TERN-701's Path to Becoming a Best-in-Class CML Therapy: Evaluating Clinical, Strategic, and Market Potential

The chronic myeloid leukemia (CML) treatment landscape is undergoing a quiet revolution, driven by the limitations of existing therapies and the urgent need for better options in a patient population that often faces resistance and intolerance to current treatments. At the forefront of this evolution is Terns Pharmaceuticals and its lead candidate, TERN-701, an oral, next-generation allosteric BCR-ABL inhibitor. With a 50% cumulative major molecular response (MMR) rate observed in heavily pre-treated patients after 12 weeks in the Phase 1 CARDINAL trial, TERN-701 is emerging as a compelling contender to redefine the standard of care [1]. This article evaluates the clinical, strategic, and market potential of TERN-701, assessing how Terns Pharmaceuticals is positioning itself to capture a significant share of a rapidly growing $12.07 billion CML market by 2030 [2].

Clinical Differentiation: A New Mechanism for a Challenging Disease

The cornerstone of TERN-701’s potential lies in its mechanism of action. Unlike traditional tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib, which bind to the active site of the BCR-ABL protein, TERN-701 targets the myristoyl pocket—an allosteric site. This distinction is critical. First- and second-generation TKIs, while transformative in CML management, face challenges with resistance mutations (e.g., T315I) and long-term toxicity [3]. Asciminib, the first allosteric inhibitor approved for CML, has shown promise but still struggles with resistance in some patients [4].

TERN-701’s preclinical and early clinical data suggest it overcomes these hurdles. In the CARDINAL trial, the drug achieved a 50% MMR rate in non-T315I mutation patients at 12 weeks, even in those who had failed multiple prior therapies, including asciminib [1]. Notably, 88% of patients with high baseline BCR-ABL transcript levels (>1%) saw reductions, a feat that underscores its potency in a difficult-to-treat cohort [5]. Safety data further bolster its case: no dose-limiting toxicities, no serious adverse events, and no dose reductions or discontinuations were reported across the 160–400 mg dose range [1]. This favorable profile contrasts with second-generation TKIs, which are associated with distinct hematologic toxicities (e.g., dasatinib’s anemia, nilotinib’s insulin resistance) [3].

Strategic Positioning: Capitalizing on Market Gaps

Terns Pharmaceuticals is not merely developing a drug—it is engineering a strategic repositioning in the CML space. The company’s decision to advance TERN-701 independently, without external partnerships, reflects confidence in its clinical profile and the unmet need it addresses. With $315.4 million in cash and equivalents as of June 2025, Terns has the financial runway to fund TERN-701 through pivotal trials and into commercialization [6]. This contrasts with its approach to metabolic disease assets like TERN-601 (a GLP-1 RA for obesity), where the company plans to seek partnerships beyond 2025 due to the high costs and competitive risks in that market [6].

The CML market itself is a fertile ground for disruption. While TKIs dominate 74.56% of revenue in 2024, their long-term use is often complicated by resistance and side effects [7]. Meanwhile, newer therapies like asciminib, though innovative, have yet to achieve universal adoption. TERN-701’s once-daily dosing, improved drug-drug interaction profile, and preclinical superiority against resistance mutations position it to fill this gap [1]. By targeting patients who have exhausted existing options, Terns is not only addressing a niche but also building a foundation for broader adoption as the drug progresses through trials.

Market Dynamics: A $12 Billion Opportunity

The CML market is projected to grow at a compound annual rate of 6.38%, reaching $12.07 billion by 2030 [2]. This growth is fueled by three factors: rising incidence of CML, advancements in treatment-free remission protocols, and the demand for therapies that improve long-term outcomes. TERN-701’s potential to deliver deep molecular responses and sustained remission aligns perfectly with these trends.

Moreover, Terns is capitalizing on the geographic and therapeutic diversification of the CML market. North America currently holds the largest share, but the Asia-Pacific region is the fastest-growing due to increased healthcare investment and awareness [7]. TERN-701’s global Phase 1 trial design and plans for dose-expansion data in Q4 2025 position it to enter these markets with robust evidence. The company’s upcoming 6-month MMR data will be a critical inflection point, offering clarity on durability of response and informing the path to a pivotal trial [1].

Competitive Threats and Mitigation

Despite its strengths, TERN-701 faces competition from both established players and emerging therapies. Novartis, Bristol-Myers Squibb, and Pfizer remain dominant with their TKI portfolios, while newer entrants like asciminib (Bristol-Myers Squibb) are gaining traction. However, TERN-701’s differentiated mechanism and superior safety profile in early trials provide a clear edge. Additionally, Terns’ focus on personalized treatment strategies, supported by collaborations like the iCMLf/HARMONY Genomics Project, underscores its commitment to data-driven care [8].

The obesity market, where Terns is pivoting for partnerships, adds another layer of complexity. While TERN-601’s oral formulation could disrupt a market dominated by injectables like Wegovy and Zepbound, the company’s decision to deprioritize this asset post-2025 reduces financial risk and allows it to concentrate on CML [6].

Conclusion: A Best-in-Class Contender

TERN-701’s clinical performance, strategic clarity, and alignment with market trends position Terns Pharmaceuticals as a formidable player in the CML space. With 6-month MMR data expected in late 2025 and a $315.4 million financial runway, the company is well-positioned to advance TERN-701 toward commercialization. For investors, the key question is whether the drug’s early promise translates into sustained efficacy and regulatory approval. If it does, TERN-701 could not only become a best-in-class therapy but also redefine the economics of CML treatment in the 2030s.

Source:
[1] Terns Pharmaceuticals Reports Second Quarter 2025 Financial Results [https://ir.ternspharma.com/news-releases/news-release-details/terns-pharmaceuticals-reports-second-quarter-2025-financial]
[2] Terns Pharmaceuticals: Assessing TERN-701's Potential to [https://www.ainvest.com/news/terns-pharmaceuticals-assessing-tern-701-potential-drive-valuation-investor-sentiment-2509/]
[3] Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a network meta-analysis [https://pmc.ncbi.nlm.nih.gov/articles/PMC11319984/]
[4] TERN-701 Shows Promising Early Results in Heavily Pre-Treated CML [https://www.targetedonc.com/view/tern-701-shows-promising-early-results-in-heavily-pre-treated-cml]
[5] TERN-701 Decreases BCR-ABL Levels, Generates Molecular Responses in R/R CML [https://www.onclive.com/view/tern-701-decreases-bcr-abl-levels-generates-molecular-responses-in-r-r-cml]
[6] Terns Pharmaceuticals (TERN): Evaluating the High ... [https://www.ainvest.com/news/terns-pharmaceuticals-tern-evaluating-high-potential-clinical-pipeline-strategic-path-creation-2509-65/]
[7] Chronic Myeloid Leukemia Treatment Market Size [https://market.us/report/chronic-myeloid-leukemia-treatment-market/]
[8] The iCMLf/HARMONY CML Genomics Project has Submitted Groundbreaking Research to the ASH 2025 Annual Meeting [https://www.facebook.com/icmlf/posts/the-icmlfharmony-cml-genomics-project-has-submitted-groundbreaking-research-to-t/1176880344466274/]