MK-4208 / Jiangsu Hansoh Pharma, Merck (MSD) - LARVOL DELTA

A Clinical Trial to Evaluate [14C]-MK-4208/[14C]-TERN-701 in Healthy Adult Male Participants (MK-4208-002/TERN701-1016) (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Terns, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

New P1 trial

A Clinical Trial to Evaluate MK-4208/TERN-701 in Healthy Adult Participants (MK-4208-001/TERN701-1014) (clinicaltrials.gov) - P1 | N=196 | Completed | Sponsor: Terns, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

New P1 trial

Safety and Efficacy of Tgrx-678, a Potent BCR::ABL1 allosteric Inhibitor, in Patients with Tyrosine Kinase Inhibitor Resistant and/or Intolerant Chronic Myeloid Leukemia: Updated Results of Phase 1 Study Tgrx-678 -1001 (ASH 2024) - P1, P2 | "Methods : In phase Ia, CML-CP and CML-AP patients who were R/I at least to imatinib, dasatinib and nilotinib were enrolled...Patients were heavily pretreated; 71 (66%) CP and 44 (88%) AP patients had received ≥ 3 prior TKIs; 40 (37%) CP and 30 (60%) AP patients had previously received ponatinib, olverembatinib, asciminib, and/or HS-10382 (a new STAMP inhibitor)...The updated data indicate promising efficacy in both CP and AP patients including those with the T315I mutation and those who failed 3G-TKI or STAMP inhibitors. Ongoing Phase 2 trials in China (NCT NCT06453902) and Phase 1 trials in US (NCT06088888) are further evaluating TGRX-678, underscoring the need for continued assessment."

Clinical • P1 data • Anemia • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hypertriglyceridemia • Leukopenia • Metabolic Disorders • Neutropenia • Thrombocytopenia • ABL1

A SINGLE-CENTER, CLINICAL STUDY EVALUATING THE EFFICACY AND SAFETY OF HS-10382 IN PATIENTS WITH NEWLY DIAGNOSED PHILADELPHIA-POSITIVE (PH+) CHRONIC MYELOID LEUKEMIA IN THE CHRONIC PHASE (CML-CP) (EHA 2026) - "In preclinical studies, HS-10382 demonstrated greater potency than the currently approved allosteric inhibitor, asciminib, against several BCR::ABL1 resistance mutations. Summary/Conclusion In this single-center study, HS-10382 demonstrated promising preliminary efficacy and favorable tolerability and safety at the dose of 160 mg BID in patients with newly diagnosed Ph+ CML-CP. These data support the further development of HS-10382 for the first- line treatment of CML-CP."

Clinical • Chronic Myeloid Leukemia • Dermatitis • Diabetes • Dyslipidemia • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Metabolic Disorders • Respiratory Diseases • ABL1

THE SAFETY, TOLERABILITY, AND EFFICACY OF HS-10382 COMBINED WITH FLUMATINIB IN PATIENTS WITH NEWLY DIAGNOSED PH+ CML: A PHASE 1B STUDY (EHA 2026) - "Summary/Conclusion HS-10382 in combination with flumatinib demonstrated a manageable safety profile and promising preliminary efficacy in patients with newly diagnosed CML-CP, characterized by rapid achievement and deepening of molecular responses. These findings support continued evaluation in an expanded cohort with longer follow-up to confirm the durability of deep molecular responses and long- term safety."

Clinical • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Chronic myeloid leukemia: incorporation of recent advances into current treatment algorithms. (PubMed, Blood Cancer J) - "In patients experiencing failure of frontline therapy due to resistance or intolerance, multiple second- and third-line options are available, including second-generation TKIs, ponatinib, and asciminib, as well as novel investigational agents, including the ABL1 kinase domain inhibitors olverembatinib and ELVN-001 and the STAMP inhibitors TGRX-678 and TERN-701. In this review, we discuss the recent advances in the treatment of CML-CP and challenge some established management practices."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Merck Completes Acquisition of Terns Pharmaceuticals, Inc. (Businesswire) - "Addition of TERN-701, a novel investigational oral allosteric BCR::ABL1 tyrosine kinase inhibitor, further diversifies Merck’s oncology pipeline...The transaction is expected to be accounted for as an asset acquisition, resulting in a charge to research and development expense of approximately $5.8 billion, or approximately $2.35 per share, included in both second quarter and full year 2026 GAAP and non-GAAP results. Additionally, GAAP and non-GAAP EPS are expected to be negatively impacted by approximately $0.12 per share in 2026, representing costs associated with advancing TERN-701 and costs of financing."

M&A • Chronic Myeloid Leukemia

Terns Pharmaceuticals, Inc…announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to TERN-701, a novel, oral allosteric BCR::ABL1 inhibitor, for the treatment of adult patients with Ph+ CML in the chronic phase without the T315I mutation previously treated with two or more TKIs. (Terns Press Release) - "TERN-701 BTD is based on data from the ongoing Phase 1/2 CARDINAL clinical trial of TERN-701 in patients with CML previously treated with at least one prior TKI and who experienced treatment failure, suboptimal response or treatment intolerance."

Breakthrough therapy • Chronic Myeloid Leukemia

Merck to Acquire Terns Pharmaceuticals, Inc., Expanding Its Hematology Pipeline With TERN-701, a Novel Candidate for Chronic Myeloid Leukemia (CML) (Terns Press Release) - "The transaction has been approved by both Merck’s and Terns’ Boards of Directors. Under the terms of the merger agreement, Merck, through a subsidiary, will acquire all of the outstanding shares of Terns. The acquisition is subject to a majority of Terns’ stockholders tendering their shares in a tender offer that will be initiated by a subsidiary of Merck....The transaction is expected to be accounted for as an asset acquisition and close in the second quarter of 2026, resulting in a charge of approximately $5.8 billion, or approximately $2.35 per share, included in both second quarter and full year 2026 GAAP and non-GAAP results."

M&A • Chronic Myeloid Leukemia

ADVANCES OF NEXT-GENERATION STAMP INHIBITORS IN CHRONIC MYELOID LEUKEMIA. (PubMed, Expert Opin Investig Drugs) - "Asciminib has shown efficacy in heavily pretreated patients and in the first-line setting, but resistance and limited benefit after ponatinib highlight the need for new therapeutic options...TGRX-678 exhibits potent activity against wild-type and mutant ABL1, including T315I, synergism with orthosteric tyrosine kinase inhibitors (TKIs), central nervous system (CNS) penetration, and encouraging phase Ia/Ib clinical activity in heavily pretreated CML. Early but promising data are also emerging for TERN-701 from the CARDINAL trial...Key questions regarding durability, long-term safety, and optimal integration with ATP-competitive TKIs remain open. Ongoing trials will define the clinical role of these STAMPi and their potential to advance cure-directed strategies, including treatment-free remission."

Journal • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL) (clinicaltrials.gov) - P1/2 | N=180 | Recruiting | Sponsor: Terns, Inc. | Phase classification: P1 ➔ P1/2 | N=100 ➔ 180 | Trial completion date: May 2026 ➔ May 2030 | Trial primary completion date: Nov 2025 ➔ Nov 2029

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

CARDINAL: A Phase 1 study of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor for patients with previously treated CML (ASH 2025) - P1 | "Herewe report initial results from the ongoing Phase 1 study of TERN-701 in pts with previously treated CML-CP. CARDINAL (NCT06163430) is an ongoing, open-label, two-part, global, multicenter Phase 1study in pts ≥18 years old with BCR::ABL1-positive CML-CP (with or without T315I mutation and withoutmyristoyl binding pocket mutations) previously treated with ≥1 prior second-generation (2G) TKI(bosutinib, dasatinib, or nilotinib)...Baseline characteristics included: median 3 prior TKIs (range: 1‒6); 35% had ≥4 prior TKIs; 36% had prior asciminib; 25% had prior ponatinib and/or investigational TKI(olverembatinib/ELVN-001); 56% had baseline BCR::ABL1>1%, with 44% having baseline BCR::ABL1>10%; and 13% with BCR::ABL1 mutations (9% T315I, 4% F317L)... TERN-701 demonstrated encouraging safety/tolerability and efficacy in a heavily pre-treatedpatient population with CML-CP previously treated with approved 1G/2G TKIs, ponatinib, asciminib, andother investigational,..."

Clinical • P1 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia

Efficacy of tgrx-678, a potent BCR::ABL1 allosteric inhibitor, in CML-CP and CML-AP patients harboring T315I mutation: Results from a phase 1 study (ASH 2025) - P1 | "35(66%) ptsreceived ≥ 3 prior TKIs; 24(45%) pts previously received ponatinib, olverembatinib, asciminib, and/or HS-10382 (STAMP inhibitor). Our study demonstrated that TGRX-678 achieved strong efficacy in patients with T315I-mutated CML in chronic or accelerated phase, with no clear dose–response relationship observed. Theseresults suggest that lower doses of TGRX-678 may offer comparable efficacy with potentially improvedsafety, particularly in heavily pretreated patients harboring T315I mutations."

Clinical • P1 data • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hypertriglyceridemia • Leukopenia • Metabolic Disorders • Neutropenia • Thrombocytopenia • ABL1

Terns Highlights Additional Positive Phase 1 Clinical Data Supporting TERN-701’s Best-in-Disease Potential in Relapsed/Refractory CML at the 67th ASH Annual Meeting (GlobeNewswire) - "As of the September 13, 2025 cutoff date, 63 patients were enrolled....Of 38 efficacy-evaluable patients: Overall (cumulative) MMR rate of 74% (28/38) by 24 weeks, with 64% (18/28) achieving MMR and 100% (10/10) maintaining MMR. MMR overall and achieved by 24 weeks in difficult to treat patient subgroups: Lack of efficacy to last tyrosine kinase inhibitor (TKI): 65% (13/20) overall; 63% (12/19) achieved....Assessment of patient cohorts at doses ≥ 320mg QD (n=53):...In 30 efficacy evaluable patients, overall MMR rate of 80% (24/30) by 24 weeks, with 75% (18/24) achieving MMR and 100% maintaining MMR (6/6)."

P1 data • Chronic Myeloid Leukemia

Tern-701 (HS-10382) Is a Potent Inhibitor of BCR: : ABL1 and Is Synergistic with Active Site Tyrosine Kinase Inhibitors (ASH 2023) - "Prospective mutagenesis experiments were conducted by treating BaF/3 cells engineered to overexpress the BCR: : ABL1 kinase with various concentrations of both TERN-701 and the TKI imatinib, followed by observation of clonal outgrowth of treated cells over time...Against a panel of cancer cell lines, TERN-701 was more selective than the comparator allosteric BCR: : ABL1 inhibitor asciminib while maintaining similar potency...Here, expanded studies using KCL22-s and BCR: : ABL1-T315I mutant cell lines identified strong synergistic interactions between TERN-701 and active site TKIs, including ponatinib and dasatinib...TERN-701 is a potent and highly selective allosteric inhibitor of BCR: : ABL1 that can act synergistically with active site TKIs in vitro, even against the T315I gatekeeper mutation that confers resistance to all approved active site TKIs except ponatinib, which has known safety liabilities. These data support the continued development of TERN-701 for the..."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Cardinal: A Phase I, Multicenter, Open-Label, Dose-Escalation and Dose-Optimization Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tern-701 in Chronic Myeloid Leukemia (ASH 2024) - P1 | "CARDINAL (NCT06163430) is an open-label, global, two-part, Phase I study evaluating the safety, tolerability, PK, and efficacy of TERN-701 in patients with previously treated CP-CML.Methods : Eligible patients are ≥18 years old with an Eastern Cooperative Oncology Group performance status of 0-2; a confirmed diagnosis of BCR : : ABL1-positive CP-CML, with or without the T315I mutation; and treatment failure on or intolerance of ≥1 prior second-generation TKI (dasatinib, nilotinib, or bosutinib). Patients intolerant of asciminib without overt resistance are eligible...Primary endpoints of Part 2 will measure efficacy, including hematologic response, molecular response, and best categorical shift in BCR : : ABL1 transcript levels from baseline; secondary endpoints will include safety, tolerability, and PK. The study is being conducted in the US, Europe, Australia and South Korea and currently open to enrollment."

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Terns Announces Abstract with Positive Clinical Data for TERN-701 in Relapsed/Refractory CML Selected for Oral Presentation at 67th ASH Annual Meeting (GlobeNewswire) - "Of 32 efficacy-evaluable patients: Overall (cumulative) major molecular response (MMR) rate of 75% (24/32) by 24 weeks, with 64% (14/22) achieving MMR and 100% (10/10) maintaining MMR; Overall (cumulative) MMR by 24 weeks in difficult to treat patient subgroups: (i) 69% (11/16) in patients with lack of efficacy to last tyrosine kinase inhibitor (TKI); (ii) 60% (6/10) in patients who had prior asciminib; (iii) 67% (8/12) in patients with prior asciminib / ponatinib / investigational TKI."

P1 data • Chronic Myeloid Leukemia

Reiterates focus on TERN-701… (GlobeNewswire) - "'We look forward to announcing new data from our Phase 1 CARDINAL trial of TERN-701 for CML this quarter'."

P1 data • Chronic Myeloid Leukemia

Characterization and Efficacy of TERN-701 in Pre-Clinical Models of Chronic Myeloid Leukemia (SOHO 2025) - "TERN-701 exhibited greater potency than asciminib in most cases and was highly selective for BCR::ABL1. Activity against active-site and A-loop mutations, Ceffective potencies, and drug-like properties support the potential efficacy of TERN-701 in CML patients that are resistant or intolerant to other lines of therapy. Oral presentation at the European Hematology Association annual congress, June 13, 2025."

Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL2

Effect of TERN-701 on Transporter and Cytochrome P450 Probe Substrates and the Effect of Acid-Reducing Agents on TERN-701 Pharmacokinetics (SOHO 2025) - "All study treatments were well tolerated. TERN-701 is not a clinically relevant inhibitor of CYP3A4, CYP2C8, CYP2C19, or OATP1B1/3. TERN-701 is not sensitive to changes in gastric pH."

PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CYP2C19 • CYP3A4

Terns Pharmaceuticals to Host an Educational Webinar on TERN-701 for Investors in Advance of Phase 1 Data Expected in Fourth Quarter 2025 (GlobeNewswire) - "The webinar will review TERN-701’s potential best-in-class profile, relevant benchmarks for upcoming Phase 1 data and positioning in an evolving treatment landscape for chronic myeloid leukemia (CML)."

P1 data • Chronic Myeloid Leukemia

Activity of STAMP inhibitors in ABL2 rearranged acute lymphoblastic leukemia is dependent on the Abl2 SH3 domain. (PubMed, Blood Neoplasia) - "In this study, we extended these in vitro findings to demonstrate similar sensitivity to the second-generation STAMP inhibitor, TERN-701, using ZC3HAV1::ABL2 ALL cells. Importantly, this suggests that, in the clinical setting, different asciminib binding site mutations may be anticipated with STAMP treatment for ABL2r ALL. Finally, we demonstrated the efficacy of both STAMP inhibitors against cells from patients with ZC3HAV1::ABL2 and asciminib as a novel treatment for ZC3HAV1::ABL2 disease in a preclinical in vivo study."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL2

Management of chronic myeloid leukemia in 2025. (PubMed, Cancer) - "Today, the six approved BCR::ABL1 TKIs, five in frontline therapy (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and all six in later line therapy (including ponatinib), fulfill in one form or another these requirements. Third-generation TKIs that target the ABL1 kinase domain (olverembatinib and ELVN-001) or the myristoyl pocket (TGRX-678 and TERN-701) are under development...However, serious complications, such as graft-vs-host disease, or death could occur. This review summarizes relevant information concerning the management of CML in 2025, and addresses some CML treatment pathways that became entrenched in the management of CML in the first 15-20 years of TKI experience, which may need to be revisited."

Journal • Review • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • ABL1

CHARACTERIZATION & EFFICACY OF TERN-701 IN PRE-CLINICAL MODELS OF CHRONIC MYELOID LEUKEMIA (EHA 2025) - P1 | "TERN-701 exhibited greater potency than asciminib in most cases. TERN-701 is currently being evaluated in the CARDINAL trial (NCT06163430), a multi-center dose-escalation & dose-expansion phase 1, to assess safety, tolerability, and efficacy in patients with previously treated chronic phase (CP) CML. Importantly, converting in vitro potencies to plasma concentrations supports the potential efficacy of TERN-701 in a wide range of patients, including those resistant or intolerant to other lines of therapy, with the proposed clinical doses providing extended coverage of various mutations such as T315I & M244V. These data support the development of TERN-701 as a potential best-in-class therapy for treating CML."

Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL2

Terns Pharmaceuticals Selected for Oral Presentation at European Hematology Association Congress For Preclinical Data on Novel Allosteric BCR-ABL Inhibitor TERN-701 (GlobeNewswire) - "The preclinical data to be presented highlight the potency of TERN-701 on more than 20 clinically relevant resistance mutations in the active-site, P-loop, and allosteric regions of the BCR-ABL oncoprotein, and provide additional data characterizing the drug-like properties of TERN-701 and supporting the potential to provide meaningful clinical benefits over existing therapies."

Preclinical • Oncology