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- **Q3 2025 Financial & Clinical Updates:**
  - **Key Takeaways:**
    - **Positive Clinical Momentum:**
      - **CX-2051 Phase I/II Updates:**
        - **Investor Sentiment Drivers:**
          - **Market-impacting Developments:**
            - **Clinical Trial Progress & Regulatory Updates:**
              - **Key Events:**
                - **Investor Sentiment & Market Reaction:**
                  - **Potential Impact on Share Price:**
                    - **Q3 2025 Key Developments:**
                      - **Clinical Trial Progress:**
                        - **CX-2051 Enrollment & Safety Updates:**
                          - **Loperamide Prophylaxis Reduces Diarrhea by 70%, Enabling Higher Dose Tolerability.
                          - **Competitor Activity:**
                            - **BioAtla's Bispecific Program Could Impact CytomX's Competitive Positioning.


**【Management Opening Remarks】**
- **Sean McCarthy (Chairman & CEO) highlighted the following key updates:**
- CytomX reported $143.6 million in cash as of September 30, 2025, supporting operations through Q3 2025. The company emphasized progress in CX-2051 and CX-801 clinical trials.

**【CEO & CFO Commentary】**
- **Clinical Pipeline Updates:**
  - **CX-2051 (PROBODY ADC targeting EpCAM in colorectal cancer) showed encouraging data:**
    - **Q3 2025 Key Highlights:**
      - **Financials & Clinical Progress:**
        - **Revenue & Expenses:**
          - Q3 2025 Revenue: $33.4 million (down 10% YoY due to completed BMS collaboration)
          - Operating Expenses: $21.7 million (down 25% YoY due to cost-cutting)
        - **Clinical Trial Updates:**
          - **CX-2051 Phase I/II:** 100+ patients enrolled across multiple sites.
          - **Key Data Points:**
            - **PFS at 5.8 months** vs. 2-3 months for standard therapy.
            - **Diarrhea Management:** Loperamide prophylaxis reduced Grade 3+ diarrhea rates by 70%, enabling higher dose tolerability.
        - **Q3 2025 Key Events:**
          - **Regulatory Milestones:**
            - FDA accepted the IND for CX-2051 combination with bevacizumab.
            - Initiated CX-801 (IFN-α2b PROBODY) in melanoma.
          - **Market Sentiment:**
            - Stock surged 25% on positive clinical momentum.

**【Q&A Highlights】**
- **Investor Sentiment:**
  - **Key Concerns:**
    - **Enrollment Rates:** 100% of Q3 2025's 100+ patients met the 100% enrollment target, signaling strong clinical interest.
    - **Safety & Efficacy Updates:**
      - **Diarrhea Management:** Loperamide prophylaxis reduced Grade 3+ diarrhea by 70%, enabling higher dose tolerability.
    - **Competitor Activity:**
      - **Regulatory & Market Dynamics:**
        - BioAtla's bispecific EpCAM program may impact CytomX's competitive positioning.
        - FDA interactions and regulatory strategy updates were key investor focuses.

**【Core Financial & Clinical Updates】**
- **Q3 2025 Financials & Clinical Developments:**
  - **Key Events & Market Sentiment:**
    - **Clinical Trial Progress & Regulatory Updates:**
      - **EpCAM-targeted ADCs saw significant developments that could impact CytomX's competitive landscape.
    - **Investor Sentiment & Market Reaction:**
      - **Positive Clinical Momentum:**
        - CX-2051's 5.8-month PFS vs. 2-3 months for standard therapy drove 25% stock surge.
        - Regulatory and clinical updates influenced investor decisions.


CytomX Therapeutics, Inc. (CTMX) Q3 2025 Earnings Call Transcript

- **CX-2051 Breakthrough**: 28% ORR in 4th-line CRC with 5.8-month PFS; Phase II monotherapy planned for 2026, with combination studies in earlier lines.
- **Financial Strength**: $158M cash post-$100M offering; reduced expenses (41% YoY) support runway to Q2 2027.
- **CX-801 Combination Potential**: Phase I with KEYTRUDA in melanoma; translational data in Q4 2025 to validate interferon-driven immune response.
- **Strategic Focus**: Prioritize 4th-line CRC for rapid approval, while exploring partnerships for EpCAM expansion.

**【CEO Summary Section】**
- **CX-2051 Phase I Data Highlights**: Achieved 28% confirmed ORR, 94% disease control, and 5.8 months PFS in 18 evaluable patients with metastatic CRC. Expansion cohorts at 7.2, 8.6, and 10 mg/kg are enrolling ~20 patients each, targeting 70 total patients for Q1 2026 update. Phase II monotherapy in 4th-line CRC planned for H1 2026, with potential combination studies (e.g., with bevacizumab) in earlier lines.
- **CX-801 Progress**: Initiated Phase I combination with KEYTRUDA in melanoma; monotherapy translational data (tumor biopsy analysis) expected in Q4 2025 to assess interferon-induced immune modulation. Combination safety and efficacy data anticipated in 2026.

**【CFO Financial Commentary】**
- **Financial Position**: $158.1M cash as of Q2 2025 (up from $79.9M Q1 2025) after $100M follow-on offering. Revenue $18.7M (down 25% YoY) due to completed collaborations; operating expenses $19.9M (down 41% YoY) driven by lower R&D and G&A costs. Cash runway extended to Q2 2027 without additional milestones.
- **Capital Allocation**: Focused on advancing CX-2051 and CX-801; $11.9M R&D reduction reflects prioritization of core programs. Collaborations (e.g., with Regeneron, Astellas) remain capital-efficient value drivers.

**【Q&A Highlights】**
- **CRC Strategy**: CEO emphasizes 4th-line CRC as top priority for rapid approval, though acknowledges lack of precedent for accelerated approval in CRC. Exploring combination trials (e.g., with bevacizumab) for earlier lines, with Phase II design decisions pending Phase I data.
- **EpCAM Beyond CRC**: CEO notes EpCAM's broad expression across solid tumors (e.g., lung, pancreatic, breast) and potential for partnerships to expand into other indications, though prioritizing CRC for near-term value creation.
- **Safety Monitoring**: Diarrhea (Grade 3 in ~20% of patients) is key focus; prophylactic loperamide use being optimized. CX-801 combination with KEYTRUDA expected to have manageable safety profile based on interferon masking technology.

CytomX Therapeutics (CTMX)-7 Aug 25-2025 Q2 Earnings call transcript

- **28% ORR Breakthrough**: CX-2051 achieves 28% confirmed partial responses in late-line CRC.
- **94% Disease Control**: All patients maintained stable disease or better, with 5.8-month PFS.
- **$100M Financing**: Strengthens pipeline execution for rapid 2051 approval.
- **No Dose-Limiting Toxicities**: Favorable safety profile supports earlier-line combinations.
- **Pan-Tumor Potential**: High EpCAM expression across solid tumors opens broad opportunities.

**【CEO Summary Section】**
- Introduced CX-2051 as a first-in-class EpCAM-targeting ADC for metastatic CRC.
- Highlighted Phase 1 interim data: 28% confirmed ORR, 94% DCR, 5.8-month PFS.
- Emphasized favorable safety profile with no dose-limiting toxicities.
- Announced $100M financing to accelerate development and execution.

**【CMO Clinical Data Review】**
- 18 efficacy-evaluable patients showed 5 confirmed partial responses (28% ORR).
- Disease control maintained in all patients, with 10 still on treatment (5.8-month PFS).
- EpCAM expression uniformly high across all tumor biopsies (H-scores near maximal).
- No grade 4/5 AEs or dose-limiting toxicities observed.

**【Q&A Key Points】**
- **Development Strategy**: Expanding Phase 1 cohorts to 20 patients each, targeting Q1 2026 data update.
- **Regulatory Path**: Exploring accelerated development with FDA post-expansion data.
- **Safety Management**: Implementing prophylactic loperamide for diarrhea prevention.
- **Future Plans**: Potential Phase 2/3 trial in 2026, exploring earlier-line combinations.
- **Pan-Tumor Potential**: Evaluating CX-2051 in other solid tumors with high EpCAM expression.


CytomX Therapeutics (CTMX)-12 May 25-2025 Q1 Earnings call transcript

- **Lead Program Momentum**: CX-2051 ADC in late-line CRC nearing therapeutically active doses, with H1 2025 data readout.
- **Innovative Immunotherapy**: CX-801 masked interferon alpha exceeding unmasked doses in melanoma, with combo trials planned.
- **Financial Strength**: $100.6M cash runway to Q2 2026, supporting clinical milestones with disciplined spending.
- **Strategic Partnerships**: $5M milestone from Astellas; T-cell engager discovery pipeline active with top pharma collaborators.

**【CEO Pipeline Update】**
- **CX-2051 (ADC for Colorectal Cancer)**: 
  - Enrolled late-line CRC patients (≥3 prior therapies) without preselecting EpCAM or KRAS status.
  - Currently at 7th dose level in Phase I, with safety profile supporting escalation to therapeutically active doses.
  - Expected initial data in H1 2025, focusing on safety, tumor stabilization, and potential RECIST responses.
- **CX-801 (Masked Interferon Alpha)**: 
  - Phase I study in melanoma progressing to 4th dose level, exceeding unmasked interferon's approved dose.
  - Combination with KEYTRUDA planned for H2 2025 under Merck collaboration.
  - Translational data on tumor microenvironment expected in H2 2025.
- **Partnerships**: 
  - $5M milestone from Astellas for T-cell engager candidate; ongoing discovery work with BMS, Amgen, Moderna, and Regeneron.
  - CX-904 (Amgen T-cell engager) discontinued due to prioritization shift.

**【CFO Financial Overview】**
- **Cash Position**: $100.6M as of Dec 2024, extended runway to Q2 2026 with focused capital allocation.
- **Revenue**: $138.1M (2024) vs $101.2M (2023), driven by BMS, Moderna, Astellas, and Regeneron collaborations.
- **Operating Expenses**: $113.1M (2024) vs $107.7M (2023), with $5M milestone payment for CX-2051 Phase I initiation.
- **Disciplined Spending**: Flat R&D and G&A outside milestone, reflecting strategic prioritization.

**【Q&A Highlights】**
- **CX-2051 Dose Escalation**: 7th dose level in late-line CRC; safety data and tumor activity (e.g., tumor shrinkage) to be shared in H1 2025.
- **CX-801 Combination Timing**: KEYTRUDA combo initiation expected in H2 2025, alongside translational data updates.
- **CRC Unmet Need**: Late-line CRC patients have <10% response rates to current therapies; any RECIST response would be significant.


CytomX Therapeutics (CTMX)-6 Mar 25-2024 Q4 Earnings call transcript

CytomX Therapeutics (CTMX)-7 Nov 24-2024 Q3 Earnings call transcript

CytomX Therapeutics (CTMX)-8 Aug 24-2024 Q2 Earnings call transcript

CytomX Therapeutics (CTMX)-8 May 24-2024 Q1 Earnings call transcript

- **Pipeline Momentum**: Three lead programs (CX-904, CX-2051, CX-801) advancing into Phase I trials in 2024, with CX-904 data expected H2 2024.
- **Strategic Partnerships**: $460M potential from Amgen collaboration; BMS shifting focus to T-cell engagers.
- **Financial Strength**: $175M cash balance, 31% cost reduction, and >$500M in partnership receipts.
- **Safety Profile**: CX-904 preclinical data shows >95% masked antibody circulation, reducing systemic toxicity.

**【CEO Opening Remarks】**
- CytomX highlighted its Probody platform's leadership in masking and conditional activation strategies for biologics like ADCs, T-cell engagers, and cytokines.
- Emphasized progress across three key programs: CX-904 (EGFR-CD3 T-cell engager), CX-2051 (EpCAM-targeted ADC), and CX-801 (masked interferon-alpha).
- 2024 milestones include Phase Ia data for CX-904 in H2 2024, and Phase I starts for CX-2051 and CX-801.
- Strategic partnerships with Amgen, BMS, Regeneron, and Moderna drive pipeline expansion.

**【CEO Pipeline Update】**
- **CX-904**: Phase Ia dose escalation ongoing with Amgen; targeting EGFR-positive solid tumors. Expected H2 2024 data to inform Phase Ib design. Focus on managing CRS and EGFR-mediated toxicities.
- **CX-2051**: FDA-cleared IND for EpCAM-targeted ADC; Phase I start imminent in colorectal and other EpCAM-expressing cancers. Uses camptothecin payload for potent tumor activity.
- **CX-801**: FDA-cleared IND for masked interferon-alpha; Phase I start in H1 2024 for melanoma, renal, and head/neck cancers. Seeks combination with checkpoint inhibitors.

**【Partnership Updates】**
- **Amgen Collaboration**: CX-904 co-development with $460M potential milestones and U.S. profit share. CytomX retains ex-U.S. royalties (low double to mid-teens).
- **BMS Collaboration**: Discontinuation of CTLA-4 program, but T-cell engager focus continues. Multiple new programs in pipeline.
- **New Partnerships**: Regeneron and Moderna collaborations add 12+ active discovery programs.

**【CFO Financial Summary】**
- **Cash Position**: $175M as of Q4 2023, sufficient for operations into H2 2025 without additional funding.
- **Revenue Growth**: $101.2M in 2023 (vs. $53.2M in 2022), driven by BMS collaboration and new partnerships.
- **Cost Efficiency**: R&D expenses down 31% ($111.6M to $77.3M) and G&A down 31% ($42.8M to $29.8M) year-over-year.
- **Milestone Potential**: >$500M in partnership cash receipts to date, with additional 2024-2025 milestones.

**【Q&A Highlights】**
- **CX-904 Safety**: Preclinical data shows masked antibody circulation >95%; systemic CD3 binding reduced. Dose-limiting toxicities in GLP studies were EGFR-mediated, not CRS.
- **CX-904 Timeline**: H2 2024 data will include safety, tolerability, and early efficacy signals. Phase Ib design to be finalized post-H2 update.
- **Competitive Landscape**: Probody platform's ability to reduce systemic target engagement validated by recent competitor data.


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