On November 14, 2023 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported financial results for the quarter ended September 30, 2023 and provided corporate updates (Press release, Terns Pharmaceuticals, NOV 14, 2023, View Source [SID1234637640]).
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"Throughout the third quarter and in recent weeks, we made meaningful progress across all three of our clinical development programs, opening U.S. Investigational New Drug (IND) applications, both for our allosteric BCR-ABL inhibitor TERN-701 for chronic myeloid leukemia (CML) and our lead small molecule oral GLP-1 agonist TERN-601 for obesity, and releasing Phase 2 data for our thyroid hormone receptor β agonist TERN-501 from the DUET study in NASH patients. We are now preparing for a data-rich 2024, with expected proof of concept readouts from our clinical trials in CML and obesity," stated Erin Quirk, MD, president and head of research and development at Terns. "The advances we are making, which are supported by strong clinical and scientific data, give us even greater confidence in our approach to bring better chemistry to the development of small-molecule candidates with clinically validated mechanisms to address oncologic and metabolic diseases with large unmet medical needs."
"We are excited to have dosed the first participant in our first-in-human trial of TERN-601 to treat obesity as preclinical data suggest it has potential for broad metabolic benefits in obesity, oral once-daily dosing, and suitability for combination therapy. We are also looking forward to dosing the first participants in our Phase 1 trial of TERN-701 as a treatment for CML while leveraging insights from our partner’s ongoing Phase 1 trial in China to support a starting dose that appears safe and clinically active based on emerging early clinical data," added Dr. Quirk.
Recent Pipeline Developments and Anticipated Milestones
TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for CML
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In October, Terns announced the Investigational New Drug (IND) clearance from the U.S. FDA and design of the CARDINAL Phase 1 clinical trial of TERN-701 for the treatment of CML
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CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK), and efficacy of TERN-701 in participants with previously treated CML
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The dose escalation portion (Part 1) of the trial will evaluate once-daily TERN-701 monotherapy in approximately 24-36 adults living with CML to be enrolled in up to five dose cohorts; screening for Part 1 is anticipated to begin in December 2023
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Primary endpoints of the CARDINAL dose escalation portion include incidence of dose limiting toxicities (DLTs) during the first treatment cycle and additional measures of safety and tolerability
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Secondary endpoints include PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels
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The starting dose is 160 mg QD (once-daily), with the option to explore a lower dose of 80 mg QD
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The dose expansion portion (Part 2) of the CARDINAL trial will initiate after dose escalation data are available and will enroll approximately 40 patients, randomized to once-daily treatment with one of two doses of TERN-701 to be selected based on data from Part 1
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The primary endpoint of the CARDINAL dose expansion portion is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK
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The CARDINAL trial plans to enroll at sites in the United States, Europe and other global territories
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Global site identification and trial start-up activities are ongoing, with interim top-line readouts from initial cohorts expected in the second half of 2024
TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity
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Earlier this month, Terns announced that the first participant was dosed in the Phase 1 first-in-human clinical trial of TERN-601 for obesity
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The Phase 1 trial is a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, PK and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or who are overweight
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Part 1 (SAD) is a SAD study that will evaluate up to six once-daily TERN-601 dose levels in approximately 40 healthy participants
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The starting TERN-601 dose is 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts
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Part 2 (MAD) of the trial will enroll approximately 72 obese and overweight healthy participants and will include cohorts incorporating titration of TERN-601 administered for 28-days at doses to be selected based on data from Part 1
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Top-line, 28-day proof of concept weight loss data from the Phase 1 trial is expected in the second half of 2024
TERN-501: Oral, thyroid hormone receptor-β (THR-β) agonist for NASH
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Phase 2a DUET trial data evaluating TERN-501 for the treatment of NASH was featured in an oral late-breaking presentation at The Liver Meeting 2023:
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The oral presentation titled, "Topline results from a 12-week Phase 2a Trial (DUET) evaluating TERN-501, a highly selective thyroid hormone receptor (THR) β agonist, either as monotherapy or in combination with TERN-101, a nonsteroidal farnesoid X receptor (FXR) agonist, demonstrated significant reductions in MR-based liver fat content and fibroinflammation in patients with presumed NASH," was delivered by Mazen Noureddin, MD, MHSc, Professor of Medicine, Academic Institute at Houston Methodist, Director of Houston Research Institute
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Terns reported positive top-line data from the Phase 2a DUET trial of TERN-501 for the treatment of NASH in August
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TERN-501 met all primary and secondary endpoints
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TERN-501 demonstrated dose dependent MRI-PDFF reductions at Week 12 as a once-daily, low dose, and combinable oral therapy
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TERN-501 (6 mg) showed statistically significant mean relative liver fat content reduction of 45% as assessed by MRI-PDFF with 64% of patients achieving >30% PDFF reduction
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All TERN-501 doses were well-tolerated with no gastrointestinal and no cardiovascular safety signals
Corporate Updates
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In August 2023, Terns announced the departure of Senthil Sundaram, the Company’s former chief executive officer, for health reasons. Terns is conducting an ongoing search for a permanent chief executive officer. In the interim, Dr. Quirk continues to assume day-to-day leadership of the Company and serve as principal executive officer. In addition, the Board has engaged board director, Jill M. Quigley, JD as senior advisor and strategy officer on an interim basis until a permanent chief executive officer is appointed.
Third Quarter 2023 Financial Results
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Cash Position: As of September 30, 2023, cash, cash equivalents and marketable securities were $266.6 million, as compared with $283.1 million as of December 31, 2022. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2026.
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Research and Development (R&D) Expenses: R&D expenses were $14.8 million for the quarter ended September 30, 2023, as compared with $12.2 million for the quarter ended September 30, 2022.
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General and Administrative (G&A) Expenses: G&A expenses were $18.4 million for the quarter ended September 30, 2023, as compared with $5.1 million for the quarter ended September 30, 2022.
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Net Loss: Net loss was $29.8 million for the quarter ended September 30, 2023, as compared with $16.8 million for the quarter ended September 30, 2022.