CX-2051 Clinical Trial Results - CX-2051 demonstrated a confirmed Overall Response Rate (ORR) of 28% in patients with metastatic Colorectal Cancer (mCRC) [15, 31] - A higher ORR of 43% was observed at the 10 mg/kg dose [31] - The Disease Control Rate (DCR) was 94% in patients treated with 7.2-10 mg/kg of CX-2051 [15, 33] - Preliminary median Progression-Free Survival (PFS) was 5.8 months [15, 36] Safety and Tolerability - The Phase 1 study included 25 safety-evaluable patients treated with doses ranging from 2.4 to 10 mg/kg [28, 30] - Most Treatment-Related Adverse Events (TRAEs) were manageable and reversible, with no Grade 4-5 TRAEs reported [45] - In patients treated with 7.2-10 mg/kg, the most frequent TRAEs included diarrhea (78.3%), nausea (47.8%), and vomiting (34.8%) [45] - Serious Adverse Events occurred in 21.7% of patients [45] Future Development - Phase 1 dose expansions are underway in late-line mCRC [54, 56] - The company plans to initiate a Phase 2 study in the first half of 2026 [54]

Financials & Organization - The company had approximately $101 million in cash balance as of year-end 2024, which is expected to fund operations into Q2 2026, excluding potential milestones or new business development[6] - The company's organization consists of approximately 70 employees with integrated R&D capabilities[6] Clinical Pipeline (CX-2051) - CX-2051 (EpCAM PROBODY® Topo-1 ADC) is being developed for advanced CRC, with initial Phase 1 data expected in the first half of 2025 and determination of Phase 1b doses[7, 8] - Over 90% of CRC cases are estimated to have high EpCAM expression, making it a relevant target for CX-2051[32, 33] - In preclinical models, CX-2051 demonstrated >100x masking efficiency by ELISA and equivalent preclinical activity to deruxtecan (DXd) in irinotecan-resistant CRC models[22, 25] Clinical Pipeline (CX-801) - CX-801 (PROBODY® IFN-α2b) is being developed for advanced melanoma, with initial Phase 1 translational & biomarker data expected in the second half of 2025, and initiation of Keytruda® combination[7, 8] - Preclinical data suggests CX-801 has synergistic activity with PD-1 inhibitors and enhanced safety compared to unmasked IFNα2b[55] - CX-801 demonstrated 1000X masking efficiency based on preclinical models[54] Strategic Focus - The company is focused on addressing major unmet needs in oncology with its PROBODY® pipeline[4, 71] - The company plans to determine Phase 1b doses for potential CRC expansions and evaluate strategies for CRC combinations and additional tumor types for CX-2051[47, 72]

Summary of the Conference Call Company and Industry - **Company**: Atomic Therapeutics - **Industry**: Biotechnology, specifically focusing on oncology and cancer treatment Key Points and Arguments 1. **Introduction of APKAN ADC**: Atomic Therapeutics presented data on CX-2051, a Probody ADC targeting EpCAM, which shows potential in treating metastatic colorectal cancer (CRC) and other cancer types [4][5] 2. **Clinical Data Highlights**: - 25 patients treated with a confirmed overall response rate (ORR) of 28% across 18 efficacy evaluable patients, with a 43% ORR at the highest dose of 10 mg/kg [9] - Median progression-free survival (PFS) of 5.8 months, significantly higher than the current standard of care [10] - Disease control rate of 94% across all measures [10] 3. **Safety Profile**: - The drug demonstrated minimal on-target toxicity, which is a significant concern with EpCAM-targeting therapies due to its expression in normal tissues [12][14] - Anticipated payload toxicities were manageable, with low rates of cytopenias and moderate gastrointestinal toxicity [15][17] 4. **Expansion of Clinical Trials**: Plans to expand patient cohorts at dose levels 7.2, 8.6, and 10 mg/kg to 20 patients each by the end of the year, with a dataset expected in Q1 2026 [21][22] 5. **Regulatory Strategy**: The company aims for accelerated approval in late-line metastatic CRC, with ambitions to move into earlier treatment lines [24][25][28] 6. **Market Opportunity**: - The fourth-line CRC market is estimated to have around 15,000 treatable patients annually in the U.S., with significant revenue potential demonstrated by Fruquintinib's sales [35] - The overall market for metastatic CRC across multiple lines of treatment is approximately 150,000 patients [37] 7. **Future Development Plans**: - The company is considering combination studies with bevacizumab and exploring opportunities in other solid tumors beyond CRC [40][42] - A second drug, CX-801, is in Phase 1 trials, focusing on melanoma in combination with PD-1 inhibitors [45][48] 8. **Financial Position**: The company recently completed a financing round, providing a cash runway into Q2 2027, ensuring funding for ongoing clinical trials [52] Other Important Content - **Technological Innovation**: The Probody masking platform is highlighted as a key differentiator, allowing for targeted therapy with reduced toxicity [12][14] - **Investor Interest**: Positive investor feedback has been noted following the data release, indicating strong market confidence in the drug's potential [10][11] - **Long-term Vision**: The company envisions CX-2051 as a disruptive treatment option that could replace systemic chemotherapy in earlier lines of CRC treatment [26][30]

Company Overview - CytomX Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on oncology, developing novel conditionally activated, masked biologics aimed at localized tumor treatment [3] - The company utilizes its PROBODY therapeutic platform to create safer and more effective cancer therapies [3] - CytomX's pipeline includes therapeutic candidates such as CX-2051 and CX-801, targeting various cancer types [3] Pipeline Details - CX-2051 is a masked, conditionally activated antibody-drug conjugate (ADC) targeting epithelial cell adhesion molecule (EpCAM), with potential applications in multiple EpCAM-expressing epithelial cancers, including colorectal cancer (CRC) [3] - CX-801 is a masked interferon alpha-2b PROBODY cytokine, applicable in both immuno-oncology sensitive and insensitive tumors [3] - The company has established strategic collaborations with major oncology leaders including Amgen, Astellas, Bristol Myers Squibb, Regeneron, and Moderna [3] Upcoming Events - Sean McCarthy, CEO and Chairman of CytomX, will participate in a fireside chat at the Jefferies Global Healthcare Conference on June 5, 2025, at 2:35 p.m. ET [1] - A live webcast of the presentation will be available on CytomX's website, and management will hold one-on-one meetings with registered investors at the conference [2]

Core Insights - CytomX Therapeutics has initiated dosing of the first patient with CX-801 in combination with KEYTRUDA® in a Phase 1 study for metastatic melanoma, marking a significant step in their clinical development efforts [1][3][4] Company Overview - CytomX Therapeutics is a clinical-stage biopharmaceutical company focused on developing conditionally activated, masked biologics aimed at localized tumor treatment [5] - The company utilizes its proprietary PROBODY® therapeutic platform to create safer and more effective cancer therapies, with a pipeline that includes CX-2051 and CX-801 [5] Product Details - CX-801 is a dually masked interferon alpha-2b PROBODY® cytokine designed to enhance immune stimulation while minimizing systemic toxicities associated with traditional interferon therapies [2][5] - The combination of CX-801 with KEYTRUDA® aims to address the unmet medical needs of patients with PD-1 refractory melanoma [4] Clinical Development - The Phase 1 dose escalation study of CX-801 has commenced after successful clearance of initial monotherapy cohorts, indicating progress in the clinical trial process [3] - Initial translational and biomarker data from the study is expected in the second half of 2025, which will provide insights into the therapy's efficacy [4]

Group 1 - CytomX Therapeutics is a biotech company focused on developing novel immunotherapy approaches for various forms of cancer [1] - The company has received a bullish sentiment from analysts, indicating positive expectations for its future performance [1] Group 2 - The analyst has a PhD in biochemistry and extensive experience in analyzing clinical trials and biotech companies, which adds credibility to the insights provided [1] - The mission of the analyst is to educate investors on the science behind biotech businesses to help them make informed decisions [1]

Core Insights - CytomX Therapeutics announced positive interim Phase 1 clinical data for CX-2051 in advanced colorectal cancer [3] - The company secured a $100 million financing from a leading group of healthcare investors [3] Financial Results - The company released its first quarter 2025 financial results alongside the announcement of the Phase 1 data [3] Clinical Development - The focus of the call was primarily on the Phase 1 data for CX-2051, indicating significant progress in the clinical pipeline [3]

Core Insights - CytomX Therapeutics, Inc. experienced a significant stock price increase of 94.46% following the announcement of interim Phase 1 data for its EpCAM PROBODY ADC candidate, CX-2051, in advanced colorectal cancer [1] Clinical Data Summary - As of April 7, 25 advanced metastatic colorectal cancer patients were treated with CX-2051 across five dose levels, administered every three weeks [1] - A confirmed partial overall response rate (ORR) of 28% was observed, with 5 out of 18 patients achieving this response [2] - The median progression-free survival was reported at 5.8 months, with 10 out of 18 patients remaining on study treatment at the data cutoff [3] - CX-2051 was generally well-tolerated, with manageable adverse events and no dose-limiting toxicities observed; most treatment-related adverse events were Grade 1 or Grade 2 in severity [3] - The company has initiated dose expansions at 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg, with plans to enroll 20 patients at each level to determine the recommended Phase 2 dose [3] - Additional Phase 1 data for CX-2051 monotherapy is expected by Q1 2026, with a Phase 2 study planned for the first half of 2026 [3] Future Development Plans - CytomX plans to initiate combination studies of CX-2051 in earlier lines of colorectal cancer in 2026 [4] - The company also aims to evaluate CX-2051 in non-colorectal, EpCAM-expressing tumor indications, with potential Phase 1b study initiation in 2026 [4] Financial Overview - CytomX priced an underwritten offering of approximately 76.92 million shares at $1.30 per share, raising $100 million in gross proceeds [4] - Focused clinical development priorities and cost reductions have extended the company's cash runway into Q2 2026, ending the quarter with $79.9 million in cash, cash equivalents, and investments [5]

Financial Data and Key Metrics Changes - The company announced a financing of $100 million with a leading group of healthcare investors, which positions it well for future developments [3][7] - Positive interim Phase I data for CX-2051 in advanced colorectal cancer was shared, indicating a 28% confirmed overall response rate and a 94% disease control rate [11][12] Business Line Data and Key Metrics Changes - CX-2051, an antibody-drug conjugate targeting EpCAM, has shown robust anticancer activity in metastatic colorectal cancer, with a preliminary progression-free survival of 5.8 months [11][27] - The safety profile of CX-2051 is favorable, with no dose-limiting toxicities observed during dose escalation [12][31] Market Data and Key Metrics Changes - Colorectal cancer is a significant global health issue, with approximately 1.9 million patients diagnosed annually, expected to rise to over 3 million in the coming decades [9] - The current five-year survival rate for metastatic colorectal cancer is only 13%, highlighting the unmet medical need in this area [9] Company Strategy and Development Direction - The company aims to establish CX-2051 as a new standard of care in late-line colorectal cancer and is exploring opportunities to advance the drug into earlier lines of therapy [38][39] - There is potential for CX-2051 to be a pan-tumor target, expanding its application beyond colorectal cancer [40] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the efficacy of CX-2051 and its potential to transform treatment paradigms in colorectal cancer [39][40] - The company is focused on generating data from ongoing dose expansions and plans to initiate Phase II studies in the first half of 2026 [35][49] Other Important Information - The company has validated that EpCAM is present at high levels in all patients tested, supporting the broad applicability of CX-2051 [12][24] - The pharmacokinetics of CX-2051 are behaving as expected for an antibody-drug conjugate, with a half-life of approximately six days [34] Q&A Session Summary Question: Differences in patient responses between stable disease and responders - Management noted that the overall activity level in an unselected patient population is impressive and that they will continue to analyze patient characteristics that may influence response [44][46] Question: Current development strategy for pivotal endpoints - The company is focused on generating data from three expansion cohorts and will discuss the optimal path forward for Phase II with regulatory authorities [47][49] Question: Management of serious adverse events - The safety profile is encouraging, and the serious adverse events reported are consistent with the overall adverse event profile [52][54] Question: Plans for Phase II study and potential design - Discussions with regulatory authorities regarding accelerated development and comparator arms are ongoing, with a focus on demonstrating the drug's potential against current standards of care [61][62] Question: Evidence of EpCAM expression in earlier stage patients - Management expressed confidence in EpCAM's expression throughout the natural history of colorectal cancer, supporting its use in earlier treatment lines [71][72] Question: Plans for higher dosing based on emerging signals - The company is excited about the current response rates and is not currently expanding upper dose levels but will present data from them in future updates [74][75]

Financial Data and Key Metrics Changes - CytomX Therapeutics announced a financing of $100 million with a leading group of healthcare investors, which underscores the confidence in the company's progress and potential [3][7] - The company reported a 28% confirmed overall response rate and a 94% disease control rate for CX-2051 in metastatic colorectal cancer, with a preliminary progression-free survival of 5.8 months [11][26] Business Line Data and Key Metrics Changes - CX-2051, an antibody-drug conjugate targeting EpCAM, has shown promising results in a Phase I clinical trial focused exclusively on metastatic colorectal cancer [11][19] - The trial included a heavily pretreated patient population, with a median of four prior lines of therapy, indicating the drug's potential effectiveness in late-line treatment settings [21] Market Data and Key Metrics Changes - Colorectal cancer is a significant global health issue, with approximately 1.9 million new cases diagnosed annually, expected to rise to over 3 million in the coming decades [7][8] - The current five-year survival rate for metastatic colorectal cancer is only 13%, highlighting the urgent need for innovative treatment options [8] Company Strategy and Development Direction - The company aims to position CX-2051 as a new standard of care in late-line colorectal cancer treatment, with plans to expand its use into earlier lines of therapy [36][37] - There is a vision to explore CX-2051's potential in other solid tumors, leveraging the high expression of EpCAM across various cancer types [37][38] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the drug's performance and its potential to transform colorectal cancer treatment, emphasizing the inadequacy of current standard therapies [36][37] - The company plans to generate additional data from ongoing expansions and engage with regulatory authorities to expedite the development process [48][62] Other Important Information - The safety profile of CX-2051 has been favorable, with no dose-limiting toxicities observed to date, and the adverse events reported were manageable and reversible [30][31] - The company is exploring prophylactic strategies to manage gastrointestinal toxicities associated with the treatment [66] Q&A Session Summary Question: What differences are seen between stable disease and responders in terms of baseline characteristics? - Management noted the overall impressive disease control rate and response rate, indicating that they will continue to analyze patient characteristics that may influence outcomes [44][45] Question: What is the current development strategy for pivotal endpoints and moving into earlier lines? - The focus is on generating data from expansion cohorts, with plans to discuss optimal paths for Phase II and potentially Phase III trials with regulatory authorities [48][62] Question: Can you provide details on the management of serious adverse events? - The safety profile is encouraging, and while specific patient details cannot be disclosed, the adverse events reported align with the overall profile [54][55] Question: Are there plans for accelerated development or breakthrough designations? - Discussions with regulatory authorities are anticipated, and the expansion data will be crucial for these conversations [62] Question: Is there evidence of high EpCAM expression in earlier stage patients? - EpCAM is well-established as a CRC target, and its expression is consistent throughout the disease's natural history, supporting its use in earlier treatment lines [71][72] Question: Will higher dosing be considered based on emerging signals? - While the current dose levels are being expanded, the company is cautious about escalating doses without observing dose-limiting toxicities [75][76]