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

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

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

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 Disorders • Hematological Malignancies • Leukemia • Oncology

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

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 (EHA 2024) - P1 | " Eligible patients are ≥18 years old with an Eastern Cooperative Oncology Group performance status of 0–2; aconfirmed diagnosis of BCR::ABL1–positive CP CML, with or without the T315I mutation; and treatment failureon or intolerance of ≥1 prior second-generation TKIs (dasatinib, nilotinib, or bosutinib). None, trial in progress."

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

Terns Pharmaceuticals Reports First Quarter 2024 Financial Results and Corporate Updates (GlobeNewswire) - "Terns’ Phase 1 CARDINAL trial of TERN-701 in CML is ongoing and interim data from initial CARDINAL dose escalation cohorts are expected in the second half of 2024."

P1 data • Trial status • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Terns Pharmaceuticals Announces Data from Ongoing Phase 1 Pharmacokinetic Study of Allosteric BCR-ABL Inhibitor TERN-701 in Adult Healthy Volunteers and Highlights Potential for Competitive Differentiation (GlobeNewswire) - P1 | N=32 | "Terns Pharmaceuticals...announced findings from a Phase 1 study of TERN-701 in Western healthy volunteers....The Phase 1 single-ascending dose (SAD) trial is ongoing in the United States and has enrolled 32 healthy volunteers in four dose escalation cohorts of eight participants each to evaluate PK, food effect and safety and tolerability at single doses ranging from 20 mg to 160 mg. No clinically meaningful changes or trends were observed in clinical laboratory data, vital signs or electrocardiogram (ECG) parameters at any dose level. Across the dose range administered to date, TERN-701 PK was linear with a median half-life ranging from 8 to 12 hours....Phase 1 CARDINAL trial evaluating TERN-701 in 2L+ CML patients remains ongoing, with interim data from initial cohorts anticipated in second half of 2024."

P1 data • PK/PD data • Trial status • Chronic Myeloid Leukemia

Terns Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Updates (GlobeNewswire) - "TERN-701: Interim data from initial CARDINAL dose escalation cohorts expected in the second half of 2024."

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

Terns Pharmaceuticals Announces Orphan Drug Designation Granted to TERN-701 for the Treatment of Chronic Myeloid Leukemia (GlobeNewswire) - "Terns Pharmaceuticals, Inc....today announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TERN-701 for the treatment of chronic myeloid leukemia (CML). TERN-701, the Company’s internally discovered allosteric BCR-ABL tyrosine kinase inhibitor (TKI), is in Phase 1 clinical development with interim data from initial dose escalation cohorts expected in the second half of 2024."

Orphan drug • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

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=80 | Not yet recruiting | Sponsor: Terns, Inc.

New P1 trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

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

Terns Pharmaceuticals Announces Global Phase 1 Clinical Trial Design of TERN-701 for the Treatment of Chronic Myeloid Leukemia (GlobeNewswire) - "Terns Pharmaceuticals, Inc...announced the U.S. Food and Drug Administration’s (FDA’s) clearance of the Company’s Investigational New Drug application and the design of the CARDINAL Trial, Terns’ global Phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of TERN-701 in participants with chronic myeloid leukemia (CML)...The CARDINAL Trial plans to enroll at sites in the U.S., Europe and other Terns global territories. Global site identification and trial start-up activities are ongoing, with the first patient screening expected in December 2023....Terns anticipates initiation of the CARDINAL Trial, a global Phase 1 trial for TERN-701, in the second half of 2023, with potential interim top-line readouts from initial cohorts in 2024."

IND • New P1 trial • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

The Novel BCR::ABL1 Allosteric Inhibitor HS‑10382/TERN‑701 is Potent Against Mutations Resistant to Active Site Tyrosine Kinase Inhibitors (TKIs) and Acts Synergistically With TKIs in BCR::ABL1+ Cancer Cell Lines (SOHO 2023) - "TERN-701/HS-10382 is a potent and selective allosteric inhibitor of BCR::ABL1 in cell- free and cell-based assays and screens, with comparable potency and synergy profiles to that of asciminib while potentially being more selective. TERN-701/HS-10382 retains activity against the T315I gatekeeper mutation, which confers resistance to all approved active site TKIs except for ponatinib, which has known safety liabilities. These data support the continued development of TERN-701/ HS-10382 for the treatment of CML."

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

Terns Pharmaceuticals Reports Second Quarter 2023 Financial Results and Corporate Updates (GlobeNewswire) - "TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML): Terns expects to initiate a clinical trial for TERN-701 in the second half of 2023, with potential interim top-line readouts from initial dose-escalation cohorts in 2024. Terns has completed drug manufacturing to enable the initiation of its Phase 1 trial for TERN-701. The Phase 1 trial for TERN-701 is expected to include sites from the U.S., Europe and other countries."

Commercial • New P1 trial • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Terns Pharmaceuticals to Host Virtual Key Opinion Leader Event to Discuss TERN-701 and Advances in the Treatment Landscape for Chronic Myeloid Leukemia (GlobeNewswire) - "Terns Pharmaceuticals...announced it will host a virtual key opinion leader event to highlight the TERN-701 program and discuss advances in the treatment landscape for chronic myeloid leukemia (CML)....The event will be led by Emil Kuriakose, M.D., chief medical officer, oncology, at Terns and will feature presentations..."

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

A PHASE 1 MULTICENTER OPEN-LABEL DOSE-ESCALATION AND DOSE- EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, EFFICACY OF HS-10382 (TERN-70) IN CHRONIC MYELOID LEUKEMIA PATIENTS (EHA 2023) - P1 | "This study is ongoing (enrollment underway for Part 1, dose 3 as of February 2023) with 7 participating study sites in China. Clinical trial information: NCT05367700. Phase I, Chronic myeloid leukemia, BCR-ABL"

Clinical • P1 data • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

A phase 1, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10382 (TERN-701) in patients (pts) with chronic myeloid leukemia (CML). (ASCO 2023) - P1 | "This study is ongoing (enrollment underway for Part 1, dose 3 as of February 2023) with 7 participating study sites in China. Clinical trial information: NCT05367700."

Clinical • P1 data • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Terns Pharmaceuticals Announces Publication of TERN-701 Trial-in-Progress Abstract for the 2023 ASCO Annual Meeting (GlobeNewswire) - "Terns Pharmaceuticals...announced that the TERN-701 (HS-10382) trial-in-progress (TiP) abstract is now available on the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting website. The ASCO Annual Meeting will be held in person at McCormick Place in Chicago, Illinois, and online from June 2 - 6, 2023. The TiP abstract details that patient enrollment reached Cohort 3 of the Dose Escalation phase as of February 2023, with seven participating study sites in China. The TiP poster highlights completion of enrollment of Cohort 5 as of April 2023."

Trial status • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology