8-K: Terns Pharmaceuticals Announces Promising Early Data for TERN-701 in Chronic Myeloid Leukemia Trial

Terns Pharmaceuticals reported encouraging early results from its Phase 1 CARDINAL study of TERN-701, showing significant molecular responses and a favorable safety profile in patients with relapsed/refractory chronic myeloid leukemia.

Summary

• Terns Pharmaceuticals has released early data from the Phase 1 CARDINAL study of TERN-701, an investigational drug for chronic myeloid leukemia (CML).
• The study is evaluating TERN-701 in patients with relapsed or refractory CML who have previously been treated with other tyrosine kinase inhibitors (TKIs).
• The data, as of October 28, 2024, includes 15 patients across three dose levels: 160mg, 320mg, and 400mg.
• Patients in the study were heavily pre-treated, with a median of 4 prior TKIs and 80% having had 3 or more TKIs.
• The study showed an 88% decrease in BCR-ABL levels in patients with baseline transcript > 1%.
• A cumulative major molecular response (MMR) rate of 50% was observed in non-T315i mutation patients with 3 or more months of treatment.
• All patients with MMR or better at baseline maintained their response.
• The drug demonstrated a favorable safety profile with no dose-limiting toxicities, adverse event-related discontinuations, or serious adverse events.
• The study is on track to initiate dose expansion in the first half of 2025, with additional efficacy data expected in the fourth quarter of 2025.

Sentiment

Score: 8

Explanation: The document presents very positive early clinical data with strong efficacy and a favorable safety profile, suggesting a high potential for the drug. The management commentary is also very positive. However, it is still early-stage data, so there is some uncertainty.

Positives

• TERN-701 demonstrated compelling clinical activity with a 50% cumulative MMR rate at 3 months.
• The drug showed clinically meaningful molecular and hematologic responses in heavily pre-treated patients.
• The safety profile is encouraging, with no dose-limiting toxicities or serious adverse events.
• TERN-701 achieved high levels of target coverage with once-daily dosing.
• The study enrolled patients in all four dose escalation cohorts in less than a year, demonstrating excellent clinical and operational execution.

Negatives

• The data is from an early phase 1 trial and may not be indicative of future results.
• The study population was small, with only 15 patients enrolled in the initial dose escalation cohorts.
• The median treatment duration was only 3 months, so longer-term efficacy and safety data are still needed.

Risks

• The forward-looking statements are subject to risks and uncertainties that could cause actual results to vary materially.
• The success of the clinical trials is not guaranteed, and the drug may not receive regulatory approval.
• The company's ability to execute its development strategy and commercialize its product candidates is subject to various risks.
• The company's cash runway and sufficiency of its cash resources are subject to change.

Future Outlook

The company plans to initiate dose expansion cohorts in the first half of 2025 and expects to share additional safety and efficacy data, including longer-term MMR data, in the fourth quarter of 2025.

Management Comments

• Emil Kuriakose MD, chief medical officer of Terns, stated that the early data shows TERN-701 has compelling clinical activity with a highly encouraging cumulative MMR rate of 50% at 3 months.
• Amy Burroughs, chief executive officer of Terns, said that the data supports TERN-701's potential to be a best-in-class allosteric inhibitor for the treatment of CML.
• Amy Burroughs also highlighted the excellent clinical and operational execution at Terns, with patients enrolled in all four dose escalation cohorts in less than a year.

Industry Context

This announcement is significant in the context of CML treatment, as it presents a potential new option for patients who have failed other therapies. The positive early data suggests that TERN-701 could be a competitive alternative to existing BCR-ABL inhibitors.

Comparison to Industry Standards

• The 50% MMR rate at 3 months is a promising result, especially considering the heavily pre-treated patient population.
• Existing second-generation TKIs like nilotinib, dasatinib, and bosutinib have shown varying efficacy rates, and TERN-701's results appear competitive.
• The lack of dose-limiting toxicities and serious adverse events is also a positive differentiator compared to some existing treatments.
• Asciminib, a third-generation TKI, is a relevant comparator, and TERN-701's results suggest it could be a viable alternative, particularly for patients with resistance or intolerance to asciminib.

Stakeholder Impact

• Shareholders may react positively to the encouraging clinical data.
• Patients with CML may benefit from a new treatment option.
• Employees of Terns Pharmaceuticals may be motivated by the positive results.
• The company's partners may be encouraged by the progress of the clinical trial.

Next Steps

• The company will initiate dose expansion cohorts in the first half of 2025.
• Additional efficacy data, including longer-term MMR rates, is expected in the fourth quarter of 2025.

Key Dates

Keywords

TERN-701, Chronic Myeloid Leukemia, CML, BCR-ABL inhibitor, Tyrosine Kinase Inhibitor, TKI, CARDINAL study, Phase 1 trial, Molecular Response, MMR, Oncology, Clinical Trial