Zymeworks (ZYME) Soars on Positive Phase 3 Ziihera Data in Gastric Cancer – What Today’s Breakthrough Means for the Stock and Patients

Zymeworks Inc. (Nasdaq: ZYME) announced positive topline Phase 3 results from the HERIZON‑GEA‑01 trial of Ziihera® (zanidatamab‑hrii) in first‑line HER2‑positive gastroesophageal adenocarcinoma (GEA). ^[1]
Both Ziihera + chemotherapy and Ziihera + Tevimbra® (tislelizumab) + chemotherapy beat the current standard regimen of trastuzumab + chemotherapy on progression‑free survival (PFS), with the triple‑combination also showing a statistically significant overall survival (OS) benefit. ^[2]
Development partner Jazz Pharmaceuticals plans to file a supplemental Biologics License Application (sBLA) in 1H 2026, positioning Ziihera for potential approval as a new first‑line standard of care in HER2‑positive GEA. ^[3]
Pre‑market commentary this morning showed ZYME trading 30–50% higher on the news, although real‑time prices may fluctuate as regular trading progresses. ^[4]
The win comes shortly after Q3 2025 results, where Zymeworks reported 73% year‑over‑year revenue growth to $27.6M, strong cash of about $299M (runway into 2H 2027), but continued net losses. ^[5]

What Zymeworks Announced Today

Before the U.S. market open on November 17, 2025, Vancouver‑based Zymeworks Inc. (ZYME) released topline Phase 3 data from its pivotal HERIZON‑GEA‑01 study, evaluating Ziihera (zanidatamab‑hrii) in first‑line treatment of HER2‑positive locally advanced or metastatic gastroesophageal adenocarcinoma, a group that includes cancers of the stomach, gastroesophageal junction, and esophagus. ^[6]

The trial compared three regimens:

Control arm: Trastuzumab (Herceptin®) + chemotherapy (the current global standard in HER2+ GEA) ^[7]
Ziihera + chemotherapy
Ziihera + Tevimbra (tislelizumab) + chemotherapy

According to Zymeworks and its partners Jazz Pharmaceuticals and BeOne Medicines, HERIZON‑GEA‑01 delivered several key findings: ^[8]

Primary endpoint met: Both Ziihera‑based arms showed highly statistically significant and clinically meaningful improvements in PFS versus trastuzumab + chemotherapy.
Overall survival benefit:
- Ziihera + Tevimbra + chemo achieved a statistically significant and clinically meaningful OS improvement vs. control.
- Ziihera + chemo showed a clinically meaningful OS benefit with a strong trend toward statistical significance at this first interim OS analysis; the trial will continue, with another OS look expected in mid‑2026.
Consistent benefit across PD‑L1 subgroups: The three‑drug regimen improved PFS and OS in both PD‑L1‑positive and PD‑L1‑negative patients, suggesting broad applicability.
Stronger responses: Both Ziihera‑based regimens improved objective response rate (ORR) and duration of response (DoR) vs. trastuzumab + chemo, supporting the primary efficacy findings.
Manageable safety profile: Safety was consistent with the known profiles of Ziihera, Tevimbra and chemotherapy; no new safety signals were observed, supporting a favorable overall benefit‑risk profile.

On the back of these data, Jazz plans to: ^[9]

Present full results at a major medical meeting in Q1 2026.
Submit an sBLA in the first half of 2026 to support Ziihera’s approval as first‑line therapy in HER2+ GEA, with or without Tevimbra.
Seek rapid adoption into NCCN Guidelines® for gastric and gastroesophageal cancers.

For Zymeworks, which originally discovered Ziihera using its Azymetric™ bispecific antibody platform, the company is eligible for additional regulatory and commercial milestones and tiered royalties on net sales through its licensing deals with Jazz and BeOne. ^[10]

Why HERIZON‑GEA‑01 Could Be a Game Changer

A high‑need patient population

HER2‑positive gastroesophageal adenocarcinoma is aggressive and often diagnosed at an advanced stage. While trastuzumab + chemotherapy improved survival when it became the standard of care, outcomes remain poor and resistance frequently develops. ^[11]

Prior Phase 2 data from Zymeworks already hinted that Ziihera combined with chemotherapy could deliver deeper and more durable responses than historical benchmarks, prompting the global Phase 3 HERIZON‑GEA‑01 program. ^[12]

Ziihera: not just another HER2 antibody

Ziihera (zanidatamab‑hrii) is a bispecific HER2‑targeted antibody that binds two distinct sites on the HER2 receptor, designed to more effectively cluster and downregulate HER2‑expressing tumor cells compared to traditional monoclonal antibodies. ^[13]

The drug is already approved in the U.S., Europe and China for previously treated HER2‑positive biliary tract cancer, where it became the first dual HER2‑targeted bispecific antibody cleared for that indication. ^[14]

For GEA, HERIZON‑GEA‑01 is critical because it:

Directly compares Ziihera‑based regimens against the current standard of trastuzumab + chemo. ^[15]
Shows both PFS and OS advantages, especially when combined with the PD‑1 inhibitor Tevimbra (tislelizumab), which is already approved in several gastric and esophageal cancer settings. ^[16]
Demonstrates benefit regardless of PD‑L1 status, simplifying biomarker‑driven treatment decisions in the clinic.

Zymeworks explicitly states that the results support Ziihera as the “HER2‑targeted agent‑of‑choice” and a “new standard of care” in first‑line HER2‑positive GEA—ambitious language, but one that’s now backed by a successful Phase 3 program. ^[17]

How the Market Is Reacting to ZYME Stock

News of a successful oncology Phase 3 trial is exactly the kind of catalyst biotech investors watch for—and Zymeworks is seeing that play out today:

Pre‑market trading coverage from several outlets reported sharp gains:
- GuruFocus cited about a 32% surge in premarket trading after the data dropped. ^[18]
- Benzinga listed Zymeworks among premarket healthcare leaders, with shares up more than 40% at around $25.97. ^[19]
- European coverage highlighted intraday gains above 50% among top movers. ^[20]
According to the latest Nasdaq quote available via market data tools, Zymeworks BC Inc (ZYME) is recently trading around $18.52, essentially flat versus the prior close (+0.2%).

The gap between pre‑market indications and official last‑trade data likely reflects low‑liquidity early quotes and the fact that regular U.S. trading may still be ramping up. As volume builds, the stock could settle at a level more clearly reflecting the perceived value of HERIZON‑GEA‑01.

Either way, the tone of market coverage is distinctly positive: Barron’s, MarketWatch, Morningstar and others all emphasize strong trial efficacy and rising shares for both Zymeworks and partner Jazz Pharmaceuticals following the announcement. ^[21]

Financial Backdrop: Q3 2025 Shows Progress, But Zymeworks Remains Loss‑Making

Today’s trial success comes just 11 days after Zymeworks reported Q3 2025 earnings and a broader corporate update.

From analyst and media summaries of the quarter: ^[22]

Revenue:
- $27.6 million in Q3 2025, up from $16 million a year earlier—73% year‑over‑year growth.
- The increase was driven largely by a $25 million development milestone from a collaboration with Johnson & Johnson.
Profitability:
- Net loss improved to about $19.6 million (vs. ~$29.9 million in Q3 2024) but remains substantial.
- Zymeworks also noted high operating expenses of roughly $49.7 million, only modestly reduced year‑over‑year.
Cash and runway:
- Cash, cash equivalents and marketable securities totaled about $299.4 million as of September 30, 2025.
- Management and analysts estimate that this funds operations into the second half of 2027, assuming current plans.
Capital allocation:
- Zymeworks completed around $22.7 million of share repurchases, signaling management’s confidence in the company’s long‑term outlook.

Consensus models compiled by Simply Wall St. now project 2026 revenue of roughly $152.8 million, up about 14% vs. the last 12 months, with per‑share losses narrowing but not yet turning profitable (forecast EPS around –$0.81). ^[23]

The HERIZON‑GEA‑01 win could materially alter those forecasts depending on:

The speed and scope of regulatory approvals in the U.S., Europe, China and beyond.
The level of commercial uptake in first‑line GEA versus entrenched regimens from big pharma competitors.
The magnitude and timing of milestone and royalty payments from Jazz and BeOne, which flow directly to Zymeworks’ top line with comparatively modest incremental costs. ^[24]

Pipeline and Strategy Beyond Ziihera

Zymeworks is positioning itself as a platform‑driven oncology company, not a one‑drug story.

Recent corporate updates highlight: ^[25]

Azymetric™ and ADC platforms:
- Ziihera is the flagship product of the Azymetric bispecific antibody platform.
- The company is also building a suite of antibody‑drug conjugates (ADCs) for solid tumors.
ZW191 (FRα‑targeted ADC):
- Early Phase 1 data have shown meaningful tumor reductions with a favorable safety profile, encouraging further development.
ZW251:
- A next‑generation ADC program; Phase 1 studies are actively recruiting, with an investigational new drug (IND) strategy extending into multiple solid tumor settings. ^[26]
Portfolio pruning:
- In September 2025, Zymeworks discontinued development of ZW171, a mesothelin‑directed T‑cell engager, after it failed to meet internal thresholds—an example of the company reallocating resources toward programs with stronger risk‑reward profiles. ^[27]
Partnership ecosystem:
- In addition to Jazz and BeOne, Zymeworks maintains collaborations with GSK and others, including a $14 million milestone payment announced in February 2025 related to its partnered pipeline. ^[28]

This portfolio approach means that value from Ziihera (if fully realized) could fund and de‑risk development of a broader oncology franchise, while partnerships share clinical and commercial risk.

Key Risks and Competitive Landscape

Even on a day of clear good news, investors—and journalists writing for Google News or Discover—should keep the risk side of the ledger in view:

Regulatory uncertainty
- The HERIZON‑GEA‑01 data are topline only. Regulators will scrutinize the full dataset, including specific hazard ratios, subgroup details, and safety in longer follow‑up.
- The sBLA filing is expected in 1H 2026; approval is not guaranteed and timelines can shift. ^[29]
Competition in HER2‑positive gastric cancer
- Ziihera will compete with established HER2‑targeted regimens built around trastuzumab and newer agents (including antibody‑drug conjugates) being developed by major oncology players. ^[30]
- Pricing, guideline positioning, and payor coverage will heavily influence market share.
Execution by partners
- Zymeworks relies on Jazz and BeOne for late‑stage development, regulatory interactions and commercialization of Ziihera in GEA and other HER2‑positive tumors. Any strategic shift or misstep by partners can ripple back to Zymeworks. ^[31]
Ongoing cash burn and pipeline risk
- Despite a solid cash runway, Zymeworks remains loss‑making, with high R&D and operating costs. ^[32]
- Other pipeline assets may fail, be delayed, or require costly larger studies.
Valuation and volatility
- Small‑ and mid‑cap biotech stocks commonly experience sharp moves around key data events. Today’s rally may or may not be sustainable once analysts fully model the long‑term revenue and royalty impact of Ziihera in first‑line GEA.

What to Watch Next

For readers tracking Zymeworks (ZYME) over the coming months, several milestones stand out:

Q1 2026 – Detailed HERIZON‑GEA‑01 data presentation at a major medical oncology conference. ^[33]
1H 2026 – Planned sBLA submission by Jazz for Ziihera (with or without Tevimbra) in first‑line HER2‑positive GEA in the U.S. ^[34]
Mid‑2026 – Next overall survival interim analysis for the Ziihera + chemo arm. ^[35]
Ongoing – Updates on ZW191 and ZW251 early‑stage trials, further ADC pipeline additions, and any new business development deals. ^[36]

Bottom Line

On November 17, 2025, Zymeworks delivered the kind of news that can reshape a biotech’s long‑term narrative:

A successful Phase 3 trial in a large, high‑need cancer indication.
A credible path to label expansion for an already approved targeted therapy.
The prospect of meaningful royalty and milestone streams that could complement its growing ADC and multispecific antibody pipeline.

While important questions remain about competition, commercialization, and valuation, HERIZON‑GEA‑01 firmly moves Ziihera closer to becoming a new standard of care in HER2‑positive gastric and gastroesophageal cancers—and puts Zymeworks squarely back on the radar of oncology watchers and growth‑oriented biotech investors.

Can we defeat cancer? (w/ Dr. Ali Tehrani, CEO of Zymeworks)