Q2 2024 CytomX Therapeutics Inc Earnings Call

August 8, 2024

Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics second quarter 2024 financial results call. Please be advised that today's call is being recorded. I would now like to hand the call over to your host for today, Chris Ogden, CytomX's chief financial officer. Please go ahead.

Unknown Executive: 24 Financial Results Call. Please be aware that today's call is being recorded.

Unknown Executive: Financial Results Call. Please be advised that today's call is being recorded. I will now turn the call over to your host for today, Chris Ogden, CytomX's Chief Financial Officer.

Unknown Executive: I want to kind of call the call over to your host for today, Chris Ogden, CytomX's Chief Financial Officer. Please go ahead.

Christopher Ogden: Thank you. Good afternoon. And thank you for joining us.

Christopher 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. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov.

Christopher Ogden: Before we begin, I would like to remind everyone that during this call, we will be making four looking statements because four looking statements relate to the future. They are subject to inherent uncertainty. These and risks, they're difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public violence with the SEC at SEC.gov. We undertake no obligations to update any four looking statements, whether as a result of new information, future developments, or otherwise.

Chris Ogden: Thank you. Good afternoon, and thank you for joining us.

Speaker Change: Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent certainties and risks, they are difficult to predict, and many of which are outside of our

Important risks and uncertainties are set forth in our most recent public violence with the SEC at SEC.gov.

Christopher Ogden: We undertake no obligations to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our second quarter 2024 financial results and highlights recent progress at CytomX. We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, the press release, the recording of this call, and our SEC filings can be found under the Investors and News section of our website.

Speaker Change: We undertake no obligations to update any forelooking statements, whether as a result of new information, future developments, or otherwise.

Christopher Ogden: Earlier this afternoon, we issued a press release that includes the summary of our second quarter 2024 financial results and highly treason progress at PhytomX. We encourage everyone to read today's press release in the associated materials, which have been filed with the SEC. Additionally, the press release, recording of this call, and our SEC filings can be found under the Investors and News section of our website.

Speaker Change: Earlier this afternoon, we should have pressed release, then include the summary of our second quarter, 2024, financial results and highly-tracing progress at the stomachs.

Speaker Change: We encourage everyone to read today's press release in the Associated Materials, which have been filed with the SEC.

Speaker Change: Additionally, the press release, recording of this call, and our SEC filings can be found under the investors and new section for a website.

Christopher Ogden: With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on the company's progress and pipeline. Keep for and cover the finances for the quarter, and we open up the call for Q&A.

Christopher Ogden: With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on the company's progress and pipeline before I cover the financials for the quarter, and we open up the call for Q&A. With that, I'll turn the call over to Sean.

Speaker Change: with me on the call today is Dr. Sean McCarthy, St. Thomas's Chief Executive Officer and Chairman.

Speaker Change: shall provide an update on the company's progress and pipeline to cover the finances for the quarter and we open up the call for Q&A. With that, I'll turn the call over to Sean.

Sean Mccarthy: With that, I will turn the call over to Sean.

Sean Mccarthy: Thanks, Chris, and good afternoon, everyone. We're delighted today to provide an update on our recent progress, which includes the continued development of CX904 in phase one dose escalation and clinical study initiation for our newest whole-year programs, CX2051 and CX801. The CytomX ProBody therapeutic platform encompasses more than a decade of innovation in antibody masking and conditional activation, and it's designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undruggable or significantly limited by the therapeutic window.

Sean Mccarthy: Thanks, Chris, and good afternoon, everyone. We're delighted today to provide an update on our recent progress, which includes the continued development of CX-904 and Phase 1-DOS escalation and clinical study initiation for our newest polio programs: CX-2051 and CX-801. PhytomX's pro-body therapeutic platform encompasses more than a decade of innovation in antibody masking and conditional activation. And it's designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undruggable or significantly limited by therapeutic window. CytomX currently has 15 active programs across our internal and partnered research and development activities, including three clinical stage pro-body therapeutics designed to address large patient populations.

Sean Mccarthy: So it's only providing therapeutic platform and encompasses more than a decade of innovation in antibody masking and conditional activation.

Sean Mccarthy: and is designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undrugable or significantly limited by therapeutic window.

Sean Mccarthy: CytomX currently has 15 active programs across its internal and partnered research and development activities, including three clinical-stage pro-body therapeutics designed to address large patient populations. Based on our continued strong execution, CytomX is currently very well positioned to build value and make a meaningful difference for cancer patients.

Sean Mccarthy: SITEMATICS currently has 15 active programs across our internal and partnered research and development activities, including three clinical stage pro-body therapeutics designed to address large patient populations.

Sean Mccarthy: Based on our continued strong execution, CytomX is currently very well positioned to build value and make a meaningful difference for cancer patients.

Speaker Change: Based on our continued strong execution, site service is currently very opposition to build value and make a meaningful difference for cancer patients.

Sean Mccarthy: Let me dive right in and start with CX-904, our marked pro-body T-cell engager targeting EGFR. Last quarter, we announced positive initial Phase 1-A clinical data for CX-904, which was an important first step in the clinical development of this program. EGFR is a very attractive target given its broad expression across multiple tumor types and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapy. CS904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T cell-mediated killing to tumor cells via CD3 binding. EGFR CD3 has previously been considered an attractive but undruggable target combination because of the widespread expression of EGFR in normal tissues.

Sean Mccarthy: Let me dive right in and start with CX904, a masked pro-body T-cell engager targeting EGFR. Last quarter, we announced positive initial Phase 1a clinical data for CX904, which was an important first step in the clinical development of this program. EGFR is a very attractive target, given its broad expression across multiple tumor types and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapies. CX904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T-cell mediated killing to tumor cells via CD3 binding.

Speaker Change: Let me dive right in and start with CX904, a masked pro-body T-cell engager targeting EGFR.

Speaker Change: Last quarter, we announced positive initial phase 1, a clinical data for CX904, which was an important first step in the clinical development of this program.

Speaker Change: EGFR is a very attractive target given its broad expression across multiple trimotides and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapies.

Speaker Change: CS904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T-cell mediated killing to tumor cells via CD3 binding.

Sean Mccarthy: EGFR-CD3 has previously been considered an attractive but undruggable target combination because of the widespread expression of EGFR in normal tissue. In the absence of masking, we would expect an EGFR-CD3 bispecific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome.

Speaker Change: EGFR-CD3 has previously been considered an attractive but undruggable target combination because of the widespread expression of EGFR in normal tissues.

Sean Mccarthy: In the absence of masking, we would expect an EGFR CD3 by specific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome. By using the CytomX Pro body platform to mark both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination, and we've been very encouraged by our clinical findings reported today. In May, we were delighted to release positive initial phase 1A dose of collision results for CX904, achieving our early phase 1 goals. In this first stage, we released for CX904 based on an April 16th, 2024, data cutoff, we reported on 35 heavily pretreated patients with a median of four prior lives of therapy.

Speaker Change: In the absence of masking, we would expect an EGFR-CD3 bispecific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome.

Sean Mccarthy: By using the CytomX ProBody platform to mask both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination, and we've been very encouraged by our clinical findings reported to date. In May, we were delighted to release positive initial Phase 1a dose escalation results for CX904, achieving our early Phase 1 goals. In this first data release for CX904 based on an April 16, 2024 data cutoff, we reported on 35 heavily pretreated patients with a median of four prior lines of therapy.

Speaker Change: By using the CytomX ProBody platform to mask both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination, and we've been very encouraged by our clinical findings reported to date.

Speaker Change: In May, we were delighted to release positive initial Phase 1a dose escalation results for CX904, achieving our early Phase 1 goals.

Speaker Change: In this first stage release for CX904 based on an April 16th, 2024 data cut off. We reported on 35 heavily pre-treated patients with a median of four prior lines of therapy.

Sean Mccarthy: The initial 60 profile of CX904 looks very encouraging; specifically, in step-dosing cohorts up to a target dose of 10 milligrams, we did not see any cytokine release syndrome, and across all 35 patients treated with non-step and step-dosing schedules, we saw only one grade 3 rash. In common with certain other T cell engages, we observed some muscular skeletal events that were manageable. In part, with totalus and ribopropyl axis, these early findings show that masking is effectively blunting CRS and other toxicities that would be expected for the corresponding unmasked EGFR CD3 T cellingator. In the context of this emerging favorable 70 profile, we also reported encouraging early signs of single-agent anti-catsuractivity for CX904.

Sean Mccarthy: The initial safety profile of CX904 looks very encouraging, specifically in step-dosing cohorts up to a target dose of 10 mg. We did not see any cytokine release syndrome, and across all 35 patients treated with non-step and step-dosing schedules, we saw only one grade 3 rash. In common with certain other T cell engagements, we observed some musculoskeletal events that were manageable, in part with total loss of my prophylaxis.

Speaker Change: The initial safety profile of CX904 looks very encouraging, specifically in step-dosing cohorts up to a target dose of 10 mg.

Speaker Change: We did not see any cytokine release syndrome, and across all 35 patients treated with non-STEP and STEP dosing schedules, we saw only one grade 3 rash.

Speaker Change: In common with certain other T-cell engages, we observe some muscular skeletal events that were a manageable, in part with totalism and prophylaxis.

Sean Mccarthy: These early findings show that masking is effectively blunting CRS and other toxicities that would be expected for the corresponding unmasked EGFR-CD3 T cell engagement. In the context of this emerging favorable safety profile, we also reported encouraging early signs of single-agent anti-capture activity for CX904. In 26 efficacy-evaluable patients treated at doses above 750 micrograms, we observed eight measurable tumor reductions, including confirmed partial responses in two of six efficacy-evaluable patients with pancreatic ductal adenocarcinoma.

Speaker Change: These early-fighting shows that masking is effectively blunting CRS and other atrocities that would be expected for the corresponding unmasked EGFRCD3 T-celligator.

Speaker Change: In the context of this emerging favorable safety profile, we also reported encouraging early signs of single-agent anti-cancer activity for CX904.

Sean Mccarthy: In 26 efficacy of valuable patients treated at doses above 750 micrograms, we observed eight measurable tumor reductions, including confirmed partial responses in two of six efficacy of valuable patients with pancreatic ductal adenocarcinoma. These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies. However, EGFR is expressed in more than 90 percent of pancreatic cancer patients, but our data suggests that CD3-mediated T cell killing via EGFR binding can be effective in this cancer type. Moreover, there's also increasing evidence from others in the field that pancreatic cancer can be immune competent and manate a T cell response.

Speaker Change: In 26 efficacy-evaluable patients treated at doses above 750 mcg, we observed 8 measurable tumor reductions, including confirmed partial responses in 2 of 6 efficacy-evaluable patients with pancreatic ductal adenocarcinoma.

Sean Mccarthy: These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies. However, EGFR is expressed in more than 90% of pancreatic cancer patients, and our data suggest that CD3-mediated T-cell killing via EGFR binding can be effective in this cancer type.

Speaker Change: These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies.

Speaker Change: However, EGFR is expressed in more than 90% of pancreatic cancer patients, and our data suggests that CD3-mediated T-cell killing via EGFR binding can be effective in this cancer type.

Sean Mccarthy: Moreover, there's also increasing evidence from others in the field that pancreatic cancer can be immune-competent and mount a T cell response. This is based on progress with neoadjuvant vaccines and recent data from ASCO 2024 for a Claudin 18 CD3 T cell engager. In our view, our early CX904 results in pancreatic cancer highlight exactly why CX904 was designed, and they illustrate the power of antibody masking, opening a therapeutic window for an undruggable T cell engager target and bringing a unique pharmacology to a cancer type of high incidence and significant unmet medical need.

Speaker Change: Moreover, there is also increasing evidence from others in the field that pancreatic cancer can be immune competence and grants a T-shirt response.

Sean Mccarthy: This is both based on progress with neoadshed vaccines and recent data from ASCO 2024 for a clotted 18 CD3 T cell engaging. In our view, our early CX904 results in pancreatic cancer highlight exactly why CX904 was, and they illustrate the power of antibody market, opening a therapeutic window for an undrugable P cell-engager target and bringing a unique pharmacology to a cancer type of high incidence and significant unmet medical need. Indeed, pancreatic ductal adenocarcinoma is currently the third leading cause of cancer death in the US, and second-line treatments have response rates of less than 10%, and only two to three months of progression-free survival, leaving a major need for new therapies.

Speaker Change: This is both based on progress with neoadjuvant vaccines and recent data from ASCO 2024 for a Claudin 18 CD3 T cell engager.

Speaker Change: In our view, our early CX904 results in pancreatic cancer highlight exactly why CX904 was designed.

Speaker Change: and they illustrate the power of antibody masking, opening a therapeutic window for an undruckable peace-selling gauge target, and bringing a unique pharmacology to a cancer type of high incidents and significant unmet medical need.

Sean Mccarthy: Indeed, pancreatic ductal adenocarcinoma is currently the third leading cause of cancer death in the U.S., and second-line treatments have response rates of less than 10 percent and only two to three months of progression-free survival, leaving a major need for new therapy. We are now accelerating enrollment in pancreatic cancer to further explore this signal. And in parallel, we're prioritizing enrollment in head and neck and non-small cell lung cancers where we have not previously enrolled a meaningful number of patients in the initial dose escalation phase.

Speaker Change: is currently the third leading cause of cancer death in the U.S., and second-line treatments have response rates of less than 10 percent. I know only two to three months of progression freeze survival, leaving a major need for new therapies.

Sean Mccarthy: We are now accelerating enrollment in pancreatic cancer to further explore this signal, and in parallel, we're prioritizing enrollment in head and neck and non-small cell lung cancers where we had not previously enrolled a meaningful number of patients in the initial dose escalation. We continue to enroll on multiple dose levels to further inform the selection of a recommended Phase 1B dose or potentially doses.

Speaker Change: We are now accelerating enrollment in pancreatic cancer to further explore this signal, and in parallel, we're prioritizing enrollment in head and neck and non-small cell lung cancers where we had not previously enrolled a meaningful number of patients in the initial dose escalation.

Sean Mccarthy: We continue to enroll at multiple dose levels to further inform the selection of a recommended phase 1b dose or, potentially, doses. Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX904 phase 1b expansions in select EGFR-expressing tumor types. And we expect to provide a CX904 program update by the end of 2024. Now, turning now to CX2051, our wholly owned, first-in-class, EPCAM-directed ProBody ADC.

Speaker Change: We continue to enroll at multiple dose levels to further inform the selection of a recommended phase 1b dose or potentially doses.

Sean Mccarthy: Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX904 Phase 1B expansions in select EGFR-expressing tumour sites, and we expect to provide a CX904 program update by the end of 2024.

Speaker Change: Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX904 Phase 1b expansions in select EGFR-expressing tumor types.

Speaker Change: and we expect to provide a CX 904 program update by the end of 2024.

Sean Mccarthy: Turning now to CX2051, our wholly owned first-in-class ECAM-directed ProBODY ADC. ECAM or Epithelial Cell Adhesion Molecule is a high potential oncology target with high cell surface expression in many solid tumour types and that has been implicated in many aspects of cancer biology. Anti-ATCAM therapeutic strategies have previously been translated into clinical activity, but to date, clinical success has been limited to local administration because ECAM is present in most normal epithelial tissues. Efforts to generate systemically admitted anti-ATCAM therapies have not been successful to date due to toxicities in epithelial tissues, including in the gastrointestinal tract.

Speaker Change: Just a little bit.

Speaker Change: Turning now to CX2051 are wholly owned first in class at Cam Directed Probody ADC.

Sean Mccarthy: EPCAM, or epithelial cell adhesion molecule, is a high potential oncology target with high cell surface expression in many solid tumor types and has been implicated in many aspects of cancer biology. Anti-EPCAM therapeutic strategies have previously been translated into clinical activity, but to date, clinical success has been limited to local administration because EPCAM is present in most normal epithelial tissues. Efforts to generate systemically administered anti-EPCAM therapies have not been successful to date due to toxicities in epithelial tissues, including in the gastrointestinal tract.

Speaker Change: Epcam, or epithelial cell adhesion molecule, is a high potential oncology target with high cell surface expression in many solid tumor types and that has been implicated in many aspects of cancer biology.

Speaker Change: and the F-CAM therapeutic strategies have previously been translated into clinical activity but to date clinical success has been limited to local administration because that camera is present in most normal epidemiological tissues.

Speaker Change: Thank you.

Speaker Change: Efforts to generate systemically administered anti-EPCAM therapies have not been successful to date due to toxicities in epithelial tissues, including in the gastrointestinal tract.

Sean Mccarthy: Our innovative drug candidate, CX2051, is a marked ADC tailored to optimize the therapeutic window for Epcare and expressing epithelial cancers by marking the antibody to reduce binding and normal tissues, but allowing activation in tumour tissue. We have armed the antibody with a psychostoxic payload based on cancer teacin, a topyl summarize one inhibitor, which is a class of drug that has shown potent clinical anti-catch activity in the ADC context for multiple targets, leading in recent years to dramatic advances for patients. CX2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer. And like EGFR, I discussed previously in the context of CX904, CX2051 could also potentially address large patient populations because Epcare is highly expressed across many indications including colorectal, lung, gastric, endometrial, pancreatic, and ovarian cancer.

Sean Mccarthy: Our innovative drug candidate, CX2051, is a masked ADC tailored to optimize the therapeutic window for Epcan-expressing epithelial cancers by masking the antibody to reduce binding in normal tissues but allowing activation in tumor tissue. We have armed the antibody with a cytotoxic payload based on cantothecin, a topoisomerase I inhibitor, which is a class of drug that has shown potent clinical anticancer activity in the ADC context for multiple targets, leading in recent years to dramatic advances for patients.

Speaker Change: Our Innovative Drug Candidate, CS2051, is a masked ADC.

Speaker Change: tailored to optimize the therapeutic window for Epcan-expressing epithelial cancers by masking the antibody to reduce binding in normal tissues, but allowing activation in tumor tissue.

Speaker Change: We have armed the antibody with a side-stop stick payload based on cancer season.

Speaker Change: Atopisomerase-1 inhibitor.

Speaker Change: which is a class of drug that has shown potent clinical anti-cancer activity in the ADC context.

Speaker Change: for multiple targets, leading in recent years to chromatic advances for patients.

Sean Mccarthy: CX2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer. And like EGFR discussed previously in the context of CX904, CX2051 could also potentially address large patient populations because Epcan is highly expressed across many indications, including colorectal, lung, gastric, endometrial, pancreatic, and ovarian cancer. In April of this year, we treated our first patient in our phase one dose escalation study of CX2051, and we're now already enrolling patients into our third patient cohort.

Speaker Change: CX2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer.

Speaker Change: and like EGFR discussed previously in the context of CX904, CX251.

Speaker Change: could also potentially address large patient populations because EPCAM is highly expressed across many indications, including colorectal, lung, gastric, endometrial, pancreatic, and ovarian cancers.

Sean Mccarthy: In April of this year, we treated our first patients in our phase one dose at Galatian study of CX-2051, and we're now already enrolling into our third patient cohort. At this stage, enrollment is principally focused in Colorado Cancer, where Etkham expression is particularly high, and we're really looking forward to seeing what CX-2051 could do for patients. And based on this progress, we remain on track to share initial data for CX-2051 in the first half of 2025.

Speaker Change: In April of this year, we treats it our first patients in our phase 1 dose escalation study of CX-5051. And we're now ready and rolling into our third patient cohort.

Sean Mccarthy: At this stage, enrollment is principally focused on colorectal cancer, where EPCAM expression is particularly high, and we're really looking forward to seeing what CX2051 could do for patients. And based on this progress, we remain on track to share initial data for CX2051 in the first half of 2025.

Speaker Change: At this stage, enrollment is principally focused in colorectal cancer, where EPCAM expression is particularly high, and we're really looking forward to seeing what CX2051 can do for patients.

Speaker Change: And based on this progress, we remain on track to share initial data for CX2051 in the first half of 2025.

Sean Mccarthy: Now, turning to our third clinical program, CX-801, which is our Julie Mask Interfered Alpha 2B Pro body cytokines. We're excited about CX-801 as a foundational immunomacology agent with potential for activity across multiple tumor types, including those that are insensitive to current immunomacology therapies. Interferred is a compelling and differentiated opportunity for a mass cytokine for two key reasons. First, the biology of Inspiron is unique in that it has been shown to directly kill tumor cells, and Inspiron also increases adjutant presentation to activate T cells, making it an ideal mechanism for combination with checkpoints inhibition. Secondly, as a previously approved cancer therapy, Inspiron has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD-1.

Sean Mccarthy: Now turning to our third clinical program, CX801, which is our dually masked interferon alpha 2b probody cytokine. We're excited about CX801 as a foundational immuno-oncology agent with potential for activity across multiple tumor types, including those that are insensitive to current immuno-oncology therapy. Interferon is a compelling and differentiated opportunity for a mass cytokine for two key reasons. First, the biology of interferon is unique in that it has been shown to directly kill tumor cells.

Speaker Change: Now turning to our third clinical program, CX801, which is our dually masked interferon alpha 2B probody cytokine.

Speaker Change: We're excited about CX801 as a foundational immuno-oncology agent with potential for activity across multiple tumor types, including those that are insensitive to current immuno-oncology therapies.

Speaker Change: Interferon is a compelling and differentiated opportunity for a mass cytokine for two key reasons.

Speaker Change: First, the biology of interferon is unique in that it has been shown to directly kill tumor cells.

Sean Mccarthy: Secondly, as a previously approved cancer therapy, interferon has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD-1. The use of interferon at its broader development as a systemic therapy has been limited, however, due to systemic toxicities. Our preclinical data for CX801, most recently presented at CITSE 2023, demonstrate synergy for our masked interferon alpha with PD-1 inhibition, both in terms of antitumor activity and activation of the tumor inflammatory microenvironment. Moreover, we've also shown that systemic activity of our mass interferon is significantly reduced, and overall tolerability is markedly improved compared to the unmasked cytokine in animal models.

Speaker Change: and it's a firm on also increases Aged in Presentations to activate T-cells, making it an ideal mechanism for combination with checkpoints inhibition.

Unknown Executive: 24 Financial Results Call. Please be aware that today's call is being recorded.

Unknown Executive: I want to kind of call the call over to your host for today Chris Ogden, CytomX's Chief Financial Officer. Please go ahead. Thank you.

Speaker Change: Secondly, as a previously approved cancer therapy, Interferon has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD-1.

Christopher Ogden: 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 looking statements because four looking statements relate to the future. They are subject to inherent uncertainty. These and risks, they're difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public violence with the SEC at SEC.gov.

Sean Mccarthy: The use of Inspiron and its broader development as a systemic therapy has been limited, however, due to systemic toxicities. Our preclinical data for CX-801, most recently presented at 60-2023, demonstrates synergy for our massed Inspiron Alpha with PD1 inhibition, both in terms of anti-tumor activity and activation of the systemic activity of our massed Inspiron, is significantly reduced, and overall tolerability is markedly improved compared to the unmassed cytokine in animal models. Our phase one dose escalation study is now open, and our first clinical site has been activated. This study will evaluate safety and signs of clinical activity for CX-801 as a monotherapy and in combination with Ketruder under a collaboration and supply agreement that we recently executed with Merck.

Speaker Change: The use of interferon at its broader development as a systemic therapy has been limited however due to systemic toxicities.

Speaker Change: Our preclinical data for CX801, most recently presented at CITSE 2023, demonstrates synergy for our masked interferon alpha with PD-1 inhibition, both in terms of anti-tumor activity and activation of the tumor inflammatory microenvironment.

Christopher Ogden: We undertake no obligations to update any four looking statements, whether as a result of new information, future developments or otherwise. Earlier this afternoon, we issued a press release that includes the summary of our second quarter, 2024 financial results and highly treason progress at PhytomX. We encourage everyone to read today's press release in the associated materials, which have been filed with the SEC. Additionally, the press release, recording of this call and our SEC filings can be found under the investors and news section of our website.

Speaker Change: Moreover, we've also shown that systemic activity of our mass interferon is significantly reduced and overall tolerability is markedly improved compared to the unmasked cytokine in animal models.

Sean Mccarthy: Our phase one dose escalation study is now open, and our first clinical site has been activated. This study will evaluate safety and signs of clinical activity for CX801 as monotherapy and in combination with Keytruda under a collaboration and supply agreement that we recently executed with Merck. We anticipate initial data for CX801 in the second half of 2025.

Speaker Change: Our phase one dose escalation study is now open and our first clinical site site has been activated.

Speaker Change: This study will evaluate safety and signs of clinical activity for CX801 as a monotherapy and in combination with Keytruda under a collaboration and supply agreement that we recently executed with Merck.

Sean Mccarthy: We anticipate initial data for CX-801 in the second half of 2025.

Speaker Change: We anticipate initial data for CX801 in the second half of 2025.

Sean Mccarthy: On the collaboration front, we continue to have more than 10 ongoing research programs with our partners, which include Angen, Estellus, BMS, Moderna, and Regeneron, with the majority of our partners. Today, in 2024, we have already achieved $10 million in pre-clinical milestones through our collaboration with Estellus, and across our collaborations, we have the potential to earn additional milestones over the next 12 to 18 months and beyond. Scythemic also retains significant US commercial rights and certain partnerships, including with Estellus for a select number of programs, and with Angen as part of our global developmentalised on CX-904.

Sean Mccarthy: On the collaboration front, we continue to have more than 10 ongoing research programs with our partners, which include Angen, Astellas, BMS, Moderna, and Regeneron, with the majority of our pilot research currently focused on masked T cell engagers. To date, in 2024, we've already achieved $10 million in preclinical milestones through our collaboration with Astellas. And across our collaborations, we have the potential to earn additional milestones over the next 12 to 18 months and beyond. CytomX also retains significant U.S. commercial rights in certain partnerships, including with Astellas for a select number of programs and with Amgen as part of our global development alliance on CX904.

Speaker Change: On the collaboration front, we continue to have more than 10 ongoing research programs with our partners, which include Angen, Astellas, BMS, Moderna, and Regeneron, with the majority of our partnered research currently focused in masked T cell engagers.

Sean Mccarthy: With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on the company's progress and pipeline.

Christopher Ogden: Keep for and cover the finances for the quarter and we open up the call for Q&A.

Speaker Change: Today, in 2024, we've already achieved $10,000 in pre-clinical milestones through our collaboration with Estelle and across our collaborations, we have the potential to earn additional milestones over the next 12 to 18 months and beyond.

Sean Mccarthy: With that, I will turn the call over to Sean. Thanks, Chris and good afternoon, everyone. We're delighted today to provide an update on our recent progress, which includes the continued development of CX-904 and Phase 1-DOS escalation and clinical study initiation for our newest polio programs. CX-2051 and CX-801.

Speaker Change: Thanks for watching, and don't forget to like, share, and subscribe to our channel.

Speaker Change: So, it's also obtained significant US commercial rights and certain partnerships, including with a Stellus for a select number of programs and with Amgen as part of our global development alliance on CX904, and partnering continues to be a cornerstone of our business strategy.

Sean Mccarthy: And partnering continues to be a cornerstone of our business strategy.

Sean Mccarthy: And partnering continues to be a cornerstone of our business strategy. Before handing over to Chris to cover the financials, let me first congratulate him on his promotion to Chief Financial Officer. We're really excited to have Chris's cross-functional leadership and strategic finance experience in this key role. My colleagues and I look forward to continuing to partner with Chris as we build value in CytomX over the near and long term. With that, let me hand over to Chris to provide an update on our finances.

Sean Mccarthy: PhytomX's pro-body therapeutic platform encompasses more than a decade of innovation in antibody masking and conditional activation. And it's designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undruggable or significantly limited by therapeutic window. CytomX currently has 15 active programs across our internal and partnered research and development activities, including three clinical stage pro-body therapeutics designed to address large patient populations. Based on our continued strong execution, CytomX is currently very well positioned to build value and make a meaningful difference for cancer patients.

Sean Mccarthy: Before handing over to Chris to cover financials, let me first congratulate him on his promotion to Chief Financial Officer. We're really excited to have Chris's cross-functional leadership and strategic financial experience in this key role. My colleagues and I look forward to continuing to partner with Chris as we build value in CytomX over the near and long term.

Speaker Change: Before handing over to Chris to cover financials, let me first congratulate him on his promotion to Chief Financial Officer. We're really excited to have Chris's cross-functional leadership and strategic finance experience in this key role. My colleagues and I look forward to continuing to partner with Chris as we build value in CytomX over the near and long term.

Christopher Ogden: With that, let me hand over to Chris to provide an update on our finances. Thank you, Sean. It is a privilege to be part of the CytomX team, and I look forward to helping lead the company towards multiple new treatment options for patients over the long term.

Christopher Ogden: Thank you, Sean. It is a privilege to be part of the CytomX team, and I look forward to helping lead the company towards multiple new treatment options for patients over the long term. Now turning to the second quarter results. I am pleased to be able to share an update on our financials with everyone today. CytomX finished the second quarter of 2024 with $137 million in cash, cash equivalents, and investments, versus $150 million in cash at the end of the first quarter of 2024.

Speaker Change: With that, let me hand over to Chris to provide an update on our finances.

Chris Ogden: Thank you, Sean. It is a privilege to be part of the sitomics team, and I look forward to helping lead the company towards multiple new treatment options for patients over the long-term.

Christopher Ogden: Now, turning to the second quarter results, I am pleased to be able to share an update on our financials with everyone today. CytomX finished the second quarter of 2024 with 137 million in cash, cash equivalence, and investments versus 150 million in cash at the end of the first quarter of 2024. We expect our cash balance will fund the operations of the company to the end of 2025. Also, as a reminder, this cash guidance does not assume any additional milestones from existing collaborations or any new business development.

Sean Mccarthy: Let me dive right in and start with CX-904, our marked pro-body T-cell-engager targeting EGFR. Last quarter, we announced positive initial Phase 1-A clinical data for CX-904, which was an important first step in the clinical development of this program. EGFR is a very attractive target given its broad expression across multiple tumor types and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapy. CS904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T cell mediated killing to tumor cells via CD3 binding.

Chris Ogden: Now, turning to the second quarter results, I am pleased to be able to share an update on our financials with everyone today.

Speaker Change: Sectomics finished the second quarter of 2024 with $137 million in cash, cash equivalents and investments versus $150 million in cash at the end of the first quarter of 2024.

Christopher Ogden: We expect our cash balance will fund the operations of the company to the end of 2025. Also, as a reminder, this cash guidance does not assume any additional milestones from existing collaborations or any new business development.

Chris Ogden: We expect our cash balance will fund the operations of the company to the end of 2025.

Speaker Change: Also, as a reminder, this cast guidance does not assume any additional milestones from existing collaborations or any new business development.

Christopher Ogden: Operationally, we continue to be focused on controlling cost and disciplined capital allocation, investing behind the clinical progression of our LEAD pipeline program. Now, moving on to revenue and operating expenses for the quarter. For the second quarter of 2024, revenue was $25.1 million, compared to $24.7 million in the second quarter of 2023. Operating expenses for the second quarter were $33.6 million. R&D expenses were $25.2 million in the second quarter of 2024, an increase of $4.5 million versus Q2 2023, driven by investments in our clinical pipeline.

Christopher Ogden: Operationally, we continue to be focused on controlling costs and disciplined capital allocation, investing behind the clinical progression of our lead pipeline programs. Now, moving on to revenue and operating expenses for the quarter. For the second quarter of 2024, revenue was 25.1 million compared to 24.7 million in the second quarter of 2023. Operating expenses for the second quarter were 33.6 million. R&D expenses were 25.2 million in the second quarter of 2024 and increased a 4.5 million versus Q2 2023, driven by investments in our clinical pipeline. G&A expenses increased by 1 million during the three months ended June 30, 2024, to 8.4 million compared to 7.4 million for the course finding period in 2023.

Speaker Change: Operationally, we continue to be focused on controlling cost and disciplined capital allocation, investing behind the clinical progression of our lead pipeline programs.

Sean Mccarthy: EGFR CD3 has previously been considered an attractive but undruggable target combination because of the widespread expression of EGFR in normal tissues. In the absence of masking, we would expect an EGFR CD3 by specific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome. By using the CytomX Pro body platform to mark both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination and we've been very encouraged by our clinical findings reported today.

Christopher Ogden: G&A expenses increased by $1 million during the three months ended June 30, 2024, to $8.4 million, compared to $7.4 million for the corresponding period in 2023. Overall, our prudent financial management of the company and focused capital allocation has resulted in continued balance sheet strength and positions us to deliver meaningful value through our pipeline over the next 12 to 18 months and in the long term. Now, I'll turn the call back to Sean for his closing remarks.

Speaker Change: Now, moving on to revenue and operating expenses for the quarter. For the second quarter of 2024, revenue was $25.1 million, compared to $24.7 million in the second quarter of 2023.

Speaker Change: Operating expenses for the second quarter were $33.6 million.

Speaker Change: R&D expenses were $25.2 million in the second quarter of 2024, an increase of $4.5 million versus Q2 2023, driven by investments in our clinical pipeline.

Speaker Change: G&A expenses increased by 1 million during the three months and did June 30, 2024, 28.4 million, compared to 7.4 million for the corresponding period in 2023.

Sean Mccarthy: In May, we were delighted to release positive initial phase 1A dose of collision results for CX904 achieving our early phase 1 goals. In this first stage, we released for CX904 based on an April 16th, 2024 data cutoff, we reported on 35 heavily pretreated patients with a median of four prior lives of therapy. The initial 60 profile of CX904 looks very encouraging, specifically in step-dosing cohorts up to a target dose of 10 milligrams, we did not see any cytokine release syndrome and across all 35 patients treated with non-step and step-dosing schedules, we saw only one grade 3 rash.

Christopher Ogden: Overall, our prudent financial management of the company and focused capital allocation has resulted in continued balance sheet strength and positions up to deliver meaningful value through our pipeline over the next 12 to 18 months and in the long term.

Speaker Change: Overall, our prudent financial management of the company and focused capital allocation has resulted in continued balance sheet strength and positions us to deliver meaningful value through our pipeline over the next 12 to 18 months and in the long term.

Sean Mccarthy: Now, I'll turn the call back to Sean for closing remarks.

Sean Mccarthy: Thanks, Chris, and thanks, everyone, for joining us today. CytomX has continued to make excellent progress throughout 2024, and we believe the company outlook is very compelling as we drive forward with our multi-modality pro-body therapeutic pipeline. Our current pipeline reflects broad investments over time and deep learning as a leading innovator in the field of antibody masking and conditional activation. Our progress with CX904 positions CytomX at the forefront of the exciting field of T-cell engagers for solid tumors, and we, like many others, see this area as being on the cusp of breakthroughs for patients.

Sean Mccarthy: Thank you, Chris, and thanks everyone for joining us today. So Thomas has continued to make excellent progress throughout 2024, and we believe the company outlook is very compelling as we drive forward with our multi-vodality pro body therapeutic pipeline. Our current pipeline reflects broad investments over time and deep learning as a leading innovator in the field of antibody masking and conditional activation. Our progress was CS904, a position of siteomics at the forefront of the exciting field of T-cell engages for solid tumors, and we, like many others, see this area as being on the cusp of breakthroughs for patients.

Speaker Change: Now, I'll turn the call back to Sean for closing remarks.

Sean: Thanks Chris and thanks everyone for joining us today.

Sean: CytomX has continued to make excellent progress throughout 2024, and we believe the company outlook is very compelling as we drive forward with our multi-modality, pro-body therapeutic pipeline.

Sean Mccarthy: In common with certain other T cell engages, we observed some muscular skeletal events that were manageable. In part, with totalus and ribopropyl axis, these early findings show that masking is effectively blunting CRS and other toxicities that would be expected for the corresponding unmasked EGFR CD3 T cellingator. In the context of this emerging favorable 70 profile, we also reported encouraging early signs of single agent anti-catsuractivity for CX904. In 26 efficacy of valuable patients treated at doses above 750 micrograms, we observed eight measurable tumor reductions, including confirmed partial responses in two of six efficacy of valuable patients with pancreatic ductal adenocostinoma.

Speaker Change: Our current pipeline reflects broad investments over time and deep learning as a leading innovator in the field of antibody masking and conditional activation.

Sean: Our progress with CX904 positions CytomX at the forefront of the exciting field of T-cell engagers for solid tumors, and we, like many others, see this area as being on the cusp of breakthroughs for patients.

Sean Mccarthy: Siteomics continues to prosecute a multi-modality strategy, with each of CS904, CS2051, and CS801 being well-positioned for new clinical datasets over the next 18 months. Moreover, masking strategies, as exemplified by the Pro Body Therapeutic Platform, were growing strategic interest in the biopharma R&D area, and CytomX remains a recognized leader, having created this field.

Sean Mccarthy: CytomX continues to pursue a multimodality strategy with each of CX904, CX2051, and CX801 being well-positioned for new clinical datasets over the next 18 months. Moreover, masking strategies, as exemplified by the ProBody Therapeutic Platform, are of growing strategic interest in the biopharma R&D area, and CytomX remains a recognized leader having created this field. In conclusion, here at CytomX, we remain highly committed and focused on creating innovative treatments for people living with cancer, and we believe our ProBody pipeline has the potential to deliver safer, more effective therapy.

Sean: Shhh!

Sean: CytomX continues to prosecute a multimodality strategy with each of CX904, CX2051, and CX801 being well-positioned for new clinical datasets over the next 18 months.

Sean: Moreover, masking strategies, as exemplified by the ProBody Therapeutic Platform, are a growing strategic interest in the biopharma R&D area, and Cytomics remains a recognized leader having created this field.

Sean Mccarthy: In conclusion, here at CytomX we remain highly committed and focused on creating innovative treatments for people living with cancer, and we believe our Pro Body Pipeline has the potential to deliver safer, more effective therapies.

Sean Mccarthy: These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies. However, EGFR is expressed in more than 90 percent of pancreatic cancer patients, but our data suggests that CD3 mediated T cell killing via EGFR binding can be effective in this cancer type. Moreover, there's also increasing evidence from others in the field that pancreatic cancer can be immune competent and manate a T cell response.

Speaker Change: Inclusion here, aside term, we remain highly committed but focused on creating innovative treatments for people living with cancer and we believe our program body pipeline has the potential to deliver safer, more effective therapies.

Sean Mccarthy: I want to sincerely thank the patients who join our studies, their families, and our team for helping to drive our mission forward.

Sean Mccarthy: I want to sincerely thank the patients who join our studies, their families, and our team for helping to drive our mission forward. And with that, Operator, let's go ahead and open up the call for Q&A. Thank you.

Speaker Change: I want to sincerely thank the patients who join our studies, their families are not seen for helping to drive our mission forward and with that operator let's go ahead and open up the call for Q&A.

Unknown Executive: And with that operator, let's go ahead and open up the call for Q&A. Thank you. As a question, you will need to press Star 1-1 or telephone, and wait for you to be announced. To withdraw your question, please press Star 1-1 again. Please send our first question. We'll come to line up. Etzer Darout from BML Capital Markets.

Operator: Thank you. To ask a question, you will need to 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. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question will come from Etzer Darout from BMO Capital Markets. Your line is open.

Speaker Change: Thank you. To ask a question, you will need to 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. Please stand by while we compile the Q&A roster. One moment for our first question.

Sean Mccarthy: This is both based on progress with neoadshed vaccines and recent data from ASCO 2024 for a clotted 18 CD3 T cell engaging. In our view, our early CX904 results in pancreatic cancer highlight exactly why CX904 was and they illustrate the power of antibody market, opening a therapeutic window for an undrugable P cell-engager target and bringing a unique pharmacology to a cancer type of high incidence and significant unmet medical need. Indeed, pancreatic ductal adenocarcinoma is currently the third leading cause of cancer death in the US and second-line treatments have response rates of less than 10%, and only two to three months of progression-free survival, leaving a major need for new therapies.

Etzer Darout: Your line is open.

Speaker Change: Our first question will come from the line of Edzer Darao from BMO Capital Markets. Your line is open.

Etzer Darout: Great.

Etzer Darout: Great, thanks for taking the question. Just a quick one on CX904, if you know if you've had any more insights into sort of the correlation between efficacy and EGFR expression and what, you know, could be driving the activity that you're seeing in pancreatic cancer, and maybe just remind us about CX904. Can you discuss sort of the venue, if you kind of give them some thoughts on the venue where you'll be presenting this update by year-end? Thanks.

Sean Mccarthy: Thanks for taking a question. Just a quick one on CX904. If you know you had any more insights into sort of the correlation between efficacy and EGFR expression, and what you know could be driving the activity that you're seeing in pancreatic cancer, and maybe just remind us for CX904.

Edzer Darao: Great thanks for taking a question just a quick one on CX904 if you know you had any more insight into sort of the correlation between

Speaker Change: and Asia for Expression, and what could be driving the activity that you're seeing in Pancreatic Cancer and maybe just...

Sean Mccarthy: Can you discuss sort of the venue if you kind of give in some thoughts into sort of the venue where you'll be presenting this update on by your end? Thanks.

Speaker Change: Remind us for CX904, can you discuss sort of the venue, if you've kind of given some thoughts into sort of the venue where you'll be presenting this update by year-end? Thanks.

Sean Mccarthy: We are now accelerating enrollment in pancreatic cancer to further explore this signal and in parallel, we're prioritizing enrollment in head and neck and non-small cell lung cancers where we had not previously enrolled a meaningful number of patients in the initial dose escalation. We continue to enroll on multiple dose levels to further inform the selection of a recommended phase 1B dose or potentially doses.

Sean Mccarthy: Yeah, hi. Thanks for the questions. So we're considering to look at EGFR and how it relates to activity for CX904. As we mentioned, pancreatic cancer, like many others, expresses EGFR. More than 90% of pancreatic ductal adenocarcinoma expresses EGFR. So that's clearly relates to the activity that we're seeing. We were thinking in that too, as to specific correlations between target level and response.

Sean Mccarthy: Yeah, hi Etzer, thanks for the questions. So we're considering looking at EGFR and how it relates to activity for 904. As we've mentioned, pancreatic cancer, like many others, expresses EGFR; more than 90% of pancreatic ductal adenocarcinoma expresses EGFR. So, you know, that clearly relates to the activity that we're seeing, we thought, in that tumor. As to specific correlations between target level and response, I think that remains to be determined.

Speaker Change: Yeah, hi Etzer, thanks for the questions.

Speaker Change: So we're considering to look at EGFR and how it relates to activity for 904, as we've mentioned.

Speaker Change: you know, pancreatic cancer, like many others, expresses EGFR more than 90% of pancreatic ductal adenocross than I am at EGFR, so you know that that's uh...

Sean Mccarthy: Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX904 phase 1B expansions in select EGFR-expressing tumour sites, and we expect to provide a CX904 program update by the end of 2024.

Speaker Change: you know.

Speaker Change: that clearly relates to the activity that we're seeing, we were thinking in that tumor type, as to specific correlations between

Sean Mccarthy: I think that remains to be determined, and I would also say that, of course, for T cell engages, if we look at historical data from other programs, from other organizations, you know, these agents are quite different to functional blocking antibodies in that we wouldn't necessarily expect to require too much adegin to drive responses, but I think this is something we're still learning, both for 904 and in the field of T cell engages more broadly.

Sean Mccarthy: And I would also say that, of course, for T cell engagers, if we look at historical data from other programs, from other organizations, these agents are quite different to, you know, functional blocking antibodies in that we wouldn't necessarily expect to require too much antigen to drive responses. But I think this is something we're still learning, both for 904 and in the field of T cell engagers more broadly. In terms of the next update, as we mentioned, we're planning on an update by the end of the year.

Speaker Change: target level and response.

Speaker Change: I think that remains to be.

Speaker Change: Determined. And I would also say that, of course, for T-cell engagers...

Sean Mccarthy: Turning now to CX2051, our wholly owned first-in-class ECAM-directed ProBODY ADC. ECAM or Epithelial Cell Adhesion Molecule is a high potential oncology target with high cell surface expression in many solid tumour types and that has been implicated in many aspects of cancer biology. Anti-ATCAM therapeutic strategies have previously been translated into clinical activity, but to date clinical success has been limited to local administration because ECAM is present in most normal epithelial tissues.

Speaker Change: If we look at historical data from other programs, from other organizations

Speaker Change: You know, these agents are quite different to, you know, functional blocking antibodies in that.

Speaker Change: We wouldn't necessarily expect to require...

Speaker Change: Too much, and, again, to drive responses, but I think this is something we're still learning both for 904 and in the field of T-cell engages more broadly.

Sean Mccarthy: In terms of the next update, so as we mentioned, we're planning on an update by the end of the year that could take the form of a strategic update in terms of next steps for the program with actual data that underpins that strategic update, which will of course include dialogue with Amgen, with that data coming at a future date at a venue to be determined. So no additional colour on that at this time.

Speaker Change: Um...

Speaker Change: In terms of the next update, so yeah, as we mentioned, we're planning on an update by the end of the year.

Sean Mccarthy: That could take the form of a strategic update in terms of next steps for the program with actual data that underpins that strategic update, which will, of course, include a dialogue with Amgen with that data coming at a future date at a venue to be determined. So no additional color on that at this time. Great, thank you.

Speaker Change: That could take the form of a strategic update in terms of next steps for the program with actual

Sean Mccarthy: Efforts to generate systemically admitted anti-ATCAM therapies have not been successful to date due to toxicities in epithelial tissues, including in the gastrointestinal tract. Our innovative drug candidate, CX2051, is a marked ADC tailored to optimize the therapeutic window for Epcare and expressing epithelial cancers by marking the antibody to reduce binding and normal tissues, but allowing activation in tumour tissue. We have armed the antibody with a psychostoxic payload based on cancer teacin, a topyl summarize one inhibitor, which is a class of drug that has shown potent clinical anti-catch activity in the ADC context for multiple targets leading in recent years to dramatic advances for patients.

Speaker Change: Data that underpins that strategic update, which will of course include dialogue with Amgen, with that data coming out of future date, had a venue to be determined, so no additional color on that at this time.

Etzer Darout: Great. Thank you.

Malcolm Kuno: Thank you. One moment for our next question, and our next question comes from Malcolm Kuno from JPM. Your line is open.

Unknown Executive: One moment for our next question.

Speaker Change: Great, thank you.

Speaker Change: Thank you. One moment for our next question.

Malcolm Kuno: And our next question, conflina Malcolm Kuno from KPM. Your line is open.

Malcolm Kuno: Hi, thank you for taking the question. This is Malcolm on behalf of Anupam Rama.

Speaker Change: And our next question comes from Malcolm Kuno from JPM. Your line is open.

Malcolm Kuno: Hi, thank you for taking the question.

Malcolm Kuno: This is Malcolm from Anupam Rama. So you talked about this of the 904 update at the end of year. How should you think about the size of maybe the data that we may receive, and then given that you saw in a signal earlier this year, how are you thinking about prioritizing indications? Yeah, thanks, Malcolm. So again, with regard to, you know, our goal for an update by the end of this year, you know, our overriding focus in the second half of 2024 is to generate additional data to facilitate strategic dialogue with our partner and then regarding potential next steps with the program. The obvious next step, if the data supports it, of course, is to move from phase one A to phase one B.

Malcolm Kuno: Hi, thank you for taking the question. This is Malcolm on for Honored Palm Rama.

Malcolm Kuno: So you've talked about the scope of the 904 update at the end of the year. How should we think about the size of maybe the data that we may receive? And then, given that you saw a signal earlier this year, how are you thinking about prioritizing indications? Yeah.

Malcolm Kuno: So, you've talked about this month of the 904 update at the end of the year. How should we think about the size of maybe the data that we may receive? And then given that you saw in a signal earlier this year, how are you thinking about prioritizing indications?

Sean Mccarthy: CX2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer. And like EGFR, I discussed previously in the context of CX904, CX2051 could also potentially address large patient populations because Epcare is highly expressed across many indications including colorectal lung gastric, endometrial pancreatic, and ovarian cancer. In April of this year, we treated our first patients in our phase one dose at Galatian study of CX-2051, and we're now already enrolling into our third patient cohort. At this stage, enrollment is principally focused in Colorado Cancer, where Etkham expression is particularly high, and we're really looking forward to seeing what CX-2051 could do for patients.

Sean Mccarthy: Yeah, thanks, Malcolm. So again, with regard to our goal for an update by the end of this year, our overriding focus in the second half of 2024 is to generate additional data to facilitate strategic dialogue with our partners and Gen regarding potential next steps for the program. And the obvious next step, if the data supports it, of course, is to move from phase 1a to phase 1b. So, you know, we're currently enrolling, of course, additional patients with pancreatic cancer to continue to more fully explore that promising initial signal.

Speaker Change: Yeah, thanks, Malcolm. So again, with regards to our goal for an update by the end of this year.

Malcolm Kuno: You know, our overriding focus in the second half of 2024 is to...

Malcolm Kuno: generate additional data.

Malcolm Kuno: to facilitate strategic dialogue with our partner and in regarding potential next steps for the program and the obvious next step.

Sean Mccarthy: So, you know, we're currently enrolling, of course, additional patients in pancreatic cancer to continue to more fully explore that promising initial signal. And so I would say that, you know, as we reach the end of 2024, I would hope that we'd have a reasonable number of patients enrolled in pancreatic. Have a much better sense of the overall profile of the activity of the drug in that tumor type. We're also prioritizing enrollment in head and neck and also in non-small cell lung. And in those two indications, you know, we'd really enrolled very few patients when we gave the update in May.

Speaker Change: If the data supports it, of course, is to move from phase one to eight to phase one B.

Sean Mccarthy: And based on this progress, we remain on track to share initial data for CX-2051 in the first half of 2025.

Sean Mccarthy: And so I would say that, you know, as we reach the end of 2024, I would hope that we'd have a reasonable number of patients enrolled in pancreatic cancer to have a much better sense of the overall profile of the activity of the drug in that tumor type. We're also prioritizing enrollment in head and neck, and also in non-small cell lung. And in those two indications, you know, we really enrolled very few patients when we gave the update in May.

Speaker Change: So, you know, we're currently enrolling, of course, additional patients.

Speaker Change: in pancreatic cancer to continue to more fully explore.

Speaker Change: that promising initial signal. And so I would say that, you know, as we reach the end of 2024, I would hope that we'd have a reasonable number of patients enrolled in pancreatics, have a much better sense of the overall profile of the activity of the drug in that tumor type.

Speaker Change: We're also prioritizing enrollment in head and neck, and also in non-small cell lung. And in those two indications, we've really enrolled very few patients.

Sean Mccarthy: Now, turning to our third clinical program, CX-801, which is our Julie Mask Interferred Alpha 2B Pro body cytokines. We're excited about CX-801 as a foundational immunomacology agent with potential for activity across multiple tumor types, including those that are insensitive to current immunomacology therapies. Interferred is a compelling and differentiated opportunity for a mass cytokine for two key reasons.

Speaker Change: When we gave the update in May and so there we're looking to enroll additional patients to really look for an additional signal in those two tumor types.

Sean Mccarthy: And so there we're looking to enroll additional patients to really look for an additional signal in those two tumor types. And that would be our goal by the end of this year as well. So, and again, just to be clear in terms of, you know, our overriding objective, generate data, meet with Amgen, have that strategic dialogue, define phase 1b strategy, again, should the data support that, and most likely give a strategic update on the program by the end of the year with the data that underpins that update, more likely than not being presented at a venue TBD in 2025.

Sean Mccarthy: So, and again, just to be clear in terms of, you know, our overriding objective, generate data, meet with AMGN, have that strategic dialogue, define phase one B strategy, again, should the data support that, and most likely give a strategic update on the program by the end of the year, with the data that underpins that update, more likely than not being presented at a venue, TBD in 2025.

Speaker Change: and that would be our goal by the end of this year as well. So, and again, just to be clear, in terms of, you know, our overriding objective, generate data, meet with Amgen, have that strategic dialogue, define phase one, be strategy, again, should the data support that?

Sean Mccarthy: First, the biology of Inspiron is unique in that it has been shown to directly kill tumor cells, and Inspiron also increases adjutant presentation to activate T cells, making it an ideal mechanism for combination with checkpoints inhibition. Secondly, as a previously approved cancer therapy, Inspiron has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD1. The use of Inspiron and its broader development as a systemic therapy has been limited, however, due to systemic toxicities.

Speaker Change: and most likely give a strategic update on the program by the end of the year with the data that underpins that update, more likely than not being presented at a venue TBD in 2025.

Sean Mccarthy: Our preclinical data for CX-801, most recently presented at 60-2023, demonstrates synergy for our massed Inspiron Alpha with PD1 inhibition, both in terms of anti-tumor activity and activation of the systemic activity of our massed Inspiron, is significantly reduced, and overall tolerability is markedly improved compared to the unmassed cytokine in animal models.

Malcolm Kuno: Great. Thank you so much. You're very welcome. Thank you.

Landon Mitchell Kapoor: Thank you. Once again, that's star 11 for questions. One moment for our next question. Our next question comes from Landon Mitchell Kapoor from H.C. Wainwright. Your line is open.

Unknown Executive: Once again, that's Star 101 for questions. One moment for our next question.

Speaker Change: Great, thank you so much.

Speaker Change: You're very welcome.

Speaker Change: Thank you. Once again, let's start one-one for questions. One moment for our next question.

Linda Mitchell Kapoor: Our next question comes from Linda Mitchell Kapoor from H.C. Wainwright. Elaine is open.

Landon Mitchell Kapoor: Good afternoon, this is Dan on behalf of Mitch. Thanks for taking our questions and congratulations on the promotion, Chris. I apologize if my questions are redundant. You're welcome. I hopped from another call. We were wondering, given the context of the positive responses you've demonstrated in pancreatic cancer, what response rate or duration of response would be considered meaningful in future updates?

Speaker Change: Our next question comes from Mitchell Kapoor from H.C. Wainwright. Your line is open.

Linda Mitchell Kapoor: Good afternoon.

Linda Mitchell Kapoor: This is Dan on for Mitch.

Linda Mitchell Kapoor: Thanks for taking our questions, and congratulations on the promotion, Chris. I apologize. Thank you. My questions are redundant. I, you're welcome. I hopped from another call.

Speaker Change: Good afternoon, this is Dan on for Mitch. Thanks for taking our questions and congratulations on the promotion, Chris.

Sean Mccarthy: We were wondering, given the context of the positive responses, you've demonstrated in pain-creatic cancer, what response rate or duration of response would be considered meaningful in future updates? Yeah, so regarding, thanks for the question, regarding pain-creatic, I think we're all aware of just how, you know, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the therapy is available for patients off the front line. And, you know, in the second line setting, you're seeing activity of, you know, principally, chemo regimens with, you know, single-digit response rates.

Dan: I apologize if my questions are redundant, you're welcome, I hopped from another call. We were wondering, given the context of the positive responses you've demonstrated in pancreatic cancer, what response rate or duration of response would be considered meaningful in future updates? Thank you.

Sean Mccarthy: Yeah, so regarding pancreatic cancer, I think we're all aware of just how, you know, the dearth of, you know, therapies available for patients off the front line. And, you know, in the second line setting, you're seeing activity of principally chemo regimens with single-digit response rates. So these are patients that are in, you know, tough shape, with very few options. And quite frankly, we think that bar is quite low, unfortunately, given the current state of treatment for pancreatic cancer.

Sean Mccarthy: Our phase one dotescalation study is now open and our first clinical site has been activated. This study will evaluate safety and signs of clinical activity for CX-801 as a monotherapy and in combination with ketruder under a collaboration and supply agreement that we recently executed with Merck.

Speaker Change: Yeah, so regarding, thanks for the question, regarding pancreatic, I think we're all aware of just how, you know, the dearth of, you know, therapies available for patients off the front line.

Speaker Change: And, you know, in the second-line setting, you're seeing activity of principally chemoregimens with single-digit response rates. So, these are patients that are in, you know, tough shape, very few options.

Sean Mccarthy: So, these are patients that are in, you know, tough shape, very few options. and we're quite frankly, we think that bar is quite low. You know, unfortunately, given the current state of treatment of pancreatic cancer. So that's one of the many reasons that we've been really excited about this initial signal in pancreatic that we're in the midst of firming up with additional enrollment as we move into the second half of the year.

Sean Mccarthy: We anticipate initial data for CX-801 in the second half of 2025.

Sean Mccarthy: and we're quite frankly, we think that bar is quite low. Unfortunately, given the current statement of pancreatic cancer, so that's one of the many reasons that we've been really excited about this initial signal.

Sean Mccarthy: So that's one of the many reasons that we've been really excited about this initial signal in pancreatic cancer and that we're in the midst of firming up with additional enrollment as we move into the second half of the year.

Sean Mccarthy: in Pancreatic that we're in the midst of firming up with additional enrollment as we move into the second half of the year.

Landon Mitchell Kapoor: Awesome. If I could ask a follow-up question, do you expect to see any tolerability differences with 2.0.5.1 given the variability in IHC EPCAM expression?

Linda Mitchell Kapoor: Awesome.

Sean Mccarthy: If I could ask a follow-up, do you expect to see any tolerability differences with 2051 given the variability in IHC Epcam expression? I'm sorry, could you repeat the question? Do you expect to see tolerability differences with 2051 given the variability in IHC Epcam expression in the difference in Epcam expression between individuals? Well, obviously, very early in our clinical exploration of 2051, we're very pleased to have, in very short order, already navigated into the third cohort in the phase one dose escalation, and we're on track for initial data in the first half of next year. Epcam is to us a highly attractive target, as we've had for a year.

Speaker Change: Awesome. If I could ask you to follow up, do you expect to see any taller ability differences with two-year or five-one given the variability in ICCF cam expression?

Landon Mitchell Kapoor: I'm sorry, could you repeat the question?

Landon Mitchell Kapoor: Do you expect to see tolerability differences with 2.0.5.1 given the variability in IHC EPCAM expression and the difference in EPCAM expression between individuals?

Speaker Change: I'm sorry, could you repeat the question?

Landon Mitchell Kapoor: Do you expect to see tolerability differences with 205-1 given the variability in IHC Epcam Expression in the difference in Epcam Expression between individuals?

Sean Mccarthy: Well, we're obviously very early in our clinical exploration of 2051, and we're very pleased to have, in, you know, very short order, already navigated into the third cohort in the phase one dose escalation. And, you know, we're on track for initial data in the first half of next year.

Speaker Change: Well, we're obviously very early in our clinical exploration of 2051. We're very pleased to have

Speaker Change: in, you know, very short order already have navigated into the third cohort in the phase one dose escalation and, you know, we're on track for initial data in first half of next year, [inaudible]

Christopher Ogden: With that, let me hand over to Chris to provide an update on our finances. Thank you, Sean. It is a privilege to be part of the CytomX team and I look forward to helping lead the company towards multiple new treatment options for patients over the long term.

Sean Mccarthy: Epcam is, to us, a highly attractive target, and has been for a long time because of just how high its expression is in so many tumor types. And its expression is actually pretty consistent, particularly in colorectal, where we're focusing enrollment in phase one. In CRC, Epcam is expressed at IC3 plus in the majority of patients, and that's actually allowing us to not need to select patients for enrollment in the phase one

Sean Mccarthy: is to us a highly attractive target, has been for a long time because of just how

Sean Mccarthy: It's expression is in so many tumor types, and its expression is actually pretty consistent, particularly in colorectal, where we're focusing enrollment in phase one. In CRC, Epcam is expressed at IHC 3 plus in the majority of patients, and that's actually allowing us to not need to select patients for enrollment in the phase one study. So, in terms of the expression in normal tissues, there's a fair amount of Epcam in normal tissues, particularly in also in the GI tract. It can be heterogeneous, but I think we'll have to see how that plays out in the clinic.

Speaker Change: Hi, it's expression is in so many tumor types, and its expression is actually pretty consistent, particularly in colorectal, where we're focusing enrollment in phase one, in CRC, Epcambers, expressed that I see three plus.

Christopher Ogden: Now, turning to the second quarter results, I am pleased to be able to share an update on our financials with everyone today. CytomX finished the second quarter of 2024 with 137 million in cash, cash equivalence and investments versus 150 million in cash at the end of the first quarter of 2024. We expect our cash balance will fund the operations of the company to the end of 2025. Also, as a reminder, this cash guidance does not assume any additional milestones from existing collaborations or any new business development.

Sean Mccarthy: in the majority of patients and that's actually allowing us to not need to select patients.

Sean Mccarthy: So, in terms of the expression in normal tissues, there's a fair amount of Epcam in normal tissues, particularly in the GI tract. It can be heterogeneous, but I think we'll have to see how that plays out in the clinic. But so far, so good, as we're into our third cohort.

Sean Mccarthy: for Enrollment in the Phase 1 Study. So, in terms of the expression in normal tissues, there's a fair amount of EpCAM in normal tissues, particularly also in the GI tract.

Sean Mccarthy: But so far, so good as we're into our third cohort.

Sean Mccarthy: It can be heterogeneous, but I think we'll have to see how that plays out in the clinic. So far so good as we're into our third cohort.

Linda Mitchell Kapoor: Awesome, thank you so much. You're welcome. Thank you.

Landon Mitchell Kapoor: Awesome! Thank you so much.

Christopher Ogden: Operationally, we continue to be focused on controlling costs and disciplined capital allocation investing behind the clinical progression of our lead pipeline programs. Now, moving on to revenue and operating expenses for the quarter. For the second quarter of 2024, revenue was 25.1 million compared to 24.7 million in the second quarter of 2023. Operating expenses for the second quarter were 33.6 million. R&D expenses were 25.2 million in the second quarter of 2024 and increased a 4.5 million versus Q2 2023, driven by investments in our clinical pipeline. G&A expenses increased by 1 million during the three months ended June 30, 2024 to 8.4 million compared to 7.4 million for the course finding period in 2023.

Operator: Thank you. I'm not showing any further questions in the queue. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Unknown Executive: I'm not sure I need further questions in the queue.

Operator: Awesome, thank you so much.

Speaker Change: You're welcome.

Operator: Thank you. I'm not showing any further questions in the queue. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO for closure remarks.

Sean Mccarthy: I want thanks very much and thanks everyone for tuning in today. We're really excited about the progress we've made so far this year at Siteomics and we're looking forward to a busy second half and so reporting on additional progress as the year goes on.

Sean Mccarthy: Thanks very much, and thanks, everyone, for tuning in today. We're really excited about the progress we've made so far this year at CytomX, and we're looking forward to a busy second half and to reporting on additional progress as the year goes on. So have a great rest of the day.

Sean Mccarthy: Thanks very much, and thanks, everyone, for tuning in today. We're really excited about the progress we've made so far this year at CytomX.

Sean Mccarthy: We're looking forward to a busy second half and to reporting on additional progress as the year goes on. So have a great rest of the day.

Unknown Executive: So have a great rest of the day.

Unknown Executive: Thank you for your participation in today's conference. This doesn't include the program. You may know it as a connect.

Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.

Unknown Executive: Everyone have a great day.

Operator: Thank you for your participation in today's conference. This doesn't include the program you may now disconnect. Everyone have a great day.

Sean Mccarthy: Now, I'll turn the call back to Sean for closing remarks.

Sean Mccarthy: Siteomics continues to prosecute a multi-modality strategy with each of CS904, CS2051 and CS801 being well-positioned for new clinical datasets over the next 18 months. Moreover, masking strategies, as exemplified by the Pro Body Therapeutic Platform, were growing strategic interest in the biopharma R&D area, and CytomX remains a recognized leader having created this field.

Sean Mccarthy: In conclusion here at CytomX we remain highly committed and focused on creating innovative treatments for people living with cancer, and we believe our Pro Body Pipeline has the potential to deliver safer, more effective therapies.

Sean Mccarthy: I want to sincerely thank the patients who join our studies, their families, and our team for helping to drive our mission forward.

Sean Mccarthy: Etzer Darout from BML Capital Markets. Your line is open. Great. Thanks for taking a question. Just a quick one on CX904. If you know you had any more insights into sort of the correlation between efficacy and EGFR expression, and what you know could be driving the activity that you're seeing in pancreatic cancer, and maybe just remind us for CX904. Can you discuss sort of the venue if you kind of give in some thoughts into sort of the venue where you'll be presenting this update on by your end?

Sean Mccarthy: Thanks. Yeah, hi. Thanks for the questions. So we're considering to look at EGFR and how it relates to activity for CX904. As we mentioned, pancreatic cancer, like many others, expresses EGFR more than 90% of pancreatic ductal adenocrossenoma expresses EGFR. So that's clearly relates to the activity that we're seeing. We were thinking in that too, as to specific correlations between target level and response. I think that remains to be determined, and I would also say that of course for T cell engages, if we look at historical data from other programs, from other other organizations, you know, these agents are quite different to functional blocking antibodies in that we wouldn't necessarily expect to require too much adegin to drive responses, but I think this is something we're still learning both for 904 and in the field of T cell engages more broadly.

Malcolm Kuno: In terms of the next update, so as we mentioned, we're planning on an update by the end of the year that could take the form of a strategic update in terms of next steps for the program with actual data that underpins that strategic update, which will of course include dialogue with Amgen with that data coming at a future date at a venue to be determined. So no additional colour on that at this time. Great. Thank you. One moment for our next question.

Malcolm Kuno: And our next question, conflina Malcolm Kuno from KPM. Your line is open. Hi, thank you for taking the question. This is Malcolm on from Anupam Rama. So you talked about this of the 904 update at the end of year. How should you think about the size of maybe the data that we may receive and then given that you saw in a signal earlier this year, how are you thinking about prioritizing indications? Yeah, thanks Malcolm.

Sean Mccarthy: So again, with regard to, you know, our goal for an update by the end of this year, you know, our our overriding focus in the second half of 2024 is to generate additional data to facilitate strategic dialogue with our partner and then regarding potential next steps with the program and the obvious next step if the data supports it, of course, is to move from phase one A to phase one B. So, you know, we're currently enrolling, of course, additional patients in pancreatic cancer to continue to more fully explore that promising initial signal.

Sean Mccarthy: And so I would say that, you know, as we reach the end of 2024, I would hope that we'd have a reasonable number of patients enrolled in pancreatic. Have a much better sense of the overall profile of the activity of the drug in that tumor type. We're also prioritizing enrollment in head and neck and also in non-small cell lung. And in those two indications, you know, we'd really enrolled very few patients when we gave the update in May. And so there we're looking to enroll additional patients to really look for an additional signal in those two tumor types. And that would be our goal by the end of this year as well.

Linda Mitchell Kapoor: Our next question comes from Linda Mitchell Kapoor from H.C. Wainwright.

Linda Mitchell Kapoor: Elaine is open. Good afternoon. This is Dan on for Mitch. Thanks for taking our questions and congratulations on the promotion, Chris. I apologize. Thank you. My questions are redundant. I, you're welcome. I hopped from another call. We were wondering, given the context of the positive responses, you've demonstrated in pain-creatic cancer, what response rate or duration of response would be considered meaningful in future updates? Yeah, so regarding, thanks for the question, regarding pain-creatic, I think we're all aware of just how, you know, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the therapy is available for patients off the front line.

Linda Mitchell Kapoor: And, you know, in the second line setting, you're seeing activity of, you know, principally, chemo regimens with, you know, single-digit response rates. So, these are patients that are in, you know, tough shape, very few options, and we're quite frankly, we think that bar is quite low. You know, unfortunately, given the current state of treatment of pancreatic cancer.

Sean Mccarthy: So that's one of the many reasons that we've been really excited about this initial signal in pancreatic that we're in the midst of firming up with additional enrollment as we move into the second half of the year. Awesome. If I could ask a follow-up, do you expect to see any tolerability differences with 2051 given the variability in IHC Epcam expression? I'm sorry, could you repeat the question? Do you expect to see tolerability differences with 2051 given the variability in IHC Epcam expression in the difference in Epcam expression between individuals?

Sean Mccarthy: Well, obviously very early in our clinical exploration of 2051, we're very pleased to have in very short order already have navigated into the third cohort in the phase one dose escalation and we're on track for initial data in first half of next year. Epcam is to us a highly attractive target as we've had for a year. It's expression is in so many tumor types and it's expression is actually pretty consistent, particularly in colorectal where we're focusing enrollment in phase one.

Sean Mccarthy: In CRC, Epcam is expressed at IHC 3 plus in the majority of patients and that's actually allowing us to not need to select patients for enrollment in the phase one study. So in terms of the expression in normal tissues, there's a fair amount of Epcam in normal tissues, particularly in also in the GI tract. It can be heterogeneous but I think we'll have to see how that plays out in the clinic. But so far so good as we're into our third cohort. Awesome, thank you so much. You're welcome. Thank you.

Sean Mccarthy: I'm not sure I need further questions in the queue. I want thanks very much and thanks everyone for tuning in today. We're really excited about the progress we've made so far this year at siteomics and we're looking forward to a busy second half and so reporting on additional progress as the year goes on. So have a great rest of the day.

Unknown Executive: Thank you for your participation in today's conference.

Unknown Executive: This doesn't include the program. You may know it as a connect.

Unknown Executive: Everyone have a great day.

Q2 2024 CytomX Therapeutics Inc Earnings Call

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