hospitalization is required for monitoring a clearer dose levels and the safety profile observed to date has not necessitated a change to this practice.

Wayne Chu: In the context of a favorable safety profile, we observed compelling signs of CX904 anti-tumor activity, highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma. The responses observed with CS904 are highly encouraging, given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely poor with current available therapy. Shown here is the waterfall plot of six efficacy-evaluable patients treated across a range of target doses on both non-STEP and STEP dosing schedules. Confirmed partial responses per RESIST 1.1 criteria were observed in two of the six patients.

Wayne Chu: In the context of a favorable safety profile, we observed compelling signs of CX 904, anti tumor activity highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma <unk>.

Wayne Chu: One was treated with six milligrams on a non-step dosing schedule and had an 83% reduction in measurable tumor burden, and a second patient was treated on a step dosing schedule with a target dose of five milligrams and had a 51% reduction in tumor burden. Furthermore, of note, all six patients have disease control. Of the six patients, two remain on study treatment, and we will now discuss these patients in greater detail. The first case describes a confirmed partial response in a 49-year-old patient with metastatic pancreatic adenocarcinoma.

Wayne Chu: The responses observed with CX sign up or are highly encouraging given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely quarter with current available therapies.

Wayne Chu: Here is the waterfall plot of six efficacy evaluable patients treated across a range of target doses on both non step in step dosing schedules.

Wayne Chu: Confirmed partial responses per resist one one criteria were observed in two of the six patients one was treated with six milligrams on a non stop dosing schedule and had an 83% reduction in measurable tumor burden and a second patient was treated on a step dosing schedule with a target dose of five milligrams and had a 51.

Wayne Chu: 1% reduction in tumor burden.

Wayne Chu: Furthermore of note all six patients.

Wayne Chu: Had disease control.

Wayne Chu: Of the six patients to remain on study treatment and we will now discuss these patients in greater detail.

Wayne Chu: Prior therapies included surgery, radiation therapy, and three lines of prior chemotherapy. The patient received CX904 on a step-dosing schedule with 1.5 milligrams administered on day one, and the target dose of 5 milligrams administered one week later and then two weeks thereafter every two weeks thereafter. The patient did not experience cytokine relief syndrome or ICANS. The patient experienced grade three related arthralgia, but this resolved to grade one after a one cycle delay in the administration of corticosteroids.

Wayne Chu: The first case described a confirmed partial response and a 49 year old patient with metastatic pancreatic adenocarcinoma. Prior therapy included surgery radiation therapy, and three lines of prior chemotherapy to.

Wayne Chu: The patient received CX 904 on a step dosing schedule with one five milligrams administered on day, one and the target dose of five milligrams administered one week later and then two weeks thereafter every two weeks thereafter.

Wayne Chu: The patient did not experienced cytokine release syndrome or <unk>, the patient experienced grade three related arthralgia, but this result, the great. One after one cycle delay and administration and corticosteroids at.

Wayne Chu: As shown in the CET scan images the patient achieved a partial response.

Wayne Chu: With deeper reduction in tumor burden to serve as the confirmatory scan and as I mentioned and this patient remains on CX 904 treatment, having received over three months of treatment to date.

Wayne Chu: As shown in the CT scan images, the patient achieved a partial response, with a deeper reduction in tumor burden observed at the confirmatory CT scan. And as I mentioned, this patient remains on CX904 treatment, having received over three months of treatment to date. This next case illustrates durable, stable disease with CX904 in a 59-year-old patient with metastatic pancreatic adenocarcinoma who had received three prior lines of systemic chemotherapy. The patient received CX904 on a step-dosing schedule with 1.5 milligrams administered on day 1, 5 milligrams on day 8, and 10 milligrams on day 15 every two weeks thereafter. The patient tolerated CX904 treatment well, with no CRS, ICANs, or musculoskeletal events and only grade one papulopustular rash, which resolves with topical treatment.

Wayne Chu: This next case illustrates durable stable disease with CX 904, and a 59 year old patient with metastatic pancreatic adenocarcinoma, who had received three prior lines of systemic chemotherapy.

Wayne Chu: The patient receives CX 904 on a step dosing schedule with one five milligrams administered on day, one five milligrams on day, eight and 10 milligrams on day 15 every two weeks thereafter.

Wayne Chu: Patient tolerated CX 904 treatment well with notes Crs I can or muscular skeletal events.

Wayne Chu: And only great one Papua pustular, rash, which resolved with topical treatment.

Wayne Chu: The patient was able to maintain stable disease with no evidence of measurable tumor growth, and additional information supporting continued clinical benefit included a greater than 50% reduction in serum CA-19 levels and overall improvement of performance status from baseline. This patient remains on CX904 treatment, having received over three and a half months of treatment to date. Preliminary translational data indicate T-cell pharmacodynamic activity that is consistent with the mechanism of action of CX904 in pancreatic adenocarcinoma.

Wayne Chu: The patient was able to maintain stable disease with no evidence of measurable tumor growth and additional information supporting continued clinical benefit included a greater than 50% reduction in CRM CA 19 levels and overall improvement of performance status from baseline.

Wayne Chu: This patient remains on CX 904 treatment, having received over three five months of treatment to date.

Wayne Chu: Preliminary translational data indicate T cell pharmacodynamic activity that is consistent with the mechanism of action of CX 904, and pancreatic adenocarcinoma.

Wayne Chu: The figure on the left is an immunofluorescent image from a biopsy obtained prior to CX904 treatment in a patient with pancreatic cancer who achieved a deep partial response. The colors indicate T-cell markers in red, dark blue, and magenta, and cancer cells in light blue.

Wayne Chu: Figure on the left is an immuno fluorescence image from a biopsy obtained prior to CX 904 treatment in.

Wayne Chu: Patients with pancreatic cancer, who achieved a deep partial response, the colors indicate T cell markers and red dark blue and magenta and cancer cells in light Blue and as you can see the pretreatment biopsies showed a high level of CDA positive T cells within the tumor microenvironment, indicating their contribution to T cell engagement anti tumor activity.

Wayne Chu: And as you can see, the pre-treatment biopsy showed a high level of CD8 positive T-cells within the tumor microenvironment, indicating their contribution to T-cell engaged anti-tumor activity. The figure on the right shows the reduction of peripheral CD8 positive T cells as it relates to the resist 1.1 response. Both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CD8 positive T cells following CX904 treatment, consistent with the trafficking of T cells from the periphery to tumor sites as a mechanism of action of T cell engagement.

Wayne Chu: <unk>.

Wayne Chu: The figure on the right shows the reduction of peripheral CDA positive T cells as it relates to resist one one response, both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CDA positive T cells. Following CX 904 treatment consistent with the trafficking of T cells from the appropriate to tool.

Wayne Chu: Site as a mechanism of action of T cell engagements.

Wayne Chu: Taking a step back from the early but compelling activity of CX904 in patients with pancreatic adenocarcinoma, shown here is the waterfall plot for efficacy-evaluable patients treated with CX904 at target doses greater than or equal to 0.75 milligrams. While no objective responses were observed in patients with other tumor types, reductions in measurable disease burden were observed in a total of eight patients, including Reductions in measurable disease burden were also observed in patients with CRC, esophageal carcinoma, and non-small cell lung cancer. We believe that the early signals of CX904 activity in pancreatic cancer are compelling and that currently tested target doses are efficacious.

Wayne Chu: Taking a step back from the early buy compelling activity of CX 904 in patients with pancreatic adenocarcinoma shown here is the waterfall plot for efficacy evaluable patients treated with <unk> for our target doses greater than or equal to <unk> 75 milligrams.

Wayne Chu: While no objective responses were observed in patients with other tumor types reductions and measurable disease burden were observed in the total of eight patients, including the two pancreatic cancer patients with partial responses reductions and measurable disease burden were also observed in patients with CRC esophageal carcinoma and non small.

Wayne Chu: Cell lung cancer.

Wayne Chu: We believe that early signals of CX 904 activity in pancreatic cancer are compelling and that currently tested target doses are efficacious.

Wayne Chu: As a result, study enrollment moving forward will focus on patients with other EGFR-positive tumor types, including lung cancer, upper GI cancers, and head and neck cancers. This slide summarizes the time-on-study treatment for patients treated with CX904, again highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit from ongoing CX904 treatment. Importantly, while CX904 has had minimal clinical activity to date in patients with CRC, it retains its pharmacodynamic activity, as illustrated in this slide, which are immunofluorescent images of biopsies taken from a patient with MSF-CRC at baseline and while on CX904 treatment.

Wayne Chu: As a result study enrollment moving forward in addition to continuing to enroll patients with pancreatic cancer will focus on patients with other egfr positive tumor types, including lung cancer upper Gi cancers in head and neck cancers.

Wayne Chu: This slide summarizes the time on study treatment for patients treated with CX 904, again, highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit with ongoing CX 904 treatment.

Wayne Chu: Importantly, while CX 904 has had minimal clinical activity to date in patients with CRC.

Wayne Chu: 904 reported pharmacodynamic activity as illustrated in this slide which are immunofluorescence images, a biopsy taken from a patient with MSS CRC at baseline and while on CX 904 treatment.

Wayne Chu: As you can clearly see at baseline, the tumor's tumor is notable for the almost complete absence of CD8 positive T cells within the tumor. In contrast, the on-treatment biopsy showed a substantial increase in the number of CD8 positive T cells within the tumor. This observation is a clear demonstration of the CX904 mechanism of action and demonstrates potential combination strategies for the treatment of CRC.

Wayne Chu: As you can clearly see at baseline the tumors tumor is notable for the almost complete absence of CDA positive T cells within the tumor and.

Wayne Chu: In contrast, the on treatment biopsy showed a substantial increase in the number of CDA positive T cells within the tumor.

Wayne Chu: This observation is a clear demonstration of the CX 904 mechanism of action and demonstrates potential combinations strategies for the treatment of CRC.

Wayne Chu: In summary, we are very encouraged by early clinical data of CX904 in the ongoing phase 1 dose escalation. CX904 has a favorable safety profile, which, given the broad expression of EGFR in normal tissues in addition to cancers, is indicative of the ability of masking to maintain a meaningful therapeutic index. Second, CX904 has promising early efficacy and pharmacodynamic activity, highlighted by the confirmed posture responses in patients with metastatic pancreatic adenocarcinoma and early demonstration of its mechanism of action, including in colorectal cancer.

Wayne Chu: In summary, we are very encouraged by this early clinical data on CX 904 in the ongoing phase one dose escalation.

Wayne Chu: <unk> has a favorable safety profile, which given the broad expression of Egfr in normal tissues. And addition to cancers is indicative of the ability of masking to maintain a meaningful therapeutic index.

Wayne Chu: Second CX 904 has promising early efficacy and pharmacodynamic activity highlighted by the confirmed partial responses in patients with metastatic pancreatic adenocarcinoma, an early demonstration of CX 904 mechanism of action, including.

Wayne Chu: Colorectal cancer.

Sean A. McCarthy: The clinical and translational observations have been extremely valuable in demonstrating not only the early clinical activity of CX904, but also provide clear direction to plants to ultimately determine the recommended phase 2 dose. This includes continued enrollment in pancreatic cancer and enrollment in other EGFR-positive tumor types that are also more responsive to immune therapies based on prior clinical experience. Together, these data will inform future development of CX904, which will include considerations of combination strategies.

Wayne Chu: The clinical and translational observations have been extremely valuable and demonstrating not only the early clinical activity of <unk>, one, but also provide clear direction to plans to ultimately determined the recommended phase II dose and this includes continued enrollment in pancreatic cancer and enrollment and other egfr positive tumor types that are also more.

Sean A. McCarthy: Responsive to immune therapies based on prior clinical experience.

Sean A. McCarthy: Together these data will inform future development of CX 904, which include consideration of combination strategies and with that I will now turn it back to Sean for concluding remarks.

Sean A. McCarthy: And with that, I will now turn it back to Sean for closing remarks. Great, thanks Wayne. So staying with CS904 for a moment, we're excited by our progress to date in developing this very novel drug candidate. EGFR is such a high potential target with expression on many tumor types, and we're just at the beginning of learning what CX904 can do for patients.

Sean: Great. Thanks Wayne.

Sean: So staying with <unk> 94 for a moment, we're excited by our progress to date developing this very novel drug candidate <unk>.

Speaker Change: <unk> is such a high potential target with expression on many tumor types and we're just at the beginning of learning what CX 904 can do for patients.

Sean A. McCarthy: We clearly have a drug candidate with confirmed monotherapy activity, and we're redoubling our efforts to generate data in additional tumor types as we more broadly explore 904. Our data also unlocks potential strategies for future combinations, as Wayne mentioned. Focusing for a moment on pancreatic cancer, this is one of the greatest areas of unmet need in oncology today, and it's notoriously difficult to treat. Second-line response rates are in the single digits, and PFS and overall survival are just a matter of months.

Sean: We clearly have a drug candidate with confirmed monotherapy activity, but we're redoubling our efforts to generate data in additional tumor types as we more broadly explore in Idaho for I'd say, it's also unlocks potential strategies for future combinations as Wayne mentioned.

Sean A. McCarthy: Focusing for a moment on pancreatic cancer. This is one of the greatest areas of unmet need in oncology today, and it's notoriously difficult to treat.

Sean A. McCarthy: Second line response rates are in the single digits.

Sean A. McCarthy: And overall survival that just a matter of months.

Sean A. McCarthy: To reiterate the importance of our data shared today, pancreatic cancer does not respond to either anti-EGFR antibodies or to immunotherapy alone. What we have shown today is that when we combine these two powerful strategies in bi-specific form, enabled by our pro-body masking technology, we can elicit meaningful responses in late-stage pancreatic cancer patients. CX904 brings these two mechanisms together into an integrated and unique pharmacology that can impact this very difficult-to-treat disease, showing how masked pro-body T cell engagers can be a new frontier in the war on cancer.

Sean A. McCarthy: To reiterate the importance of our data shared today pancreatic cancer does not respond to either anti egfr antibodies or to immunotherapy alone.

Sean A. McCarthy: What we have shown today is that when we combine these two powerful strategies and by specific form.

Sean A. McCarthy: Enabled by our priority masking technology, we can elicit meaningful responses in late stage pancreatic cancer patients.

Sean A. McCarthy: 94 brings these two mechanisms together into an integrated and unique pharmacology that could impact this very difficult to treat disease.

Sean A. McCarthy: During how most priority T cell engages could be a new frontier in the war on cancer.

Sean A. McCarthy: These results are the embodiment of exactly what CX904 was designed to do, and we plan to aggressively pursue this signal for the benefit of people afflicted with this devastating tumor type. Now, zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at CytomX. We see the data we're sharing today on 904 as a promising initial step in developing this asset and also our T-Cell Engager portfolio overall.

Sean A. McCarthy: These results are the embodiment of exactly what CX 904 was designed to do and we plan to aggressively pursue this signal for the better for the benefit of people afflicted with this devastating tumor type.

Sean A. McCarthy: Now zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at <unk>, we see the data. We're sharing today are 94 is a promising initial step in developing this asset and also our T cell engage a portfolio or.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: T-Cell Engagers are starting to break through in solid cancers, and it's exciting to be playing our part here at CytomX in this highly promising field, not only with 904, but also the many T-Cell Engager programs we're advancing through preclinical discovery and development. And we look forward to providing an additional CS904 update later this year.

Sean A. McCarthy: T cell engages our starting to breakthrough installed at Kansas, and it's exciting to be playing our part.

Sean A. McCarthy: Here at <unk> in this highly promising field not only with <unk>, but also the many T cell engaging programs, we're advancing through preclinical discovery and development and we look forward to providing an additional CX 904 updates later this year.

Sean A. McCarthy: Of course, today's update has been very 904 focused, but before I wrap up, I'd like to remind everyone to also keep our other programs in mind. We're making a lot of progress on multiple fronts. CX-2051 and CX-801 are wholly owned assets, and we anticipate phase 1a data for both in 2025.

Speaker Change: Now of course, today's update has been very 904 focus, but before I wrap up I'd like to remind everyone to also keep our other programs in mind we're.

Sean A. McCarthy: We're making a lot of progress on multiple fronts <unk> 051 in six 801, our wholly owned assets and we anticipate phase one data for both in 2025 were already in our second phase one cohort with 2051 amongst anti <unk> ADC in clinical initiation for CX 800.

Sean A. McCarthy: We're already in our second phase 1 cohort with 2051, a masked anti-Epcan ADC, and clinical initiation for CX-801, a masked interferon, is imminent. I'd like to close by thanking everyone involved in this work for their commitment to our vision. The CytomX team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer, and it's truly a privilege to work with such a talented group.

Sean A. McCarthy: One must interferon is imminent.

Sean A. McCarthy: I'd like to close by thanking everyone involved in this work for their commitment to our vision. The cytogenetics team is intensely focused on delivering an innovative pipeline for the benefit for people living with cancer and it is truly a privilege to work with such a talented team I also want to sincerely. Thank the patients who join our studies their families.

Sean A. McCarthy: I also want to sincerely thank the patients who participate in our studies, their families, and our investigators. And with that, Operator, let's go ahead and open up the call for questions. Thank you. As a reminder, to ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again.

Sean A. McCarthy: And our investigators and with that operator, let's go ahead and open up the call for questions.

Sean A. McCarthy: Thank you and as a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.

Operator: Please stand by while we compile the Q&A. And for our first question, it comes from the line of Peter Lawson from Barclays. Please go ahead. Thank you so much. Thanks for sharing the data. Really exciting.

Speaker Change: Please standby will be compile the Q&A roster.

Operator: For first question. It comes from the line of Peter Lawson from Barclays. Please go ahead.

Peter Richard Lawson: Great. Thank you so much thanks for sharing the data.

Peter Richard Lawson: Great exciting.

Peter Richard Lawson: The masking benefit you've seen, do you think that it can also extend to other T-cell engagements and then... sponsors you've seen so far? Do you think there's something special about pancreatic cancer, or do you think... get deeper responses in other, Yeah. Hi Peter.

Peter Richard Lawson: The marketing benefit you've seen do you think that can they also extend to other T cell engages and then the responses you've seen so far.

Peter Richard Lawson: Do you think is special about pancreatic cancer do you think you can get.

Peter Richard Lawson: Deeper responses and other tissues as well.

Sean A. McCarthy: Great, great questions. Thanks. Regarding the extension and the read-through to other programs, we're obviously very optimistic that that will be the case. You know, you've got to start somewhere, and 904, I think, is a very strong start for us. We've learned a lot with this one in the clinic, and as we've mentioned, both internally and with our partners, we're doing a lot of work on T-cell engagers. We have multiple programs.

Speaker Change: Yes, Hi, Peter Great great questions. Thanks.

Sean A. McCarthy: Regarding the extension and the read through to other programs. So we're obviously very optimistic that that will be the case.

Sean A. McCarthy: You've got to start somewhere and 904 I think is a very strong start for us.

Sean A. McCarthy: We've learned a lot with this one in the clinic and as we've mentioned both internally.

Sean A. McCarthy: And with our with our partners, where we're doing a lot of work in T cell engagements. We've got multiple programs in fact, the majority of our our partnered work is in T cell <unk>.

Sean A. McCarthy: In fact, the majority of our partnered work is in T-cell engagers, so we would expect to make substantial additional progress here over the next few years. In terms of pancreatic cancer, I think it's a great question. It's been interesting to see, you know, we've done a lot of thinking about this, obviously, and pancreatic is typically thought of as, you know, an immunologic cold tumor or, you know, an immunologic desert, if you like, but actually, evidence is beginning to mount suggesting that that might not be the case.

Sean A. McCarthy: Would expect to make substantial additional progress here over the next few years.

Sean A. McCarthy: In terms of the pancreatic I think it's a great question.

Sean A. McCarthy: It's been interesting to see.

Sean A. McCarthy: Yes.

Sean A. McCarthy: We've done a lot of thinking about this obviously in <unk>.

Sean A. McCarthy: Pancreatic is typically thought of as.

Sean A. McCarthy: Yes.

Sean A. McCarthy: <unk> cold tumor or.

Sean A. McCarthy: The logic desert, if you like but actually evidence is beginning to.

Sean A. McCarthy: <unk>, suggesting that that might not be the case, if you look at the Roche <unk>.

Sean A. McCarthy: If you look at the Roche BioNTech vaccine data, most recently updated at ACR, it's really interesting. It suggests that there are neoantigens in pancreatic cancer, that there is some immunologic microenvironment, and it looks like with this combination of each...well, there's also EGFR, of course, there, but no one's been able to break through with an anti-EGFR-directed therapy, so we think there could be something very unique about EGFR and CD3 in this particular tumor type, but it absolutely does We're still very early in this study. As Wayne mentioned, the problem is that the...

Sean A. McCarthy: Vaccine data most recently updated at ACR.

Sean A. McCarthy: It's really interesting that suggests that there are.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: Neo androgens in pancreatic cancer, there is some immunologic microenvironment.

Sean A. McCarthy: It looks like with this combination of each well Theres also egfr of course there.

Sean A. McCarthy: But no one's been able to breakthrough with an anti egfr directed therapies. So we think that could be something very unique about egfr CD three in this particular tumor type.

Sean A. McCarthy: But it does not indicate the others.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: Would not respond to <unk> four we're still very early in this study as Wayne mentioned the.

Sean A. McCarthy: The colorectal data is interesting. They're all MSS patients that we're showing today. That's another cold tumor.

Sean A. McCarthy: The colorectal data is interesting as Daryl MSS patients that we're showing today.

Sean A. McCarthy: That's another cold tumor.

Sean A. McCarthy: But a lot of progress has been made with T cell engages yet.

Sean A. McCarthy: CRC, so we would be looking to combination strategies there as far as the other tumor types are concerned. It's just very very early days for example, I would cite lung where we have two patients in the dose escalation study to date one of those was treated at a very low dose so probably not relevant we've already there. We just haven't done the experiment yet so we're going to keep enrolling across multiple.

Sean A. McCarthy: Not a lot of progress has been made with T-cell gauges yet in CRC, so we would be looking to combination strategies there. As far as the other tumor types are concerned, it's just very, very early days. For example, I'd cite lung, where we have two patients in the dose escalation study to date. One of those was treated at a very low dose, so probably not relevant. We just haven't done the experiment yet, so we're going to keep rolling it across multiple tumor types in Phase 1a as we continue to pursue both the pancreatic signal and define the activity of the drug across, hopefully, multiple tumor types over time. Thank you.

Sean A. McCarthy: <unk> sites in phase Iia as we.

Sean A. McCarthy: Continue to pursue both the pancreatic signal and.

Sean A. McCarthy: Define the activity of the drug across hopefully multiple tumor types over time.

Speaker Change: Great. Thank you and then the.

Sean A. McCarthy: And then the depth of the responses, is that related to EGFR expression or is it tumor mitosis? So one thing we have not shown in this presentation, but we continue to evaluate, is the level of eGFR expression as assessed by an immunohistochemistry assay. And we've been doing this on a retrospective basis for all the patients that have enrolled. To date, based on our early data with eGFR using this IHG assay, we have not seen a clear association between eGFR expression and the depth of the response.

Sean A. McCarthy: The depth of the responses is that.

Sean A. McCarthy: Correlated with Egfr expression or is it tumor microenvironment.

Sean A. McCarthy: So one thing we have not shown was shown in this presentation, but we continue to evaluate as the level of Egfr expression as assessed by immunohistochemistry assay and we've been doing it on a retrospective basis for.

Sean A. McCarthy: For all the patients that are enrolled to date.

Sean A. McCarthy: Based on our early data with Egfr by this IAC assay, we have not seen a clear association between Egfr expression and the and the depth of the response and just as an example.

Sean A. McCarthy: And just as an example, the two patients with pancreatic cancer who had a confirmed partial response; one patient had a moderately high level of eGFR expression by IHG, but the other patient had a very low level of eGFR expression.

Sean A. McCarthy: The two patients in pancreatic cancer.

Sean A. McCarthy: Who had the confirmed partial response, one patient had a moderately high level of Egfr expression by IAC, but then the but the other patient had a very low level of Egfr expression and it's actually the patient who had the 83% reduction in measurable tumor burden that has a low level of egfr expression.

Wayne Chu: And it's actually the patient who had the 83% reduction in measurable tumor burden that had the low level of eGFR expression. I think more work needs to be done there, but Peter, a lot of it depends on the assay itself, so we'll continue to look at that relationship. I'll get back into the queue, thank you so much.

Wayne Chu: Yeah.

Wayne Chu: Interesting.

Wayne Chu: I think more and more word yes, more work to be done there but.

Wayne Chu: A lot of it depends also on the assay.

Wayne Chu: So we'll continue to look at that relationship.

Speaker Change: Great I'll get back into the queue. Thank you so much.

Speaker Change: Thank you.

Peter Richard Lawson: And for the next question, it comes from the line of Roger Song from Jeffreys, please go ahead. Great, congratulations on the data, and thank you for taking our question. We have a few questions from us. The first one is related to the dose relationship.

Roger Song: And for our next question comes from the line of Roger song from Jefferies. Please go ahead.

Roger Song: Great Congrats.

Roger Song: Congrats for the data and thank you for taking my question.

Roger Song: A few questions from us.

Roger Song: First one is related to the dose relationship.

Roger Song: Since the efficacy or anti-tumor effect, [inaudible] how confident you are you can keep dosing higher. Yeah, thanks, Roger. Let me kick that one off.

Roger Song: Since the efficacy or antitumor activity is not clearly, Colorado with the dose level. My question is how do you think about as you dose higher even beyond <unk> and <unk> at the fifth seeing how do you think about the balance between the Africa.

Speaker Change: No I.

Speaker Change: I can't more.

Roger Song: Three our Egfr, Romania that.

Roger Song: Tolerability.

Roger Song: Profile.

Speaker Change: And how confident you are you can keep dosing higher thank you.

Sean A. McCarthy: You know, I say that there is a dose response in that the responses that we're seeing, the confirmed resistance responses, you know, we've seen at five and six milligrams. But remember that we began this dose escalation at seven micrograms. So, you know, the range of doses where we're seeing activity is actually really consistent with our predictions from modeling of where the biologically effective range would be. So we think we're in the zone.

Speaker Change: Yes, Thanks, Roger let me kick that one off.

Sean A. McCarthy: I would say that there is a dose response in that.

Sean A. McCarthy: The responses that were sitting in the confirmed resist responses, we've seen a five and six milligrams and remember that we began this dose escalation at seven micrograms. So.

Sean A. McCarthy: The range of doses, where we're seeing activity is actually really consistent with our.

Sean A. McCarthy: Our predictions.

Sean A. McCarthy: For modeling of whereas the biologically effective range would be so we think we're in the zone.

Sean A. McCarthy: We do believe, however, because of the safety profile, we can dose higher. Whether that will help or not, I don't think we know. I think all of us in the T cell engager field are kind of trying to figure this out. And if you look at Amgen's tarlatumab, I mean, they went all the way to 100 and concluded in the end that 10 milligrams was the dose to move forward because 100 didn't give significant additional efficacy.

Sean A. McCarthy: We do believe however, because of the safety profile.

Sean A. McCarthy: We can dose higher.

Sean A. McCarthy: Whether that will help.

Sean A. McCarthy: I don't think we know I think all of us in the T cell engage a field of trying to figure this out and if you look at Amgen's Tyler.

Sean A. McCarthy: I mean, they've got all the way to a 100.

Speaker Change: And concluded in the end at 10 milligrams was the dose to move forward because the 100 didn't give significant additional efficacy. So I think we've got to learn more but we are ready.

Sean A. McCarthy: So I think we want to learn more, but we're really very encouraged that we have this. The Clean Safety Profile with EGFR has exceeded our expectations, and it will allow us to dose escalate further, and we'll do that, and we'll see where it takes us.

Sean A. McCarthy: Very encouraged that we have this clean.

Sean A. McCarthy: Clean safety profile with Egfr.

Speaker Change: It exceeded our expectations.

Sean A. McCarthy: It will allow us to dose escalate further and we will do that and we'll see where it takes us.

Sean A. McCarthy: My follow-up question is related to your partner, Amgen. So this data, have you shared with the partner? And if so, any initial feedback?

Speaker Change: Got it.

Speaker Change: My follow up question is related to your partner Amgen. So this data have you share with.

Speaker Change: With the partner and if so any initial feedback.

Sean A. McCarthy: And also, understanding you will give a data update by the end of the year, what you are looking for in order for both of you, the two parties, to make the Phase 1B study design. Yeah, great questions. So with Anjan, let's take a little step back and talk about or just recap the agreement that we have with Amgen. So we're obviously in.

Sean A. McCarthy: Also understanding you well.

Sean A. McCarthy: Give a data update by the end of the year.

Sean A. McCarthy: What you are looking for in order for.

Sean A. McCarthy: Both of you two parties to make the phase <unk> study design.

Speaker Change: Sure.

Anjan: Yes, great questions, so with Amgen, let's take a little step back and talk about which is recap.

Sean A. McCarthy: The.

Sean A. McCarthy: The agreement that we have with Amgen. So we're obviously running the Fei.

Sean A. McCarthy: As Juan <unk> study.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: We do share data with them as it emerges.

Speaker Change: We are also responsible for running the phase one b.

Speaker Change: Once we get that up and running in the transition from phase one to phase one b. It's a decision that we will take jointly with.

Speaker Change: With Amgen and of course, the goal would be to in phase one b to enrol specific egfr positive tumor types of wastewater now quite obviously.

Sean A. McCarthy: We'll be pancreatic we would assume.

Sean A. McCarthy: We would assume based on this exciting signal that we've seen. So we, because the way that enrollment has unfolded, you know, we still have just not enrolled many patients in lung or head and neck, for example. We do want to bring in a few more patients and get some additional experience in those tumor types before we have a conversation with Amgen later in the year about what the Phase 1B strategy would be.

Speaker Change: Based on this exciting signal that we've seen.

Sean A. McCarthy: So we because we.

Sean A. McCarthy: The way that enrollment has unfolded, we still have just not enrolled many patients in lung.

Sean A. McCarthy: Our head and neck for example.

Sean A. McCarthy: Do want to bring in a few more patients get some additional experienced in those tumor types before we have the conversation with Amgen later in the year about what the phase <unk> strategy would be so the update later this year could be a couple of things that could be.

Sean A. McCarthy: So the update later this year could be a couple of things. It could be additional data from, you know, we would ballpark, we should have by the end of the year another 10 or so patients of data. It could also be an operational update, you know, that we've agreed with Amgen on the next steps. We just have to, you know, have that dialogue with them.

Sean A. McCarthy: <unk>.

Speaker Change: Additional data from that we would ballpark.

Sean A. McCarthy: We should have by end of year.

Sean A. McCarthy: 10, or so patients of data.

Sean A. McCarthy: It could also be.

Sean A. McCarthy: And operational update that we've agreed with Amgen on the next steps.

Speaker Change: We just have to.

Sean A. McCarthy: To have that dialogue.

Sean A. McCarthy: But in terms of, you know, their perspective on the data, I think that's a question best asked of them at this point in time. But obviously, we're really excited by our progress.

Sean A. McCarthy: With them, but in terms of that perspective on the data I think that's a question best asked of them at this point in time, but obviously, where we're really excited by our progress.

Sean A. McCarthy: Thank you. You're welcome. Thank you and for the next question, it comes from the line by Joe Catanzaro from Pierce Sandler.

Sean A. McCarthy: Excellent.

Sean A. McCarthy: Yes.

Sean A. McCarthy: Youre welcome.

Sean A. McCarthy: Thank you and for our next question. It comes from the line of Joe Catanzaro from Piper Sandler. Please go ahead.

Joseph Michael Catanzaro: Please go ahead. Hey, everybody, thanks for taking my questions and the exciting data here. I guess my question is, what do you think is happening? Is that some small amount getting unmasked in the periphery, or maybe a small amount getting unmasked in the tumor and then reentering circulation? And is that the tox that you're seeing?

Joseph Michael Catanzaro: Everybody. Thanks for taking my question then exciting data here I guess, maybe first one on the Egfr mediated talks that Youre seeing I guess my question is like what do you think is happening is that some small amount getting on map and periphery or maybe a small amount getting unmasking the tumor and then.

Joseph Michael Catanzaro: Re entering circulation.

Joseph Michael Catanzaro: And is that Tox that youre seeing typical sort of historical egfr experienced <unk> mab or is there anything indicative that its T cell targeting egfr on normal tissue. Thanks, and I may have one follow up.

Sean A. McCarthy: typical of sort of historical EGFR experience, say cituximab, or is there anything indicative that it's T-cell targeting of EGFR? Thanks, and I may have one follow-up. Yeah, hi Joe, thanks for the question.

Speaker Change: Yes, Hi, Jay Thanks for the question.

Sean A. McCarthy: Well, first of all, let me say that we're really, really pleased with the very low incidence of grade 3 rash in this study. We only have one patient out of 35 patients with a grade 3 treatment-related rash. That's a significant achievement, we think, because it has unlocked the opportunity to use this mechanism to shrink tumors that otherwise couldn't be shrunken with DGFR. So we're very, very pleased about

Sean A. McCarthy: The.

Speaker Change: Well first of all let me say that we're really really pleased with the very low incidence of grade three rash in this study.

Sean A. McCarthy: We have one patient over the 35 patients with grade three treatment related rash.

Sean A. McCarthy: So that's a significant achievement we think.

Sean A. McCarthy: Because it's unlocks the opportunity to use this mechanism.

Sean A. McCarthy: Sure.

Sean A. McCarthy: Otherwise couldn't be shrunk with Egfr. So we're very very pleased about that obviously early days more work to do but we're encouraged.

Sean A. McCarthy: Obviously, early days, more work to do, but we're encouraged. With any drug, you're going to see some—you're going to see A, Bs. It's very hard to say where they are coming from. Is it local?

Speaker Change: With any drug youre going to see some.

Speaker Change: Youre going to see Aes, it's very hard to say what are they where are they coming from is it local is it systemic.

Sean A. McCarthy: Is it systemic? We don't know, and we may never know, and in a way, it might not matter that much because it's all about the risk-benefit profile, and we're obviously delivering something we think we have very important here, at least initially, for patients with very late-stage pancreatic cancer. I would say— So, on the type of rash that we see, you know, cytoxamab rash is typically an acne-form rash. We are – we see some of that, you know, grade 1, grade 2. There are also, as Wayne mentioned, maculopapular rashes, which are maybe more T-cell – involve T-cells.

Speaker Change: So we don't know.

Speaker Change: We may never know.

Sean A. McCarthy: And in a way it might not matter that much because it's all about the risk benefit profile and where we're obviously delivering something we think we have very important efforts at.

Sean A. McCarthy: At least initially for patients with <unk>.

Sean A. McCarthy: Very late stage pancreatic cancer.

Speaker Change: I would say.

Sean A. McCarthy: Okay.

Sean A. McCarthy: The type of rash that we see in our Cetuximab rashes is typically the acne form rash.

Sean A. McCarthy: <unk>.

Speaker Change: We are.

Speaker Change: We see some of that grade one grade two there also.

Sean A. McCarthy: Wade mentioned Macchiato popular.

Sean A. McCarthy: Rashes, which maybe more T cell.

Sean A. McCarthy: <unk> T cells.

Sean A. McCarthy: So, I think we're going to have to learn more about it, but we're not worried about it because it's mostly grade 1, 2. In fact, across the entire study, the incidence of rash across all 35 patients was 40%, and just about all were grade 1, 2, and manageable. So, we're really encouraged by the AE profile here, not to mention the CRS profile, which really quite frankly surprised us on the upside. Yes, thanks, that's helpful.

Wade: So I think we're going to have to learn more about it but we're not worried about it because it's mostly grade one two if I had across the entire study the incidence of rash across the entire 35 patients was 40%.

Sean A. McCarthy: Just about all grade one two and manageable. So we're really encouraged by the AE profile here not to mention the Crs profile was really quite frankly surprised us to the upside.

Sean A. McCarthy: I guess maybe my follow-up for the pancreatic cancer patient that had that deep response and subsequent progression. Wondering if you could maybe elaborate a little bit more on that progression event, a new lesion, growth of a target lesion, if it was a new lesion, you're able to sort of profile it, going on. Just anything you could say there, I guess, would be... Yeah, I could provide some details on that.

Speaker Change: Yeah. Thanks, that's helpful. I guess, maybe my follow up for the pancreatic cancer patient that had that deep response then.

Speaker Change: Subsequent progression wondering if you could maybe elaborate a little bit more on that progression event.

Sean A. McCarthy: Was it a new lesion growth or a target lesion.

Sean A. McCarthy: If it was a new lesion, maybe youre able to sort of profile it and see what's going on just anything you can say there I guess would be would be interesting.

Wayne Chu: This is a patient that, you know, was treated with a six milligram non-step dose, had a confirmed partial response, that, you know, strikingly with over 80% reduction in measurable tumor burden. And the patient did progress based on growth of the target lesion from the NADER, as well as the appearance of, I think, one new target lesion.

Speaker Change: Yes, I can provide some details on that.

Wayne Chu: This is a patient that.

Wayne Chu: But for you with the six milligram.

Wayne Chu: Dosing had a confirmed partial response.

Wayne Chu: Beth.

Speaker Change: Strikingly with over 80% reduction in measurable tumor burden.

Wayne Chu: Patient that progressed based on.

Wayne Chu: The growth of the target lesion from the meter as well as the appearance of I think of one new new target lesion on non I'm, sorry, one new lesion.

Wayne Chu: Is the nature of the progression on that particular patient, but all through that.

Wayne Chu: So that was the nature of the progression in that particular patient. But all through that treatment course, the patient did quite well clinically. I mean, it was just based on the radiographic progression that we had. Okay, thanks. And maybe if I could just squeeze in one more quick one, maybe going back to an earlier question. If you could maybe speculate more on what you think is maybe going on in MSS-CRC, you know, it seems mechanistically like you're seeing T-cell infiltration, but that's not translating to tumor. Reduction

Wayne Chu: Dream of course, the patient did quite well clinically and it was just based on the radiographic progression.

Speaker Change: Okay, Thanks, and maybe if I could just squeeze in one more quick one maybe going back to an earlier question.

Speaker Change: Maybe speculate more on what you think it may be going on in MSS CRC.

Speaker Change: Seen mechanistically like Youre seeing T cell infiltration, but that's not translating to tumor.

Sean A. McCarthy: So I'm wondering if you have any other sort of hypotheses of what may be going on in in those patients. Thanks. I think mechanistically, it's really interesting.

Speaker Change: Reduction so I'm wondering if you have any other sort of hypotheses of what may be going on in there.

Speaker Change: Those patients.

Sean A. McCarthy: When we think about how T cell engagement works overall, right, the CD3, CD3 combined with a tumor antigen, you know, we think of these typically as being MHC nonrestricted mechanisms. That may very well be what's going on, but there could be more that's necessary to really mount an anti-tumor response. I think we're, you know, again, in the field. I think there's more to be learned about specifically how CD3 T cell engagers kill cancer cells, although clearly, we're doing it in pancreatic cancer. We're getting the T cells there in CRC, but it draws one's attention to think about what combination strategies could get you to the actual objective, you know, tumor responses.

Speaker Change: I think mechanistically, it's really interesting.

Sean A. McCarthy: When we think about how T cell engages work overall CD three.

Sean A. McCarthy: CD three combined with a tumor antigen.

Sean A. McCarthy: We think that these typically as being MHC nonrestricted mechanisms that may very well very well, what's going on but that could be that could be more than necessary severity masonite tumor response, I think we're again in the field I think theres more to be.

Sean A. McCarthy: Learned about specifically, how CD three T cell engages kill cancer cells.

Sean A. McCarthy: We're doing it in pancreatic cancer, where getting the T cells there in CRC.

Sean A. McCarthy: It draws attention to thinking about what combination strategies could get you to actual objective tumor responses. So I think more work to do there and some of the basic science.

Sean A. McCarthy: And then also clinical work that we can do.

Sean A. McCarthy: In terms of clinical combinations.

Speaker Change: Quite intriguing.

Speaker Change: Okay. Okay. Thanks, Thanks for the update and thanks for taking my question.

Speaker Change: You bet.

Sean A. McCarthy: So, I think more work to do there in some of the basic science and then also clinical work that we can do in terms of clinical combinations is quite intriguing. Thanks for the update and thanks for taking my question. Thank you. And for your next question, it comes from Delilah Edzard-Darao from BMO Capital Markets. Please go ahead.

Speaker Change: Thank you and for your next question comes from July of <unk> <unk> from BMO capital markets. Please go ahead.

Etzer Darout: Thanks for taking the question. Just wondering if you could maybe talk through your current thoughts on sort of the step versus the non-step dosing, particularly in the pancreatic patients that sort of had the response, and how you're kind of thinking about potentially moving one or the other option forward as you sort of expand the patients. And then I don't know if you said this specifically, but about sort of the EGFR expressions across the patients that you've seen so far.

Delilah Edzard-Darao: Great. Thanks for taking the question just wondering if you could maybe talk through your current thoughts on sort of the.

Etzer Darout: The step versus the non stop dosing, particularly in the pancreatic.

Etzer Darout: Patients that sort of had to response and how you're kind of thinking about potentially moving one or the other option forward as you sort of expand the patient and then.

Etzer Darout: Don't know if you said this specifically but.

Etzer Darout: About sort of the egfr expressions across sort of the patients.

Etzer Darout: Is it that you're going to, moving forward, look at EGFR expressions? Or is there an opportunity to kind of look at EGFR expressions across the folks that you've already sort of enrolled in the study? I don't know if I caught that correctly.

Speaker Change: That you've seen so far is it that youre going to moving forward you will look at Egfr expression or is there an opportunity to kind of look at egfr expression across the folks that you've already sort of enrolled in the study I don't know if I caught that correctly. Thank you.

Sean A. McCarthy: Thank you. Yeah, thanks. Thanks, Ed, sir.

Speaker Change: Yes. Thanks.

Speaker Change: In terms of moving forward with Stefan non stack, we obviously havent made a decision on that yet, but I would say.

Sean A. McCarthy: Based on our experience to date.

Sean A. McCarthy: More likely that our phase one b doses will be set.

Sean A. McCarthy: Strategies.

Sean A. McCarthy: Because it's allowing us to get to significantly higher target doses.

Sean A. McCarthy: We do think there's a dose response here.

Sean A. McCarthy: Of sorts.

Sean A. McCarthy: So.

Speaker Change: More to be learned there.

Speaker Change: Sure.

Speaker Change: We will also likely take.

Sean A. McCarthy: When you think about project Optimus considerations will likely want to take more than one dose.

Sean A. McCarthy: In terms of, you know, moving forward with step or non-step, we obviously haven't made a decision on that yet, but I would say, based on our experience to date, that it's more likely that our phase 1B doses will be step strategies because it's allowing us to get to significantly higher target doses. And we do think there's a dose response here of sorts, you know, so more to be learned there We'll also likely take it.

Sean A. McCarthy: Schedule into phase <unk>.

Speaker Change: <unk> further experience of.

Sean A. McCarthy: The drug candidate.

Sean A. McCarthy: Not only in pancreatic but also in other in other tumors as well.

Sean A. McCarthy: When you think about project optimist considerations, we'll likely want to take more than one dose and schedule it into phase 1b to gain further experience of the drug candidate, not only in pancreatic cancer but also in other tumors as well. In terms of EGFR, it's surprising, actually, how the available assay for EGFR, or assays for EGFR by IHC, let's just say they're not perfect, and so we're not sure how much one would want to rely on them moving forward, particularly because it doesn't seem from our early data that this is a straightforward ADC type thing where a high target is required for activity.

Sean A. McCarthy: In terms of Egfr.

Sean A. McCarthy: It's surprising actually how.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: How should I put this.

Sean A. McCarthy: The available assay for Egfr assays for Egfr by IAC, Let's just say, it's not perfect and so we're not sure how much one would want to rollout it moving forward, particularly because it doesn't seem from our early data.

Sean A. McCarthy: As a straightforward.

Sean A. McCarthy: ADC type thing, where you high target is required for activity, yes. These drug drugs like T cell engages.

Sean A. McCarthy: You know, these drugs like T cell engages would be predicted to be active at low target levels because of the mechanism of, you know, the amplified mechanism of tumor killing where one T cell can kill multiple tumor cells. I think we've got more to learn there, and that's why we may not be needing or leveraging eGFR selection on a go-forward basis based on what we've seen so far.

Speaker Change: <unk> would be predicted to be active at low target levels.

Sean A. McCarthy: Because of the mechanism of <unk>.

Sean A. McCarthy: The amplified mechanism of tumor, killing T cells can kill multiple tumor cells. So.

Sean A. McCarthy: I think we've got more to learn there.

Speaker Change: That's why we're where.

Sean A. McCarthy: We may not be.

Sean A. McCarthy: Needing or leveraging Egfr selection on a go forward basis based on what we've seen so far.

Speaker Change: Got it thank you.

Speaker Change: Youre welcome.

Speaker Change: One moment for your next question.

Sean A. McCarthy: Thank you. You're welcome. One moment for the next question. And for our next question, it comes from the line of Anupam Rama from J.P. Morgan. Please go ahead. Hey guys, how are you?

Sean A. McCarthy: And for our next question comes from the line of <unk> Rama from Jpmorgan. Please go ahead.

Anupam Rama: Thanks so much for the data update. Can you comment? Was there anything in the baseline characteristics, number of prior treatments? I think the PDAC case study that you said was three lines of therapy or otherwise that might be predictive of a response. I think based on the first question, EGFR expression did correlate.

Rama: Hey, guys. How are you. Thanks, so much for the data update.

Anupam Rama: Can you comment.

Anupam Rama: Is there anything in the baseline characteristics number of prior treatments I think the case study that you said was three lines of therapy or otherwise that might be predictive of response I think based on the first question Egfr expression didn't correlate and then can you comment and I'm, sorry, if I missed that.

Sean A. McCarthy: And then can you comment, and I'm sorry if I missed this. The other three stable disease patients? What was their duration?

Sean A. McCarthy: The other three stable disease patients.

Rama: What was their duration. Thanks, so much.

Sean A. McCarthy: Thanks Anupam. I'll take the first question in terms of, you know, which I think was editing out patient characteristics that could have been predictive of response. And I'd say, no, not really.

Sean A. McCarthy: Thanks.

Speaker Change: I'll take the first question in terms of.

Sean A. McCarthy: Yeah.

Speaker Change: Which I think was with anything in the patient characteristics that could be predictive of response in I would say no not really.

Sean A. McCarthy: Again, these are all pretty late-line patients, and aside from EGFR, Yeah, we did show, that said, Wayne showed a slide of a pretreatment biopsy of a patient with pretty high levels of pretreatment CD8-positive cytotoxic T cells, which is intriguing and certainly could have contributed to the response. And so that's something that we have observed.

Sean A. McCarthy: Again these are all pretty late line patients and.

Sean A. McCarthy: Aside from Egfr.

Speaker Change: Yes, we did show.

Sean A. McCarthy: That said <unk> showed a slide.

Sean A. McCarthy: <unk>.

Sean A. McCarthy: Our pre treatment biopsy of a patient with pretty high levels of pre treatment.

Sean A. McCarthy: Positive cytotoxic T cells, which.

Sean A. McCarthy: Which is intriguing.

Sean A. McCarthy: Right.

Rama: And certainly could have contributed to the response and so.

Sean A. McCarthy: That's something that we have observed we don't have that data systematically across the whole study that's difficult data to get.

Sean A. McCarthy: We don't have that data systematically across the whole study. That's difficult data to get for every patient, but it is intriguing. In terms of stable disease, Wayne can address that question real quick. Yeah, so as we, you know, showed in the swim lane plot during the presentation, there were a number of patients who were able to maintain stable disease through at least one tumor response. And, you know, smattering that included a smattering of patients that had durable, stable disease through tumor, two tumor responses. But for, otherwise, patients were able to achieve stable disease. And then it was followed by progressive disease.

Wayne Chu: For every patient, but it is intriguing.

Sean A. McCarthy: <unk>.

Wayne Chu: In terms of the stable disease.

Sean A. McCarthy: Wayne can address that question real quick.

Wayne Chu: So as we are.

Wayne Chu: Showed in the swim lane plot during our presentation.

Wayne Chu: There were a number of patients who were able to maintain a stable disease for at least one.

Wayne Chu: Tumor response.

Wayne Chu: Smattering that include a smattering of patient that had durable stable disease through tumor to tumor responses, but otherwise.

Wayne Chu: Otherwise patients were able to achieve it.

Speaker Change: <unk> disease.

Speaker Change: And then it was followed by progressive disease.

Wayne Chu: I do think it's important to reemphasize that, you know, these, these, again, the pancreatics are very, as everyone knows, it's a very rapidly progressing disease. These, these are patients who, for the most part, have had, you know, three or four prior surgeries. And so, you know, this, this, So, yeah, we think this is really exciting data. Thanks so much for taking our questions. Thank you, and as a reminder, to ask a question, simply press star 1 1 on your telephone keypad. And for the next question, it comes from the line of Mitchell Kapoor from HFC Wainwright.

Wayne Chu: I do think it's important to reemphasize that again.

Mitchell Swaroop Kapoor: Again, the pancreatic is a very as everyone knows it's a very rapidly progressing disease. These are patients who for the most part have had three or four priors and so.

Wayne Chu: This.

Mitchell Swaroop Kapoor: So we think this is a very exciting data.

Mitchell Swaroop Kapoor: Thanks, so much for taking our questions.

Mitchell Swaroop Kapoor: Thank you and as a reminder to ask a question simply press star one on your telephone keypad.

Wayne Chu: For our next question comes from the line of Mitchell Kapoor from HFC Wainright. Please go ahead.

Mitchell Swaroop Kapoor: Please go ahead. Hi everyone, congrats on the positive data. I wanted to ask about the total eight patients with tumor reductions. The others, well, I guess if you could just broadly comment on what a spider plot for these patients might look like. Are you seeing a trend in depth of response over time? Or how are we seeing those tumor reductions evolve? Yeah, I mean, it's early days.

Mitchell Swaroop Kapoor: Hi, everyone. Congrats on the positive data.

Mitchell Swaroop Kapoor: Wanted to ask.

Mitchell Swaroop Kapoor: The <unk>.

Mitchell Swaroop Kapoor: Total eight patients with tumor reductions.

Mitchell Swaroop Kapoor: Others, well I guess, if you could just broadly comment on what a spider plot for these patients might look like are you seeing a trend in depth of response over time or how are we seeing those tumor reductions evolves.

Sean A. McCarthy: I think that those eight patients, obviously two of them are the pancreatic patients, you can see them in the waterfall plot. I think there's encouragement there in terms of the fact that escalation continues, we'll keep pushing the dose here. So, you know, at this point, I think it's fair to say the spider plot will be relatively immature.

Speaker Change: Yes, I mean, it's early days I think those that those eight patients deteriorate over the pancreatic patients and you can see them in the vertical block.

Sean A. McCarthy: I think there is encouragement there in terms of the fact that escalation continues we'll keep pushing the dose here.

Sean A. McCarthy: So at this point I think it's fair to say despite of what will be relatively immature.

Speaker Change: Okay. Thank you and.

Wayne Chu: Okay, thank you. And could you just comment on the other confirmed partial response patient and how much duration of follow-up that patient had? That patient, again, was treated at the 6 milligram non-step dosing schedule, had confirmed partial response, and that patient remained on study treatment for approximately 18 weeks before experiencing progressive disease. Okay, great. Thank you for taking my questions. You're welcome. Thank you, and I'm showing no further questions. I would now like to turn the conference back to Dr. Sean McCarty, CytomX's Chairman and CEO, for a closing remarks.

Wayne Chu: Could you just comment on the other confirmed partial response patient and how much duration of follow up that patient.

Wayne Chu: So that patient.

Wayne Chu: One was treated at the six milligram non step dosing schedule had confirmed partial response and that patient remained on study about eight on study treatment of cockpit, the 18 weeks before having progressive disease.

Speaker Change: Okay, great. Thank you for taking my questions.

Speaker Change: Youre welcome.

Sean A. McCarthy: Thank you and I'm showing no further questions I would now like to turn the conference back to Dr. Sean Mccarthy Si Thomasas, chairman and CEO for closing remarks.

Wayne Chu: Great, thank you very much. And thank you everyone for listening in today. CytomX has made terrific progress so far in 2024, and we look forward to providing additional updates as the year progresses and as we continue to build our company for the long term to make the biggest difference we can for patients.

Sean A. McCarthy: Great. Thank you very much and thanks, everyone for listening in today.

Sean A. McCarthy: This has made terrific progress so far in 2024, and we look forward to providing additional updates as the year proceeds and as we continue to build our company for the long term to make the biggest difference we can.

Sean A. McCarthy: And so, thank you very much. Have a good evening. This concludes today's conference call. Thank you for participating, and you may now disconnect.

Wayne Chu: For patients and so thank you very much have a good evening.

Sean A. McCarthy: This concludes today's conference call. Thank you for participating and you may now disconnect.