TERN-701 / Jiangsu Hansoh Pharma, Terns Pharma - LARVOL DELTA

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

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

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

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

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

Terns Pharmaceuticals Reports First Quarter 2025 Financial Results and Provides Corporate Updates (GlobeNewswire) - "Recent Clinical Pipeline Developments and Anticipated Milestones: (i) TERN-701: Oral, small-molecule next-generation allosteric BCR-ABL inhibitor for chronic myeloid leukemia (CML): In April 2025, Terns enrolled the first patient in the dose expansion portion of the Phase 1 CARDINAL study of TERN-701 for CML....Terns plans to report additional safety and efficacy data from the dose escalation and expansion portions of the study in 4Q 2025."

P1 data • Trial status • Chronic Myeloid Leukemia

Terns Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Corporate Updates (GlobeNewswire) - "The dose expansion portion of the Phase 1 CARDINAL study is expected to initiate in the second quarter of 2025 with additional safety and efficacy data expected in the fourth quarter of 2025...Data expected to include a larger cohort of patients with longer durations of treatment and read through to approval endpoint of 6-month major molecular response (MMR)"

P1 data • Trial status • Chronic Myeloid Leukemia

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML) (GlobeNewswire) - "Dose escalation in Phase 1 CARDINAL study is complete as of January 2025, with dose expansion portion expected to initiate in the second quarter of 2025...Additional safety and efficacy data are expected in the fourth quarter of 2025."

P1 data • Trial status • Chronic Myeloid Leukemia

CARDINAL- A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Terns, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Terns Pharmaceuticals Announces Positive Early Data from Phase 1 CARDINAL Trial of TERN-701 for Chronic Myeloid Leukemia (GlobeNewswire) - P1 | N=80 | CARDINAL (NCT06163430) | Sponsor: Terns, Inc. | "Terns Pharmaceuticals, Inc...announced encouraging early data from the ongoing dose escalation part of the Phase 1 CARDINAL study evaluating TERN-701 in patients with relapsed/refractory chronic myeloid leukemia (CML)....88% (7/8) of patients with baseline transcript > 1% had decreases in BCR-ABL on treatment, with 7 ongoing as of data cutoff; Cumulative MMR rate of 50% (5/10) in non-T315i mutation patients with 3 or more months of treatment and/or MMR or better at baseline; 100% (4/4) of patients with MMR or better at baseline have maintained their response and remain on treatment....Steady state PK data, available for the 160mg and 320mg dose levels at data cutoff, showed linear PK with dose proportional increases in exposure. Plasma protein binding-corrected Caverage for TERN-701 exceeded the in vitro IC90 for multiple mutated and non-mutated BCR-ABL variants with once daily dosing." .

P1 data • Chronic Myeloid Leukemia

A Study to Evaluate the Efficacy and Safety of HS-10382 in Patients with Newly Diagnosed ChronicPhase Chronic Myeloid Leukemia. (ChiCTR) - P=N/A | N=20 | Recruiting | Sponsor: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

New trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, Tolerability, Pharmacokinetics, and the Effect of Food on TERN-701, an Oral Allosteric BCR-ABL Tyrosine Kinase Inhibitor, in Healthy Participants (SOHO 2024) - "TERN-701 was well tolerated following single dosing up to 160 mg. Preliminary results of the food-effect evaluation support dosing of TERN-701 without regard to food. The PK and safety profile of TERN-701 support further development in CML with once-daily dosing."

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

CARDINAL: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Dose-Optimization Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Chronic Myeloid Leukemia (SOHO 2024) - P1 | " 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/intolerance of ≥1 prior second- generation TKI (dasatinib, nilotinib, or bosutinib). Patients intolerant of asciminib without overt resistance are eligible...Part 2 primary endpoints will measure efficacy (hematologic response, molecular response, and best categorical shift in BCR::ABL1 transcript levels from baseline); secondary endpoints include safety, tolerability, and PK. The study is being conducted in the US, Europe, Australia, and South Korea."

Clinical • P1 data • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Terns Pharmaceuticals Reports Second Quarter 2024 Financial Results and Corporate Updates (GlobeNewswire) - "Interim data from initial dose escalation cohorts in Terns’ ongoing Phase 1 CARDINAL trial of TERN-701 in CML expected in December 2024; Terns plans to host a TERN-701-focused virtual key opinion leader (KOL) event on August 20, 2024 at 10am ET."

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

Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML) (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Combination therapy • New P1 trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology