TERN-701Bcr-Abl CML Drug Profile
TERN-701
Bcr-Abl CML Drug Profile
TERN-701 is a small molecule drug targeting Bcr-Abl, developed by Terns Pharmaceuticals, Inc. On April 27, 2026, it was granted Breakthrough Therapy designation in the United States for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
Breakthrough Therapy designation for Ph+ CML in chronic phase — April 2026
TERN-701 is a small molecule drug targeting Bcr-Abl (BCR-ABL fusion protein), developed by Terns Pharmaceuticals, Inc. On April 27, 2026, it was granted Breakthrough Therapy designation in the United States for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. This designation reflects serious unmet need in a patient population where resistance to existing BCR-ABL tyrosine kinase inhibitors remains a central clinical challenge.
| Drug name | TERN-701 |
| Target | Bcr-Abl (BCR-ABL fusion tyrosine kinase) |
| Drug type | Small molecule drug |
| Developer | Terns Pharmaceuticals, Inc. |
| Indication | Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase |
| Designation | Breakthrough Therapy designation (United States) |
| Designation date | April 27, 2026 |
| Patents | 1 |
| Clinical trials | 4 (Neoplasms) |
4 clinical trials in Neoplasms, 1 patent
According to the Synapse database, TERN-701’s development program primarily focuses on the field of Neoplasms. A total of 4 clinical trials have been conducted. According to the Synapse database, there is 1 patent associated with TERN-701 — reflecting a program at an early IP registration stage consistent with its Phase 1/2 development status at the time of BTD designation.
BCR-ABL: constitutively active fusion kinase driving Philadelphia chromosome-positive leukemia
Chronic myeloid leukemia in chronic phase (CP-CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, a reciprocal translocation between chromosomes 9 and 22 that generates the oncogenic BCR-ABL1 fusion gene. This abnormal fusion protein functions as a constitutively active tyrosine kinase, driving uncontrolled proliferation of myeloid cells, reduced apoptosis, and altered bone marrow signaling pathways. The chronic phase represents the earliest and most stable stage of the disease, during which leukemic cells retain partial differentiation capacity. Common symptoms include fatigue, weight loss, night sweats, fever, splenomegaly, abdominal discomfort, easy bruising, and elevated white blood cell counts, although some patients are asymptomatic at diagnosis. Epidemiologically, CML accounts for approximately 15–20% of adult leukemias worldwide, with an annual incidence of about 1–2 cases per 100,000 individuals. The introduction of BCR-ABL tyrosine kinase inhibitors has dramatically improved long-term survival and transformed CP-CML into a largely manageable chronic condition for many patients.
BCR-ABL: constitutively active fusion kinase from the Philadelphia chromosome
BCR-ABL fusion protein is an oncogenic fusion tyrosine kinase generated by the reciprocal translocation t(9;22)(q34;q11), known as the Philadelphia chromosome, which fuses the BCR gene on chromosome 22 with the ABL1 proto-oncogene on chromosome 9. The fusion protein retains the coiled-coil oligomerization domain of BCR and the SH1 tyrosine kinase domain, SH2/SH3 regulatory domains, and actin-binding regions of ABL1, resulting in constitutive kinase activation independent of normal cellular regulation.
BCR-ABL · Fusion kinase · Philadelphia chromosomeRAS/RAF/MEK/ERK, PI3K/AKT/mTOR, JAK/STAT: multi-pathway oncogenic activation
BCR-ABL drives malignant transformation by promoting uncontrolled proliferation, inhibiting apoptosis, altering cell adhesion, and enhancing genomic instability. The fusion kinase activates multiple downstream signaling pathways: RAS/RAF/MEK/ERK for cell proliferation, PI3K/AKT/mTOR for survival and metabolism, JAK/STAT for cytokine-independent growth, and SRC family kinase signaling involved in leukemic progression and resistance. Persistent activation of these pathways is central to the pathogenesis of Philadelphia chromosome-positive leukemias.
RAS/RAF · PI3K/AKT · JAK/STAT · SRC kinasePhase 1/2 study in participants with chronic myeloid leukemia
The clinical trial supporting TERN-701’s Breakthrough Therapy designation is a Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia. The Phase 1/2 design is standard for early-stage oncology programs receiving BTD, where preliminary evidence of substantial improvement over existing therapies can qualify for designation before completion of pivotal Phase 3 registration trials.
| Phase | Phase 1/2 |
| Design | Safety, Tolerability, Pharmacokinetics, and Efficacy evaluation |
| Population | Participants with Chronic Myeloid Leukemia |
178 drugs targeting Bcr-Abl — TERN-701 entering a mature but evolving class
According to the Synapse Database, there are currently 178 drugs targeting Bcr-Abl. TERN-701 enters a competitive class anchored by multiple approved TKIs but with ongoing unmet need in resistant and intolerant patient populations.
178 Bcr-Abl drugs: a mature class with ongoing resistance-driven innovation
The 178-drug BCR-ABL targeting landscape spans multiple approved TKI generations (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminib) and a broad pipeline of investigational compounds. Each successive generation has addressed resistance mutations — particularly T315I — generated by prior TKI therapy. TERN-701’s BTD in CP-CML positions it within this ongoing resistance-management paradigm in the BCR-ABL inhibitor class.
BTD in CP-CML: FDA signalling substantial improvement potential
TERN-701’s Breakthrough Therapy designation for CP-CML indicates FDA’s assessment that preliminary clinical evidence shows substantial improvement over available therapy. In the CML context — where multiple approved TKIs exist — BTD typically signals either a superior resistance profile, improved tolerability, or efficacy in a patient subset (e.g. TKI-intolerant or multiply-resistant patients) where current options are inadequate.
Terns Pharmaceuticals: early-stage IP position with 1 patent at BTD stage
With 1 patent associated with TERN-701 at the time of its April 2026 BTD, Terns Pharmaceuticals is at an early IP registration stage relative to the established BCR-ABL TKI class. This is consistent with a program at Phase 1/2 where primary patent filings covering the novel compound and initial therapeutic claims are typically in place, with additional method-of-use and formulation patents pending or planned.
Multi-pathway oncogenic signalling: the therapeutic rationale for continued BCR-ABL drug development
BCR-ABL’s activation of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, JAK/STAT, and SRC kinase pathways means that TKI resistance can arise through multiple mechanisms: kinase domain mutations, pathway bypass, clonal evolution, and microenvironmental factors. This multi-pathway complexity sustains demand for new BCR-ABL inhibitors with differentiated mutation coverage or mechanism, underpinning the continued 178-drug pipeline activity in this target class.
TERN-701 — key questions answered
TERN-701 is a small molecule drug targeting Bcr-Abl developed by Terns Pharmaceuticals, Inc. On April 27, 2026, it was granted Breakthrough Therapy designation in the United States for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
According to the Synapse database, TERN-701 has been studied in 4 clinical trials, primarily in the field of Neoplasms.
According to the Synapse database, there is 1 patent associated with TERN-701.
Chronic myeloid leukemia in chronic phase (CP-CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, a reciprocal translocation between chromosomes 9 and 22 that generates the oncogenic BCR-ABL1 fusion gene. This abnormal fusion protein functions as a constitutively active tyrosine kinase, driving uncontrolled proliferation of myeloid cells. CML accounts for approximately 15–20% of adult leukemias worldwide, with an annual incidence of about 1–2 cases per 100,000 individuals.
The pivotal trial for TERN-701 is a Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia.
According to the Synapse Database, there are currently 178 drugs targeting Bcr-Abl.
Data on this page is sourced from the PatSnap Synapse database and the April 2026 monthly pharmaceutical report. Represents a snapshot of available records as of April 2026.