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- **Revenue Surges**: Q3 2025 revenue up 72.5% YoY to $27.6 million, driven by $25M J&J milestone and $1M royalties.
- **Clinical Breakthroughs**: ZW191 ADC shows 64% ORR in gynecologic cancers with favorable safety; ZW251 GPC3 ADC dosing begins.
- **Strategic Moves**: $22.7M share buyback, pipeline expansion with DLL3 trispecific T-cell engager, and J&J pasritamig Phase III milestone.
- **Upcoming Catalysts**: HERIZON-GEA-01 PFS/OS data Q4 2025, ZW191 dose optimization, and DLL3 IND filing H1 2026.

**【Leone Patterson's Presentation】**
- **Revenue Growth**: Q3 2025 revenue of $27.6 million, up 72.5% YoY, driven by a $25 million milestone from J&J for pasritamig Phase III progress and $1 million in royalties.
- **Financial Highlights**: GAAP net loss of $19.6 million (vs. $29.9M YoY), operating expenses stable at $49.7 million, and $22.7 million share repurchased under a $30 million program.
- **Pipeline Momentum**: ZW191 ADC dosing in Phase I, ZW251 GPC3 ADC first patient dosed, and ZW171 T-cell engager discontinued due to monotherapy limitations.

**【Sabeen Mekan's Clinical Update】**
- **ZW191 ADC**: 64% ORR in gynecologic cancers at 6.4-9.6 mg/kg, tolerable safety profile with no Grade 3+ AEs, and planned dose optimization in Q4 2025.
- **ZW251 ADC**: Phase I trial for hepatocellular carcinoma with DAR4 payload, targeting 100 patients globally, with enrollment underway.

**【Paul Moore's R&D Update】**
- **ADC Strategy**: Tailored ADCs with optimal D:AR and payloads (e.g., ZW191's ZB06519), discontinuation of ZW171 due to monotherapy futility, and next-gen T-cell engagers (e.g., DLL3 trispecific).
- **Preclinical Pipeline**: IND-ready NaPi2b ADC, Ly6E, and PTK7 targets, with focus on combination therapies and external partnerships.

**【Ken Galbraith's CEO Remarks】**
- **Strategic Focus**: Partnership-driven growth (e.g., J&J, Jazz), disciplined capital allocation, and $299.4 million cash balance to fund operations through 2027.
- **Shareholder Value**: Share repurchases, royalty portfolio reinvestment, and pipeline derisking via collaborations.

**【Q&A Highlights】**
- **HERIZON-GEA-01 Trial**: Jazz expanded ITT population to 920 patients, delaying PFS/OS analysis but maintaining trial integrity.
- **GPC3 ADC (ZW251)**: DAR4 design balances efficacy and safety, with potential for earlier-line use in hepatocellular carcinoma.
- **DLL3 Trispecific**: CD28 co-stimulation aims to enhance T-cell persistence, with preclinical data showing improved efficacy vs. bispecifics.
- **Zanidatamab (Jazz)**: PFS/OS data expected Q4 2025, with Jazz maintaining confidence in potential registrational success.


Zymeworks Inc. (ZYME) Q3 2025 Earnings Call Transcript

- **Revenue Growth**: Q2 2025 revenue of $48.7M (+153% YoY) driven by $20M BeOne milestone and $7.5M BMS payment.
- **Financial Health**: Net income of $2.3M vs. Q2 2024 loss; cash of $333.4M supports operations into 2027.
- **Clinical Momentum**: ZW251 IND cleared; ZW171/191 trials progressing with adaptive dosing strategies.
- **Strategic Partnerships**: Ziihera approvals in China/Europe; J&J's pasritamig shows promising safety in prostate cancer.
- **Upcoming Catalyst**: HERIZON-GEA PFS data expected Q4 2025.

**【CEO Summary Section】**
- Zymeworks' strategy focuses on platform-driven innovation and strategic partnerships to maximize asset value. Key partnerships with Jazz and BeOne for zanidatamab (Ziihera) are expected to generate royalty revenues and milestone payments.
- The company maintains a wholly owned pipeline of 6 clinical-stage ADCs and multispecific antibodies, with 100% commercial rights retained. Future collaborations aim to share risk and accelerate development while preserving long-term economics.
- Financial discipline is prioritized, with a focus on preserving cash runway and evaluating opportunities for capital allocation, including shareholder returns.

**【CFO Financial Commentary】**
- Q2 2025 total revenue: $48.7 million (vs. $19.2 million in Q2 2024), driven by $20 million milestone from BeOne for zanidatamab's China approval and $7.5 million from BMS.
- Operating expenses: $49.4 million (20% decrease vs. Q2 2024), due to reduced costs for zanidatamab and ZW220, offset by increased R&D for ZW171/191/251.
- Net income: $2.3 million (vs. net loss of $37.7 million in Q2 2024), reflecting higher revenue and lower expenses.
- Cash resources: $333.4 million as of June 30, 2025, supporting operations into H2 2027.

**【Clinical Development Updates】**
- **ZW171 (mesothelin ADC)**: Phase I trial using subcutaneous step-up dosing (4.2 µg, 12.6 µg, 38 µg) with mTPI design to identify MTD. Enrollment progressing as planned.
- **ZW191 (FRα ADC)**: Phase I trial in ovarian, endometrial, and NSCLC cancers with starting dose of 1.6 mg/kg IV. Conservative approach due to first-in-human 519 payload, with adaptive dose escalation.
- **ZW251 (GPC3 ADC)**: Received IND clearance for HCC. Designed with DAR4 payload for enhanced tolerability in liver-impaired patients, with preclinical data showing strong safety and efficacy.

**【R&D and Pipeline Updates】**
- **ZW1528 (IL-4/IL-33 bispecific)**: Preclinical data shows superior inhibition of type 2 and non-type 2 inflammation vs. monotherapies. Expected non-U.S. regulatory filing in H2 2026.
- **Ziihera (zanidatamab)**: Conditional approvals in China and Europe for second-line HER2+ BTC, with Jazz and BeOne initiating Phase II trials for GEA and BTC expansion.
- **Partnerships**: J&J's pasritamig (KLK2 TCE) shows favorable safety and early efficacy in prostate cancer; Daiichi Sankyo's DS-2243 (TCE) in Phase I for solid tumors.

**【Q&A Highlights】**
- **HERIZON-GEA Study**: Top-line PFS data expected Q4 2025; Jazz and BeOne will determine data release format. No plans to stratify by PD-L1 status in top-line results.
- **Pipeline Dosing**: ZW251 to start at higher doses due to preclinical safety; ZW191 enrollment on track for initial data in 2025/2026.
- **Partnership Strategy**: Open to collaborations across entire pipeline, prioritizing partners with complementary capabilities and global reach.


Zymeworks Inc. (ZYME) Q2 2025 Earnings Call Transcript

- **Revenue Soars 171% YoY**: Q1 2025 revenue of $27.1M driven by $17.1M in milestones and partnerships.
- **Pipeline Catalysts Abound**: Upcoming EMA decision on zanidatamab, JNJ's ASCO presentation of KLK2 T-cell engager, and ZW209 IND in H1 2026.
- **ADC & T-Cell Engager Innovation**: Ly6E ADC shows superior efficacy, PTK7 biparatopic ADC enhances payload delivery, and ZW209's CD28 co-stimulation reduces off-target activation.
- **Financial Discipline**: $321.6M cash runway into 2027 with 10% operating expense growth, balanced against partner-driven revenue streams.

**【Leone Patterson - Business & Financial Update】**
- **Revenue Growth**: Q1 2025 revenue of $27.1M vs. $10M in Q1 2024, driven by $14M milestone from GSK and $3.1M from Daiichi Sankyo.
- **Net Loss Improvement**: Net loss of $22.6M (vs. $31.7M in Q1 2024) due to higher revenue offset by 10% increase in operating expenses.
- **Cash Position**: $321.6M in cash as of March 2025, providing runway into H2 2027.
- **Pipeline Momentum**: Upcoming EMA approval decision for zanidatamab in biliary tract cancer and JNJ's ASCO presentation of KLK2 T-cell engager with $86M+ potential milestones.

**【Paul Moore - R&D Highlights】**
- **ZW209 (DLL3 T-cell engager)**: Preclinical data shows superior cytotoxicity vs. tarlatamab, with obligate CD28 co-stimulation for safety. IND submission planned for H1 2026.
- **ADC Programs**: Ly6E-targeted ADC (ZW327) demonstrates superior efficacy and tolerability; PTK7 biparatopic ADC shows enhanced internalization and cytotoxicity.
- **Clinical Trials**: ZW171 (mesothelin T-cell engager) Phase 1 trial progressing with 15+ global sites activated.

**【Ken Galbraith - Strategic Overview】**
- **Capital Allocation**: Disciplined approach to pipeline prioritization, balancing wholly-owned assets with partner-driven revenue (e.g., zanidatamab royalties up to 20%).
- **Leadership Expansion**: Appointments of Dr. Sabeen Mekan (SVP Clinical Development) and Barbara Schaeffler (SVP Clinical Ops) to strengthen clinical execution.
- **Near-Term Catalysts**: Phase 3 zanidatamab data readout in 2025, JNJ's KLK2 T-cell engager Phase 1 results at ASCO, and EMA decision on zanidatamab.

**【Q&A Key Takeaways】**
- **Zanidatamab Milestones**: Potential $86M+ from JNJ partnership and royalty tiers up to 20% of Jazz sales post-approval.
- **Internal Pipeline Capacity**: Can support ~5 internal Phase 1 programs with current infrastructure, evaluating collaborations for additional assets.
- **ADC vs. T-Cell Engager Strategy**: Target-specific optimization (e.g., DLL3 for T-cell engagers, Ly6E for ADCs) to maximize therapeutic impact.

Zymeworks Inc. (ZYME) Q1 2025 Earnings Call Transcript

- **Revenue Growth**: FY2024 revenue of $76.3M driven by $25M Jazz milestone and $8M BeiGene BLA milestone.
- **Pipeline Prioritization**: ZW251 prioritized for HCC with IND in mid-2025; ZW220 paused for potential partnerships.
- **Cash Runway**: $324.2M cash as of Q4 2024, supporting operations into H2 2027.
- **Clinical Momentum**: ZW171 and ZW191 Phase 1 trials progressing globally with tolerable profiles.
- **Autoimmune Expansion**: ZW1528 nominated for COPD, leveraging oncology immune modulation expertise.

**【Leone Patterson: Corporate & Financial Update】**
- **Revenue Performance**: FY2024 total revenue of $76.3M, driven by $25M milestone from Jazz for Ziihera FDA approval and $8M from BeiGene for zanidatamab BLA acceptance in China. Operating expenses remained stable at $213.4M, with R&D down 5% YoY due to program transfers to partners.
- **Financial Position**: $324.2M cash as of Q4 2024, providing a cash runway into H2 2027. Anticipated milestone payments from Jazz and BeiGene could extend this runway.
- **Partnership Milestones**: $14M GSK research milestone in Q1 2025 and $1.1M Ziihera net sales by Jazz in Q4 2024 highlight partner collaboration strength.

**【Paul Moore: R&D Pipeline Updates】**
- **Oncology Pipeline**: 
  - ZW251 (GPC3 ADC) prioritized for IND in mid-2025, with ZW220 (NaPi2b ADC) paused for potential partnerships.
  - ZW171 (mesothelin TCE) and ZW191 (folate receptor ADC) in global Phase 1 trials, showing tolerable profiles and early activity.
- **Autoimmune Expansion**: ZW1528 (IL-4Rα/IL-33 bispecific) nominated for COPD, leveraging oncology immune modulation expertise.

**【Kenneth Galbraith: Strategic Priorities & Q&A】**
- **Pipeline Focus**: Accelerated ZW251 development for hepatocellular carcinoma (HCC) due to unmet need and differentiated preclinical data. ZW220 remains IND-ready but delayed for resource allocation.
- **Commercial Catalysts**: Ziihera royalties from Jazz and BeiGene, with top-line HERIZON-GEA-01 data expected H2 2025.
- **Partnership Outlook**: Open to new collaborations to expand ADC and TCE pipelines, with focus on autoimmune and oncology opportunities.


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