Merck & Co. Inc. / Terns Pharmaceuticals, Inc.

Chronic Myeloid Leukemia (CML)

10K US cases/yr · $8.0B Global CML TKI therapeutics market (2025) · 15-25% Share of CML patients developing TKI resistance/intolerance (second-line+ market)

Disease Overview

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion oncoprotein, a constitutively active tyrosine kinase produced by the Philadelphia chromosome translocation t(9;22)(q34;q11). CML represents about 15% of all adult leukemias. Per the NCI SEER program, CML incidence is approximately 2.1 per 100,000 per year, age-adjusted; the American Cancer Society projects approximately 9,650 new CML diagnoses in the United States in 2026 (5,810 men, 3,840 women) with approximately 1,170 deaths. Median age at diagnosis is 66. The therapeutic revolution began with imatinib (Gleevec) in 2001, which converted CML from a fatal to a chronic, manageable disease. Second- and third-generation ATP-competitive TKIs (dasatinib, nilotinib, bosutinib, ponatinib) and the first-in-class allosteric STAMP inhibitor asciminib (Scemblix) have further improved response rates. Despite this, approximately 15-25% of patients develop TKI resistance or intolerance, often driven by the gatekeeper T315I mutation or cumulative off-target toxicity, making novel allosteric agents a commercially and clinically important segment. 10-year survival now exceeds 85% in TKI-responsive patients.

Competitive Landscape

CML therapeutics is a mature market anchored by BCR::ABL1 TKIs across three generations. Generic imatinib (Gleevec, Novartis, launched 2001) remains widely used first-line. Second-generation ATP-competitive TKIs include dasatinib (Sprycel, BMS/generic), nilotinib (Tasigna, Novartis), and bosutinib (Bosulif, Pfizer). Third-generation ponatinib (Iclusig, Takeda) covers T315I resistance but carries cardiovascular toxicity. The paradigm-shifting launch was asciminib (Scemblix, Novartis, 2021) - the first STAMP (Specifically Targeting ABL Myristoyl Pocket) allosteric inhibitor - which generated approximately $1.3B in 2025 global sales and won first-line label expansion based on the ASC4FIRST trial showing superior efficacy and tolerability vs. standard-of-care TKIs. TERN-701 competes as a next-generation oral allosteric BCR::ABL1 TKI and second STAMP inhibitor with once-daily dosing without food restriction, vs. Scemblix's twice-daily regimen with meal timing. Phase 1/2 CARDINAL data show major molecular responses in heavily pre-treated patients who progressed on asciminib. Emerging competitors include Ascentage's olverembatinib (GZD824, Phase 3 in T315I-resistant CML) and Sun Pharma's HQP1351.