Zymeworks Inc. (ZYME)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 revenue rose to $31.0M, up 83% year over year (vs. $16.9M in Q4 2023), while net loss was $23.5M and diluted EPS was $(0.31); net margin improved materially to -75.8% from -85.6% YoY .
• Ziihera (zanidatamab-hrii) received U.S. accelerated approval for HER2+ BTC in November 2024; initial U.S. launch generated $1.1M in Jazz net sales in Q4 with Zymeworks beginning to recognize royalties in Q4 2024 .
• Pipeline reprioritization: IND for ZW251 (GPC3 ADC) accelerated to mid-2025; preparations for ZW220 (NaPi2b ADC) paused to focus resources, while Phase 1 dose-escalation continues for ZW171 (mesothelin TCE) and ZW191 (FRα ADC) globally .
• Cash resources were $324.2M at year-end, and with anticipated regulatory milestones, management reaffirmed cash runway into 2H 2027; noted potential extension via commercial milestones and royalties from partners Jazz and BeiGene .

What Went Well and What Went Wrong

What Went Well

• U.S. approval and launch of Ziihera in HER2+ BTC; “With initial uptake in biliary tract cancer in the US, we look forward to reporting on the outcomes of pending regulatory actions in the European Union and China in 2025…” — CEO Kenneth Galbraith .
• Pipeline execution: first-in-human global studies initiated for ZW191 and ZW171; IND for ZW251 accelerated to mid-2025, signaling prioritization toward HCC opportunity .
• Monetization from partnerships: $25M milestone from Jazz (FDA approval), $8M BeiGene milestone (China BLA acceptance) and $14M GSK research milestone achieved in January 2025, demonstrating platform value .

What Went Wrong

• HERIZON-GEA-01 top-line PFS timing pushed out from Q2 2025 to 2H 2025, lengthening the timeline to a key catalyst .
• ZW220 (NaPi2b ADC) clinical start paused despite IND-ready status, reflecting resource constraints and prioritization over breadth of execution .
• Non-cash impairment ($17.3M in 2024) from discontinuation of zanidatamab zovodotin weighed on reported results; tax expense increased vs. 2023, contributing to a higher annual net loss .

Financial Results

Quarterly Performance vs. Prior Periods

Notes: Net income margin calculated from revenue and net loss in cited sources.

Operating Expense Profile

Revenue Composition (FY)

KPIs

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “Based on current operating plans, our strong financial position of $324.2 million in cash resources as of December 31, 2024, together with certain anticipated regulatory milestone payments, continues to provide an expected cash runway into the second half of 2027.” — CFO Leone Patterson .
• “We are advancing another exciting antibody-drug conjugate toward IND submission… ZW251 provides a new therapeutic modality option targeting GPC3 for hepatocellular carcinoma… we look forward to initiating a Phase 1 trial for ZW251 this year.” — CSO Paul Moore .
• “We’re extremely interested… in the entire portfolio, specifically with ZW251 in HCC… study it in dose escalation… then… in expansion cohorts… with the greatest possibility of a stronger outcome in an earlier treatment setting in combination.” — CEO Kenneth Galbraith (Q&A) .

Q&A Highlights

• ZW251 prioritization and development path: Management emphasized urgency to reach combination cohorts post dose-escalation in HCC, aiming for differentiated tolerability and early activity before expansion .
• ZW220 pause rationale: Decision driven by resource allocation and ability to accelerate ZW251 without losing momentum in ZW171/ZW191; ZW220 remains IND-ready for future initiation or partnering .
• HERIZON-GEA-01 timeline: Management deferred to Jazz guidance; enrollment on track but event accrual pushed timing to 2H 2025 .
• ZW191 linker stability and tolerability: Chosen “traditional” linker stability to enable higher dosing and better combination compatibility, citing preclinical tolerability up to 60 mg/kg (DAR-8 TOPO payload) .
• Autoimmune program (ZW1528) IND gating: IND-enabling activities underway, with 2H 2026 timing and awareness of external read-throughs (e.g., IL-33 in COPD), while remaining confident in bispecific design .

Estimates Context

• Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was unavailable at time of retrieval due to system limits; as a result, beats/misses vs consensus cannot be assessed in this recap. Once accessible, we will update comparisons to “Primary EPS Consensus Mean” and “Revenue Consensus Mean” for Q4 2024 and prior quarters.

Key Takeaways for Investors

• U.S. approval and initial launch of Ziihera create near-term royalty streams; pending EU/China decisions and 2H 2025 GEA PFS readout are major 2025 catalysts .
• Pipeline focus sharpened: acceleration of ZW251 IND to mid-2025 and pause of ZW220 signal disciplined capital allocation; expect near-term clinical dataflow from ZW171/ZW191 dose-escalation progress .
• Financial resilience: $324.2M year-end cash and reaffirmed 2H 2027 runway provide capacity to fund clinical execution; partner milestones (Jazz/BeiGene/GSK) and royalties can extend runway or fund expansion .
• Near-term trading implications: watch for EU/China BTC decisions, incremental Jazz sales and royalty disclosures, and clinical site activation updates; GEA timing shift to 2H 2025 likely tempers earlier expectations but preserves a significant mid/late-2025 event .
• Medium-term thesis: platform validation across ADCs and multispecific antibodies, growing partner monetization, and autoimmune entry (ZW1528) diversify value drivers and reduce binary risk .
• Risk monitor: regulatory timing slippage (GEA), execution risk in first-in-human programs, and continued non-cash charges/tax expense swings can influence reported results .
• Portfolio strategy: expect continued active management (prioritizations/partnerships) to align capital with highest-impact programs, consistent with ZW251 decision and commentary on future collaborations .

Citations:
Press release and 8-K for Q4 2024 financials, pipeline and approval .
Q4 2024 earnings call transcript remarks and Q&A .
Additional press releases (Q4 context and milestone) .
Prior quarters for trend analysis: Q3 2024 8-K and call ; Q2 2024 8-K and call .