ASCO’s Breakthrough Data Delivered: Ivonescimab Achieves OS Milestone, Varegacestat Establishes Best-in-Class Status, TUB-040 Shows Differentiated Potential

Overview

This report offers Goldman Sachs’ in-depth analysis of the core clinical data presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. It focuses on five covered companies—Summit Therapeutics (SMMT), Immunome (IMNM), Gilead (GILD), Incyte (INCY), and ArriVent Biopharma (AVBP)—systematically reviewing their latest Phase III and Phase II results in key areas such as lung cancer, rare tumors, ovarian cancer, lymphoma, and EGFR-mutant NSCLC, and updating investment views and valuations accordingly.

Core views

SMMT’s primary catalyst is ivonescimab, its partner Akeso’s PD-1xVEGF bispecific antibody. In the single-center Phase III HARMONi-6 trial, ivonescimab combined with chemotherapy achieved a median overall survival (OS) of 27.9 months in first-line squamous NSCLC, significantly outperforming the control arm of Tevimbra (a Keytruda-like agent) plus chemotherapy at 23.7 months (HR=0.66, p=0.0017). This marks the first PD-1/L1 combination therapy to demonstrate OS benefit in this indication, far exceeding the market’s expected HR<0.72 threshold. The result not only validates the earlier PFS advantage (11.1 vs 6.9 months) but also strongly supports SMMT’s ongoing global Phase III HARMONi-3 study (versus Keytruda). Additionally, SMMT’s Phase II data in metastatic colorectal cancer (mCRC) show that the 20 mg/kg dose group achieved a 9-month progression-free survival (PFS) rate of 76.1%, with superior efficacy and durability compared to the 10 mg/kg cohort, bolstering its global Phase III HARMONi-GI3 trial. IMNM’s varegacestat demonstrated comprehensive superiority in the Phase III RINGSIDE study for desmoid tumors: median PFS was not reached (NE), with 1-year/2-year PFS rates of 94.2%/88.9%, significantly higher than Ogsivevo’s 85%/76%. It also showed statistically significant improvements in key patient-reported outcomes (PROs) such as pain relief (WPI difference of -2.42), and had a lower incidence of ovarian toxicity (55.6%) compared to Ogsivevo, along with the added convenience of once-daily dosing. These data collectively establish its “best-in-class” status, paving the way for its 2026 NDA submission and subsequent commercialization. GILD’s TUB-040 performed exceptionally well in platinum-resistant ovarian cancer (PROC), achieving an objective response rate (cORR) of 61%, a disease control rate (DCR) of 96%, and a median PFS of 11 months—far above historical norms (~5 months). Its standout feature is its safety profile: no interstitial lung disease (ILD), ocular toxicity, or peripheral neuropathy—common “class effects” of ADC drugs—suggesting a wider therapeutic window and stronger potential for combination therapies. INCY’s tafasitamab combination regimen (Tafa-Len-R-CHOP) significantly prolonged PFS in first-line treatment of high-risk DLBCL (HR=0.75), increasing the 2-year PFS rate by 8.2 percentage points, and proving effective across both ABC-like and GCB-like subtypes. While slightly less safe than standard R-CHOP, it did not compromise the dosing intensity of the R-CHOP backbone and has been published in full in The Lancet. AVBP’s firmonertinib benefited from cross-validation by external data: Dizal’s sunvozertinib achieved a median PFS of 10.3 months in EGFR exon20 ins NSCLC, setting a reasonable benchmark for firmonertinib; JNJ’s Rybrevant combination demonstrated approximately 41 months of mature OS in atypical EGFR mutations, further validating the long-term commercial viability of this target and boosting confidence in firmonertinib’s development for more refractory PACC mutations.

Analysis framework

Goldman Sachs employs a three-dimensional analytical framework: clinical data-driven assessment, competitive landscape mapping, and commercialization potential evaluation. First, it rigorously benchmarks clinical endpoints (OS, PFS, ORR) against predefined thresholds (e.g., HR<0.72) to determine whether the data meet the milestone of being “statistically significant and clinically meaningful.” Second, it situates new data within the framework of standard-of-care (SoC) and major competitors (e.g., Ogsivevo, Pola-R-CHP, Datroway), using head-to-head or cross-trial comparisons to assess relative advantages in efficacy/safety/dosing. Finally, it integrates regulatory progress (NDA submissions), market opportunity (peak sales forecasts), and risk factors (clinical, regulatory, competitive) to arrive at a comprehensive value judgment and valuation modeling.

Methodology notes

• industry/sector analysis frameworkprice-volume decomposition

  separately evaluating clinical efficacy metrics (e.g., ORR, PFS, OS) and safety metrics (e.g., TRAE incidence, Grade ≥3 events) to comprehensively measure drug value

  When assessing TUB-040, the report highlights both its high ORR of 61% and its ‘differentiated safety’—lacking typical toxicities like ILD—indicating that the firm believes efficacy and safety must be considered independently, neither can be overlooked.

• industry/sector analysis frameworkcompetition and strategy framework

  moat/competitive advantage

  The report repeatedly emphasizes varegacestat’s ‘once-daily dosing,’ ‘superior ovarian safety profile,’ and ‘deeper responses,’ building its competitive barriers relative to Ogsivevo across three dimensions: dosing convenience, addressing key safety gaps, and depth of efficacy.

• company fundamentals and financial frameworkFree cash flow analysis

  DCF discounted cash flow valuation

  All targets are priced using the DCF model (e.g., SMMT at 85% risk-adjusted DCF plus 15% M&A value), indicating that the firm views the predictability of a company’s future cash flows and the discount rate as central to valuation, with particular attention to the pace of revenue realization driven by clinical success.

Asset mapping & comparison

Structured mapping from thesis to named assets (strengths, weaknesses, peers, risks).

• SUMMIT THERAPEUTICS INC (SMMT.US)

  holds global rights to the core asset, ivonescimab; Akeso’s HARMONi-6 OS data directly translate into SMMT’s clinical and commercial value

  Strengths

  owns exclusive rights to ivonescimab worldwide (except Greater China); the design of the global Phase III HARMONi-3 study is mature, with a clear readout timeline (H2 2026)

  Weaknesses

  All clinical data come from its Chinese partner, Akeso, posing risks of extrapolating data between Chinese and U.S. populations; uncertainties remain regarding U.S. FDA approval pathways and regulatory requirements

  Comparison

  Compared to other PD-1/L1xVEGF bispecifics (e.g., PF-4404), ivonescimab has already achieved positive OS results in NSCLC, leading by one clinical cycle

  Risks

  Akeso’s Chinese data may not replicate in SMMT’s global studies; changes in U.S.–China regulatory policies could impact collaboration and supply chains.

• Immunome Inc. (IMNM.US)

  is the global developer and applicant for varegacestat; ASCO data serve as the cornerstone for its上市申请 and commercialization

  Strengths

  varegacestat has built multi-dimensional advantages in efficacy, safety, and dosing convenience; the NDA has been submitted, with European MAA planned for completion within the year

  Weaknesses

  The desmoid tumor market is small, relying on high‑pricing strategies and精准诊断推广; there are currently no head‑to‑head studies directly proving superiority over Ogsivevo

  Comparison

  Compared to Ogsivevo, varegacestat outperforms in PFS, pain relief, and ovarian toxicity, but both belong to the GSI class with similar mechanisms—its differentiation lies more in clinical表现 than underlying principles

  Risks

  Regulatory bodies may not fully recognize cross‑trial comparative data; post‑上市医生教育 and patient accessibility pose challenges.

• Gilead Sciences Inc. (GILD.US)

  is the global developer of TUB-040; ASCO data represent a critical stepping stone toward registration-stage clinical trials

  Strengths

  TUB-040 exhibits an exceptional safety profile, avoiding major risks associated with ADC drugs; physician feedback has been highly positive, leaving room for后续组合疗法

  Weaknesses

  Still in Phase I/IIa, with no OS data yet released; in the fiercely competitive ovarian cancer arena, it must vie for市场份额 with approved PARPi, ADC, and other products

  Comparison

  Compared to同类NaPi2b-targeting ADCs, TUB-040 leads in ORR (61%) and safety (no ILD), but lacks direct head-to-head data with competing products

  Risks

  Dose optimization remains incomplete; there is a possibility of delays in launching registration-stage studies (FY27).

Key data

• HARMONi-6 OS (ivonescimab vs Tevimbra)27.9 months vs 23.7 monthsHR=0.66, p=0.0017; the first instance of surpassing PD-1 plus chemotherapy as standard-of-care in first-line squamous NSCLC.
• RINGSIDE PFS (varegacestat vs placebo)HR=0.16p<0.0001; 1-year/2-year PFS rates of 94.2%/88.9%, significantly better than Ogsivevo’s 85%/76%.
• TUB-040 cORR (PROC)61%includes 2 complete responses, DCR at 96%, median PFS at 11 months (vs historical 5 months).
• frontMIND PFS (Tafa-Len-R-CHOP vs R-CHOP)HR=0.75p=0.0194; 2-year PFS at 71.1% vs 62.9%, a difference of 8.2 percentage points.
• WU-KONG28 mPFS (sunvozertinib vs chemotherapy)10.3 months vs 7.5 monthsprovides a key efficacy anchor and safety reference for AVBP’s firmonertinib.

Impact & implications

These data have the following implications for the relevant companies: SMMT’s ivonescimab has received decisive validation for its global development path, significantly amplifying its potential in two major high-incidence cancers—NSCLC and mCRC; IMNM’s varegacestat, with its superior efficacy-safety balance and convenient dosing, is poised to quickly establish leadership in the niche but underserved desmoid tumor market; GILD’s TUB-040, if it maintains its current safety edge, could stand out in second-line ovarian cancer and lay the groundwork for expansion into first-line or combination therapies; INCY’s tafasitamab combination offers high-risk DLBCL patients a new, more universal treatment option, though it faces fierce competition from established regimens like Pola-R-CHOP; AVBP’s firmonertinib, bolstered by continuous positive external validation, sees its clinical development risks substantially reduced and its commercial prospects become clearer.

Risks

• SMMT: Clinical data generated by its Chinese partner, Akeso, may not replicate in SMMT-led global studies; regulatory and trade policy risks between the U.S. and Chinese biotech sectors; the possibility of failure in Phase III trials of ivonescimab in other cancers (e.g., mCRC).
• IMNM: Expansion of varegacestat into indications beyond desmoid tumors may fall short of expectations; insufficient commercial execution could result in sales below the projected peak of $1.6 billion.
• GILD: TUB-040 may fail to reproduce its excellent Phase I/IIa results in registration-stage trials; intensifying competition in the ovarian cancer market could increase pricing pressure.
• INCY: The tafasitamab combination may not achieve the PFS gains observed in Phase III trials in real-world settings; established competitors like Pola-R-CHOP maintain strong market share, slowing the penetration of the new therapy.
• AVBP: Firmonertinib may not meet key endpoints in the pivotal Phase III Furvent study; the EGFR exon20 ins space has seen the emergence of新一代更优势的抑制剂.

What to watch

• SMMT: Final PFS and interim OS data from the HARMONi-3 study, to be released in late 2026.
• IMNM: Progress of varegacestat’s review by the U.S. FDA and the timing of its NDA approval.
• GILD: Results of TUB-040’s dose optimization and the specific launch schedule for its registration-stage trials.
• INCY: Regulatory filing progress of the tafasitamab combination regimen and real-world comparison data with Pola-R-CHOP.
• AVBP: Topline data readout from the pivotal Phase III Furvent study of firmonertinib.