Summit Therapeutics’ (SMMT) latest tweak to its clinical playbook has turned what was already one of biotech’s higher‑stakes stories into something closer to appointment viewing for Wall Street.
A Phase 3 Trial Adds a Plot Twist
Summit now plans an interim progression‑free survival (PFS) analysis in its global Phase 3 HARMONi‑3 trial, which pits ivonescimab plus chemotherapy against pembrolizumab plus chemotherapy in first‑line squamous non‑small cell lung cancer. Previously, investors were told to wait for final PFS and interim overall survival (OS) data in the back half of 2026, with no interim look on the calendar.
The company’s stated rationale is to accelerate dialogue with the US Food and Drug Administration and potentially speed access to ivonescimab for patients. Skeptics may note that “accelerate dialogue” is biotech shorthand that can cover everything from genuine regulatory urgency to a desire to reframe the narrative, but in this case the statistics quietly do some of the talking.
Why an Interim Look Matters
Ivonescimab, a PD‑1 x VEGF bispecific antibody licensed from Akeso, has already delivered statistically significant PFS wins in Phase 3 trials such as HARMONi‑2 and HARMONi‑6, where it beat leading PD‑1 competitors in non‑small cell lung cancer. In HARMONi‑6, for example, ivonescimab plus chemotherapy reduced the risk of progression by roughly 40% versus tislelizumab plus chemotherapy in first‑line squamous NSCLC, establishing the molecule as a serious head‑to‑head contender.
By pulling PFS into its own interim analysis in HARMONi‑3 and decoupling it from OS, Summit is effectively creating a high‑probability “win” event: a clean read on a primary endpoint where ivonescimab’s track record is strongest and where prior Akeso data already suggest a favorable profile versus the PD‑1 class. If positive, HARMONi‑3 could become the first global trial to show a PFS advantage over pembrolizumab in a front‑line lung setting, a data point likely to resonate with both regulators and payers.
Short Sellers, Meet a Binary Catalyst
Despite the drumbeat of positive external data, a material contingent of investors has been positioned on the other side of the trade: as of recent Nasdaq data, roughly 36% of Summit’s float was sold short. The bear case has been straightforward and, until now, convenient: PFS may look good, but the real question is OS, and that will take time.
The new interim design does not resolve the OS debate; ivonescimab will still need to deliver both robust PFS and meaningful OS benefit to secure global standard‑of‑care status. What it does do is change the cadence of potential pain for those betting against the stock, inserting a high‑visibility data event earlier in the calendar where the probabilities are no longer comfortably symmetric. In a market that has grown accustomed to fading biotech rallies, HARMONi‑3’s interim look could function more like a scheduled margin‑call on pessimism.
Building a Franchise, Not Just a Single Trial
Beyond HARMONi‑3, Summit and Akeso are quietly assembling something larger than a one‑trial story. The Phase 3 HARMONi program in EGFR‑mutated NSCLC has already delivered a favorable overall survival trend, with ivonescimab plus chemotherapy showing a median OS of 16.8 months versus 14.0 months for placebo plus chemotherapy in Western patients, and additional follow‑up is underway. Akeso’s HARMONi‑2 trial has reported a 49% reduction in risk of progression versus pembrolizumab in PD‑L1–positive NSCLC, while HARMONi‑6 has set a new bar for head‑to‑head PFS versus a PD‑1 inhibitor plus chemotherapy in squamous disease.
Summit’s own pipeline layering continues with ILLUMINE, a Phase 3 head and neck cancer study run with EU cooperative group GORTEC, and with combination efforts alongside Revolution Medicines’ RAS inhibitors and GSK’s B7‑H3 antibody–drug conjugate. Together, these trials test whether ivonescimab’s dual‑targeting architecture and tumor‑directed binding can translate into a multi‑tumor, multi‑modality franchise rather than a single‑indication curiosity.
Fundamentals Catch Up to the Narrative
For a company that reported zero revenue in 2024 and 2025 and a net loss of $219 million in the fourth quarter of 2025 alone, Summit’s balance sheet looks more robust than its income statement would suggest. The company ended 2025 with approximately $713 million in cash and investments, a runway Cantor Fitzgerald expects to extend into 2027 even as R&D spending ramps to support multiple late‑stage trials.
Analysts at Cantor Fitzgerald carry an Overweight rating on Summit, underpinned by a discounted cash flow valuation that points to material upside if ivonescimab’s lung program matures as planned. Their modeling assumes ivonescimab‑driven revenue stepping up meaningfully from 2028 onward, with operating margins expanding as the company transitions from a development‑stage biotech to a commercial oncology platform anchored in lung cancer but with options in additional solid tumors. In other words, the Street’s debate is no longer about whether there is a business here—it is about how big, and how soon.
The Sources
[1] Small-Change-in-Strategy…-Big-Change-in-Storyline-2.pdf https://ppl-ai-file-upload.s3.amazonaws.com/web/direct-files/attachments/24996935/844e298c-fc5f-484f-b3db-10c9a8cbf38b/Small-Change-in-Strategy…-Big-Change-in-Storyline-2.pdf
[2] Cantor Fitzgerald maintains Overweight on Summit Therapeutics https://www.investing.com/news/analyst-ratings/cantor-fitzgerald-maintains-overweight-on-summit-therapeutics-93CH-3999216
[3] U.S. Patients & Caregivers – HARMONi-3 Clinical Trial https://smmttx.com/patients-caregivers/harmoni-3-clinical-trial/default.aspx
[4] HARMONi-3 Clinical Trial – Summit Therapeutics Inc. https://www.smmttx.com/clinical-trials/harmoni-3-clinical-trial/
[5] Akeso Announces The Publication of Its Phase III Clinical Trial … https://www.prnewswire.com/news-releases/akeso-announces-the-publication-of-its-phase-iii-clinical-trial-results-for-ivonescimab-in-head-to-head-comparison-with-pembrolizumab-in-the-lancet-302395382.html
[6] Summit Therapeutics Announces U.S. FDA Acceptance of Biologics … https://smmttx.com/news/press-releases/news-details/2026/Summit-Therapeutics-Announces-U-S–FDA-Acceptance-of-Biologics-License-Application-BLA-Seeking-Approval-for-Ivonescimab-in-Combination-with-Chemotherapy-in-Treatment-of-Patients-with-EGFRm-NSCLC-Post-TKI-Therapy/default.aspx
[7] HARMONi-6, Featuring Ivonescimab Combined with Chemotherapy … https://www.biospace.com/press-releases/harmoni-6-featuring-ivonescimab-combined-with-chemotherapy-vs-tislelizumab-plus-chemotherapy-in-1l-treatment-of-patients-with-squamous-nsclc-in-china-to-be-showcased-in-presidential-symposium-at-esmo-2025
[8] Ivonescimab, a Dual-Targeting Bispecific Antibody, Improves … https://ascopost.com/issues/november-25-2025/ivonescimab-a-dual-targeting-bispecific-antibody-improves-progression-free-survival-in-squamous-nsclc/
[9] Summit Therapeutics’ Bispecific Antibody Shows Positive Survival … https://www.appliedclinicaltrialsonline.com/view/summit-therapeutics-bispecific-antibody-positive-survival-trend-non-small-cell-lung-cancer
[10] Cantor Fitzgerald maintains Overweight on Summit Therapeutics … https://www.investing.com/news/analyst-ratings/cantor-fitzgerald-maintains-overweight-on-summit-therapeutics-shares-93CH-3951787
[11] Cantor Fitzgerald Initiates Coverage of Summit Therapeutics (SMMT … https://www.nasdaq.com/articles/cantor-fitzgerald-initiates-coverage-summit-therapeutics-smmt-overweight-recommendation
[12] News Details – Summit Therapeutics https://smmttx.com/news/press-releases/news-details/2025/Longer-Term-Follow-Up-of-Western-Patients-Showed-Improving-Favorable-Trend-in-Overall-Survival-in-Global-Phase-III-HARMONi-Clinical-Trial-for-Ivonescimab-Plus-Chemotherapy-in-2L-EGFRm-NSCLC/default.aspx
[13] Summit Therapeutics Announces Expansion of Ivonescimab Global … https://smmttx.com/news/press-releases/news-details/2025/Summit-Therapeutics-Announces-Expansion-of-Ivonescimab-Global-Phase-III-Development-Program-with-HARMONi-GI3-Study-in-1L-Colorectal-Cancer/default.aspx
[14] NCT05899608 | Clinical Study of Ivonescimab for First-line … https://clinicaltrials.gov/study/NCT05899608
[15] Ivonescimab Overview – Summit Therapeutics https://smmttx.com/ivonescimab-smt112/ivonescimab-overview/default.aspx
[16] Ivonescimab Plus Chemotherapy Demonstrates a Statistically … https://www.smmttx.com/news/press-releases/news-details/2025/Ivonescimab-Plus-Chemotherapy-Demonstrates-a-Statistically-Significant-Benefit-in-Overall-Survival-with-a-Hazard-Ratio-of-0-74-in-2L-Treatment-of-Patients-with-EGFRm-NSCLC-in-HARMONi-A-Study-Conducted-by-Akeso-in-China/default.aspx
