ASCO 2025 / Time to Reclaim Boldness in Oncology

ASCO 2025 Reveals a System Under Strategic Stress

By Jenny Knauss, PhD and Nikil Kumar / June 2025

Executive Summary

While ASCO 2025 may not have delivered the headline-grabbing breakthroughs of past years, it provided a critical pause for reflection. The field is maturing—but with that maturity comes a challenge: how do we avoid the comfort of incrementalism and reignite the ambition that has defined oncology for the past two decades?

At Kx Advisors, we see this moment not as a slowdown, but as a strategic opportunity. The future will belong to companies that balance smart, near-term execution with bold bets on novel targets, innovative platforms, and underexplored tumor types. We’re partnering with clients to build portfolios with purpose, commercialize with precision, and ensure that the next decade of oncology isn’t defined by more of the same—but by more of what’s possible.

KOLs were unified in their sentiment: ASCO 2025 showcased a field that is entering a new phase of evolution. Rather than disruptive paradigm shifts, we saw strategic refinement—confirmatory trials, long-term durability updates, and smart extensions of proven mechanisms. While headline-grabbing breakthroughs were fewer, this year’s meeting offered valuable signals of how the oncology community is becoming more rigorous, more disciplined, and more deliberate in pursuit of meaningful patient impact.

The question remains however — “is this a sustainable strategy that will advance oncology and are we doing enough today to seed breakthrough innovation that will deliver transformative outcomes tomorrow?”

ASCO 2025 saw

• Incremental updates to established PD-1 and HER2 regimens
• Late-to-market assets searching for slivers of differentiation in crowded spaces
• Overuse of the “line extension” playbook to justify marginal programs
• A clear absence of novel targets, platforms, or first-in-class mechanisms

What’s Driving This Slowdown?

1. Over-dependence on De-risked, “Fast Follower” Strategies
   Biopharma pipelines are heavily skewed toward known pathways and well-characterized targets. The pursuit of regulatory clarity and commercial precedent has created a copycat cycle
   “We’ve mastered PD-1. But we’ve also exhausted its room to differentiate.” —KOL, Thoracic Oncology, ASCO panel
2. Misplaced Bet on Speed as Strategy
   Speed to market is not inherently wrong—but when it becomes the endgame, rather than a means to patient impact, it yields underwhelming innovation
3. Short-Term Portfolio Thinking in an Era of Scientific Complexity and Capital Constraints
   Federal and institutional funding for early-stage oncology research is contracting at the same time that cost of capital is rising. Instead of stepping in to lead, many biopharma players are retreating into near-term revenue plays

1. Market Saturation Without Differentiation
   Me-too products in mature tumor types dilute pricing power, cannibalize share, and struggle to stratify meaningfully distinct patient subgroups making trial recruitment and clinical advancement a challenge. Even real-world evidence can’t rescue undifferentiated assets
2. Unmet Need Continues to Go Unmet
   Tumors with complex biology, rare indications, or weak biomarkers are systematically overlooked—despite potentially higher value creation for the first movers
3. Structural Decline in Target Discovery and Modality Advancement
   The lack of investment (both public funding and private sector backing) in early biology and enabling tech (e.g., novel targets, synthetic lethality, AI-driven target ID, or functional genomics) suggests a long-term pipeline drought is coming

1. Reframing Portfolio Strategy Around Intentional Risk
   We build portfolio strategies that incorporate risk—and reward—intelligently. We help clients balance de-risked assets with bold plays in novel mechanisms, therapeutic modalities, and uncharted tumor types.
   — Instead of stacking PD-1 combos in NSCLC, one client reweighted their early pipeline toward myeloid-targeted IO in AML and saw 3 new academic co-dev deals in 12 months
2. Bringing Rare Disease Commercialization Rigor to Early Oncology Launches
   We apply rare disease-style precision to launch planning for oncology: tightly segmented stakeholder maps, value narrative development pre-Ph2, and early access strategy integration
   — For a bispecific in a niche head & neck subtype, our client moved from Phase 2 to global launch readiness with fewer than 30 FTEs and 18 months of prep—hitting 90% of projected revenue in Year 1
3. Rebalancing Opportunity Assessment Toward Scalable Commercial Value
   We go beyond technical feasibility. Our BD support and organic opportunity assessments quantify long-term potential across access, KOL adoption, diagnostic burden, and pricing power—not just trial complexity and heavily weighted probability of trial and regulatory success (PTRS) scores
   — One biotech walked away from a “low-hanging fruit” ADC and instead acquired a next-gen mRNA neoantigen platform—with our help reframing the case for long-term portfolio leverage through deep customer insights that more accurately predicted adoption potential based on real-world experience with oncologists

Not every company is playing it safe. A few are charting a path forward that reflects strategic courage, scientific vision, and commercial pragmatism.

BioNTech

• PD-L1 x VEGF-A bispecific (BNT327) which is a shrewd and differentiated response to PD-1 market saturation (and recent disappointments) with a mechanistically rational and immunologically relevant combination focused on the tumor and tumor microenvironment
• LCM driven by unmet need, not ease of execution: choosing rare and resistant tumor types to differentiate and add long-term franchise value
• A diversified combination and portfolio ambition to advance novel targets and platforms including ADCs, mRNA cancer vaccines that will require new thinking and bold clinical endpoints

Arcus Biosciences

• A bold and scientifically grounded commitment to immunometabolism, continuing development in the adenosine axis (CD73, A2aR) and expanding into HIF-2 and TIGIT combinations despite prior market hesitation
• An intentional clinical strategy focused on rational, mechanism-based combinations with PD-1, CTLA-4, and chemo to unlock efficacy in cold or resistant tumors
• A long-horizon partnership with Gilead that de-risks pipeline investment while enabling Arcus to pursue platform depth across novel IO targets, without pressure to rush unproven programs to market

Bicycle Therapeutics

• Pioneering a completely novel modality—bicyclic peptides—that offer antibody-like specificity with small molecule-like pharmacokinetics, enabling better tumor penetration and faster clearance
• A differentiated development focus on hard-to-treat solid tumors (e.g., bladder, lung) with first-in-class programs like BT8009 (Nectin-4 BTC) and BT7480 (CD137 x Nectin-4 TICA) designed to overcome known limitations of ADCs and TCEs
• A scalable and modular platform approach with strategic expansion into radiopharmaceuticals and toxin-conjugated “bicycles,” plus smart partnerships (e.g., Ionis, Bayer) to extend reach and accelerate innovation

ASCO 2025 showed us that the innovation engine isn’t broken—but it is misdirected. The question now isn’t just what the next target is, but whether we’ve created the conditions for bold science to thrive.