Ivonescimab’s Robust Clinical Results Lead to Major BLA Filing Plans
Summit Therapeutics (NASDAQ: SMMT) is preparing a major step in its clinical ambitions: a Biologics License Application (BLA) submission in late 2025 for ivonescimab plus chemotherapy, based on compelling data from the global Phase III HARMONi trial in EGFR-mutated non-small cell lung cancer (NSCLC). This follows data showing ivonescimab combined with chemotherapy reduced the risk of disease progression or death by 48% compared to chemotherapy alone (hazard ratio 0.52; median progression-free survival of 6.8 vs. 4.4 months), with consistent benefit observed across regions.
HARMONi and HARMONi-6 Data Signal Strong Efficacy, Even Versus Modern Immunotherapies
In addition to the primary HARMONi study, results from Akeso’s HARMONi-6 trial in China reported a 40% reduction in risk of progression or death compared to PD-1 inhibitor tislelizumab plus chemotherapy in first-line squamous NSCLC, with median progression-free survival extending to 11.14 months for ivonescimab regimens versus 6.9 months for the comparator arm.
The overall response rates in the HARMONi trial were also higher for ivonescimab plus chemotherapy (45% vs. 34%), with duration of response nearly doubled (7.6 months vs. 4.2 months), further reinforcing the regimen’s potential to address unmet need in the NSCLC space, where few regimens have demonstrated overall survival benefits to date.
Ambitious Global Trial Expansion Targets Multiple Tumor Types
Summit’s R&D expansion is not stopping at NSCLC. With a newly launched global Phase III trial (HARMONi-GI3) for unresectable metastatic colorectal cancer (CRC), and multiple new Phase III studies on the horizon, Summit is executing on a broad development program. The company is collaborating with leading cancer centers, as well as evaluating combinations with novel RAS inhibitors in partnership with Revolution Medicines. These programs highlight an aggressive push to establish ivonescimab as a foundational asset in solid tumor oncology across multiple geographies and indications.
R&D Spend Surges Alongside Expanded Pipeline—Stock Compensation Heavily Impacts GAAP Losses
These scientific strides have come with substantial increases in spending. For the third quarter ended September 30, 2025, Summit reported:
| Metric | Q3 2025 | Q3 2024 | YTD 2025 | YTD 2024 |
|---|---|---|---|---|
| GAAP Operating Expenses | $234.2M | $58.4M | $869.5M | $160.4M |
| Non-GAAP Operating Expenses | $103.4M | $39.0M | $248.9M | $120.5M |
| GAAP Net Loss | $(231.8)M | $(56.3)M | $(860.4)M | $(160.1)M |
| Non-GAAP Net Loss | $(101.0)M | $(36.9)M | $(239.8)M | $(120.2)M |
| Cash & Short-Term Investments (Sept. 30, 2025) | $238.6M | $412.3M (Dec. 31, 2024) | ||
The large gap between GAAP and non-GAAP metrics reflects over $130 million in Q3 stock-based compensation charges, driven by changes in performance-based equity awards. The surge in non-GAAP expenses highlights the ongoing build-out of Summit’s infrastructure and R&D workforce in preparation for regulatory filings and commercial operations.
Safety Data Consistent Across Studies
Across multiple trials, ivonescimab plus chemotherapy maintained an acceptable safety profile. In HARMONi, 7.3% discontinued due to adverse events versus 5.0% on placebo; deaths from treatment-related events were comparable between groups. The rate of grade 3 or higher hemorrhagic events was low (0.9%). These results align with the manageable safety seen in HARMONi-6, where severe adverse event discontinuations and death rates were similar between arms, despite some increase in VEGF-related side effects as expected for the drug class.
Looking Forward: Key Milestones on the Horizon
- BLA submission for ivonescimab in EGFR-mutated NSCLC planned for Q4 2025
- Enrollment completion in global Phase III HARMONi-3 (squamous and non-squamous cohorts) expected through 2026
- Launch of multiple new Phase III trials—including HARMONi-GI3 in CRC and solid tumors with RAS mutations
Summit is setting the stage for ivonescimab to move toward regulatory approval in key western markets. Investors will want to monitor enrollment milestones and upcoming data releases, particularly regarding overall survival trends and safety in diverse populations. The company’s rapid increase in R&D investment, and expansion of the pipeline, marks Summit’s transformation into a late-stage biopharma—though sustained financial losses and dependency on clinical milestones remain important factors to watch.
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