Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity.
The company’s programs are based on mechanisms of action that have achieved proof-of-concept in clinical trials in indications with significant unmet medical needs. The company is advancing multiple drug candidates that have the potential to deliver improved clinical outcomes in the target indication as...
Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity.
The company’s programs are based on mechanisms of action that have achieved proof-of-concept in clinical trials in indications with significant unmet medical needs. The company is advancing multiple drug candidates that have the potential to deliver improved clinical outcomes in the target indication as either single-agent or combination therapies. The most advanced product candidates in the company’s pipeline – TERN-701, TERN-601 and TERN-501 – were internally discovered. Additionally, the company has an ongoing discovery effort for the TERN-800 series of small-molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators for obesity, which have the potential to be combined with glucagon-like peptide-1 (GLP-1) receptor agonists, such as TERN-601.
Pipeline Candidate in Oncology
TERN-701 is the company’s proprietary, oral, potent, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) specifically targeting the ABL myristoyl pocket for CML, a form of cancer that begins in the bone marrow and leads to the growth of leukemic cells and is classified as an orphan indication. Terns previously announced positive early data from the Phase 1 CARDINAL trial of TERN-701, demonstrating compelling molecular responses and an encouraging safety profile with no dose limiting toxicities (DLTs), adverse event (AE)-related treatment discontinuations or dose reductions across all dose escalation cohorts. Additional safety and efficacy data from CARDINAL are expected in the fourth quarter of 2025.
Pipeline Candidates for Metabolic Diseases
TERN-601 is the company’s small-molecule GLP-1 receptor agonist that is intended to be orally administered once-daily for obesity. Obesity is a chronic disease that is increasing in prevalence in adults, adolescents and children and is often defined by having an elevated body mass index (BMI) of 30 or greater. Terns previously announced positive results from the Phase 1 trial of TERN-601, demonstrating weight loss over 28 days up to 5.5% and favorable safety and tolerability despite rapid dose titration every three days. The Phase 2 FALCON trial of TERN-601 initiated with the first patient enrolled in March 2025, and 12-week data are expected in the fourth quarter of 2025.
TERN-501 is the company’s thyroid hormone receptor beta (THR-Beta) agonist initially developed for metabolic dysfunction-associated steatohepatitis (MASH). Since announcing positive top-line data from the Phase 2a DUET trial in August 2023, the company decided to limit spend in the development of TERN-501 for MASH given the current regulatory and clinical development requirements for the indication. The company continues to evaluate opportunities for TERN-501 in other metabolic diseases.
TERN-800 series is the company’s ongoing effort to discover small molecule GIPR modulators for obesity, which has the potential for combination with GLP-1 receptor agonists, such as TERN-601. The company is prioritizing its discovery efforts towards nominating a GIPR antagonist development candidate based on in-house discoveries and growing specific scientific rationale supporting the potential of GLP-1 receptor agonist and GIPR antagonist combinations for obesity.
Solution for BCR-ABL TKIs
TERN-701 intends to address the limitations of active-site TKIs with the goal of achieving improved tumor suppression through a combination of (1) improved efficacy against BCR-ABL, including a broad range of mutations, (2) improved safety and tolerability profiles, and an improved drug-drug interaction profile, and (3) improved convenience with once-a-day dosing for all patients, with or without food. Supporting efficacy data include numerically greater potency than asciminib against multiple BCR-ABL variants, improved pharmacokinetic (PK) and target coverage over asciminib and rescue of clinical response in asciminib failures. TERN-701 has also demonstrated a promising safety profile relative to asciminib, with no DLTs and no AE-related treatment discontinuations or dose reductions in the dose escalation phase of the company’s Phase 1 trial. In healthy volunteer studies, TERN-701 also demonstrated the ability to be dosed once-daily without regard to food, as well as a favorable drug-drug interaction profile, which represents potential key differentiators over asciminib.
Given the emerging clinical profile, TERN-701 has broad opportunities across front- and second-line patient settings. In the front-line, where the allosteric class has demonstrated improvements over active-site TKIs, TERN-701 is building a differentiated profile that has the potential to offer improved efficacy, safety and convenience compared to asciminib. As a result, if TERN-701 successfully completes clinical development and is approved for marketing, the company has an opportunity to potentially treat a significant share of newly diagnosed patients. The company anticipate that there will be a meaningful share of front-line patients starting on a generic active-site TKI due to cost. Based on historical data, approximately 40% of those who started on an active-site TKI will need to switch therapies due to suboptimal response and/or tolerability and are likely to switch to an allosteric TKI. If approved for marketing, that TERN-701 can be positioned as the allosteric TKI of choice for all patients switching to an allosteric TKI. In the Phase 1 data to date, TERN-701 demonstrated compelling molecular responses in patients who have experienced suboptimal response or intolerance to active-site TKIs and asciminib. Physicians and people with CML continue to seek novel therapies that provide improved efficacy, safety and convenience.
Clinical development of TERN-701
In July 2020, Hansoh (Shanghai) Healthtech Co., Ltd. and Jiangsu Hansoh Pharmaceutical Group Company Ltd. (collectively, Hansoh) in-licensed TERN-701 for development in the greater China region. TERN-701 is referred to by Hansoh as HS-10382. In May 2022, Hansoh initiated an open-label, multicenter, dose-escalation and expansion, first-in-human study in chronic or accelerated phase CML patients, who are resistant or intolerant to prior active-site BCR-ABL TKI treatment. Hansoh is responsible for all development costs in the greater China region, including the ongoing Phase 1 trial in China.
The company’s Phase 1 trial, CARDINAL, is progressing and includes sites from the United States, Europe and other countries. The FDA granted Orphan Drug Designation for TERN-701 for the treatment of chronic myeloid leukemia in March 2024.
The CARDINAL trial is an ongoing global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, PK, and efficacy of TERN-701 in patients with previously treated CML. Part 1 is the dose escalation portion of the trial evaluating once-daily TERN-701 monotherapy in up to five dose cohorts in up to 60 adults with chronic phase CML with confirmed BCR-ABL and a history of treatment failure or suboptimal response to at least one second generation TKI (nilotinib, dasatinib or bosutinib). Participants who are intolerant to prior TKI treatment (including asciminib) are also allowed. The primary endpoints for Part 1 are the incidence of DLTs during the first treatment cycle, and additional measures of safety and tolerability. Secondary endpoints include TERN-701 PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels. The starting dose is 160 mg once-daily (QD) with dose escalations as high as 500 mg QD and the option to explore a lower dose of 80 mg QD.
Part 2 is the dose expansion portion of the trial that 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. The primary endpoint of the dose expansion portion of the trial is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK. The overall objective of the CARDINAL trial is to select the optimal dose(s) of TERN-701 to move forward to a potential pivotal trial in chronic phase CML.
In December 2024, the company announced positive early data from the Part 1 dose escalation portion of the CARDINAL trial. As of the cutoff date in October 2024, 15 patients were enrolled across three dose levels of 160 mg (n=7), 320 mg (n=5), and 400 mg (n=3) of TERN-701 dosed once daily, with an overall median treatment duration of 3 months (range 0.79 - 7.5 months). Enrolled patients were heavily pretreated with a median of 4 prior TKIs (range: 1 - 6) and 80% having had 3 or more TKIs. 47% and 40% of patients, respectively, had previously received ponatinib and asciminib. 73% were not in MMR at baseline, with 60% having a baseline BCR-ABL transcript >1% international scale. As of the data cutoff, 14 of 15 patients remain on treatment.
12 patients were efficacy evaluable, defined as having baseline BCR-ABL transcript and at least two post-baseline BCR-ABL transcript levels (centrally assessed). All efficacy evaluable patients were in the 160 mg and 320 mg dose levels.
The incidence of treatment emergent hematologic AEs was notably low in this heavily pre-treated population, with no Grade 3 or higher treatment-related cytopenias. There were no non-hematologic treatment-related AEs more than Grade 2 in severity. Finally, no clinically meaningful changes in liver and pancreatic enzymes, blood pressure and other vitals, or electrocardiogram were seen.
Steady state PK data, available for the 160 mg and 320 mg 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. Importantly, at 160 mg and 320 mg QD, TERN-701 achieved average free drug concentrations approximately 4-fold and 8-fold higher, respectively, than in vivo exposures where potent inhibition of the BCR-ABL signaling pathway in was seen in CML mouse tumor models, indicating robust pharmacodynamic (PD) effects at these clinical doses.
As of December 2024, the CARDINAL study enrolled 19 patients inclusive of the 500 mg cohort, with all dose escalation cohorts having enrolled at least 3 patients. The backfill dosing of new participants continues in existing cohorts of dose escalation. The study is on track to initiate dose expansion in the second quarter of 2025 with additional safety and efficacy data expected in the fourth quarter of 2025. These data are expected to include a larger cohort of patients with longer durations of treatment and a potential first look at six-month MMR data, which is an approval endpoint for CML.
Solution for GLP-1 Receptor Agonists
TERN-601 is an oral, small-molecule GLP-1 receptor agonist. Internal discovery of the company’s lead GLP-1 receptor agonist was driven by computational interaction mapping, chemical synthesis and in vitro characterization of many GLP-1 receptor agonist compounds. Through this process, the company discovered TERN-601, which is a potent GLP-1 receptor agonist partially biased towards cAMP generation over Beta-arrestin recruitment.
In September 2024, the company announced positive results from the Phase 1 trial demonstrating weight loss over 28 days up to 5.5% and favorable safety and tolerability despite rapid dose titration every three days. Importantly, TERN-601 exhibited no AE-related discontinuations, interruptions or dose reductions. The majority of GI-related AEs were mild, with no severe or serious AEs and no clinically meaningful changes in liver enzymes.
Based on the Phase 1 results, TERN-601 is well positioned to demonstrate a differentiated tolerability profile in a Phase 2, 12-week setting with slower titration compared to Phase 1. The Phase 2 titration will range between two to four weeks at each intermediate dose before achieving the target dose. The titration design features the fewest steps and lowest fold change to target dose amongst leading oral, small-molecule GLP-1R agonists in a 12-week study. The company’s slower titration intends to achieve competitive 12-week weight loss, best in class tolerability and the simplest titration amongst the oral, small-molecule class.
Clinical development of TERN-601
The Phase 1 trial of TERN-601 was a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, PKs and PDs of TERN-601 in healthy adults with obesity or who are overweight. The trial consisted of two parts.
Part 1 was a SAD study that evaluated five TERN-601 dose levels in healthy participants with a BMI of = 25 kg/m2 and < 40 kg/m2. The starting TERN-601 dose was 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts.
Part 2 was a MAD study in which obese and overweight healthy adults were enrolled in cohorts that included titration of TERN-601 administered for 28 days at doses selected based on data from Part 1. Part 2 included healthy participants with a BMI of = 27 kg/m2 to < 40 kg/m2.
The primary endpoint of the trial was to evaluate safety and tolerability of TERN-601 administered once-daily for 28 days. Secondary endpoints included PK, efficacy as measured by body weight loss following 28 days of treatment with TERN-601, and other exploratory markers.
The clinical trial results showed TERN-601 was well tolerated and demonstrated dose-dependent, statistically significant placebo-adjusted mean weight loss across all three doses evaluated in the 28-day MAD study, with maximum placebo-adjusted mean weight loss of 4.9% (p<0.0001) at the highest dose of 740 mg QD.
TERN-601 was well tolerated with no treatment-related dose interruptions, reductions or discontinuations at any dose, despite fast titration to high doses. The majority (>95%) of treatment emergent AEs were mild. All gastrointestinal events were mild to moderate and consistent with the GLP-1R agonist class. Importantly, there were no clinically meaningful changes in liver enzymes, vital signs or electrocardiograms observed. The absence of treatment-related dose interruptions, reductions, or discontinuations with mostly mild AEs, despite aggressive titration to high doses in this 28-day study, indicates potential for further improved tolerability in subsequent studies with slower titration.
TERN-601 has distinct properties that may be advantageous for an oral GLP-1R agonist. Its low solubility and high gut permeability may result in prolonged absorption allowing for sustained target coverage and a flat PK curve, while high drug levels in the gut wall may lead to robust GLP-1R activation in the gut triggering satiety centers in the brain. Additionally, TERN-601 has a low free fraction in circulation which, combined with the flat PK curve, may be allowing TERN-601 to be well tolerated when administered at high doses.
The Phase 2 FALCON trial of TERN-601 initiated with the first patient enrolled in March 2025. FALCON is a U.S.-based, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of TERN-601 dosed once-daily. The trial will evaluate adults with obesity or who are overweight, without diabetes, with BMI ranges from =30 to <50 kg/m2 or =27 to <30 kg/m2 with at least one weight-related comorbidity. Patients will be randomized to one of four active cohorts (n=30 per cohort): 250 mg, 500 mg, 500 mg slow titration, 750 mg or placebo. The primary endpoint is percent change from baseline in body weight compared to placebo over 12 weeks. Secondary endpoints include safety, tolerability and proportion of patients achieving 5% weight loss or greater. Phase 2 12-week data are expected in the fourth quarter of 2025. TERN-601 has potential to be a differentiated oral, small molecule GLP-1R agonist, with competitive weight loss and superior tolerability profile in the context of a 12-week study.
TERN-501 – A Selective THR-Beta Agonist With Enhanced Metabolic Stability and Liver Distribution
THR-Beta Overview
TERN-501 is a selective THR-Beta agonist with enhanced metabolic stability and liver distribution, characteristics that are intended to improve safety and efficacy when compared to other THR-Beta candidates. THR-Beta is the major form of thyroid hormone receptor in the liver and regulates key aspects of energy metabolism, including fatty acid and lipid synthesis and removal of liver fat through induction of fatty acid oxidation. Agonism of THR-Beta increases fatty acid metabolism via mitochondrial oxidation and affects cholesterol synthesis and metabolism. As a result, THR-Beta stimulation has the potential to provide broad metabolic benefits including reducing hepatic steatosis, increasing fat oxidation, and improving fibrosis and serum lipid parameters, such as LDL cholesterol and triglycerides. THR-Beta stimulation has been identified as a target for MASH based on its potential to reduce hepatic steatosis, improve fibrosis and improve serum lipid parameters in MASH patients. For any THR agonist, a key concern is toxicity from excess systemic THR-a stimulation. TERN-501 is 23-fold more selective for THR-Beta than for THR-a activation, thereby minimizing the risk of cardiotoxicity through THR-a stimulation. TERN-501 also has high metabolic stability and a low projected clinical dose, which makes it an attractive candidate for fixed-dose combination co-formulations.
Clinical development of TERN-501
Since announcing positive top-line data from the Phase 2a DUET trial in August 2023, the company decided to limit spend in the development of TERN-501 for MASH given the current regulatory and clinical development requirements for the indication. The company continues to evaluate opportunities for TERN-501 in other metabolic diseases.
Non-clinical data suggests that TERN-501 may augment the weight loss effects of a GLP-1 receptor agonist. In 2023, the company initiated a study of TERN-501 with a GLP-1 receptor agonist, semaglutide, in a diet induced obese mouse model. In this non-clinical model, mice were fed a high calorie diet to induce overweight and obesity. Study arms included lean mouse, vehicle control, TERN-501 monotherapy, semaglutide monotherapy and semaglutide co-administered with TERN-501. Following 10 weeks of treatment, the company observed that while semaglutide alone achieved weight loss greater than 20%, semaglutide in combination with high dose TERN-501 significantly enhanced the body weight loss of semaglutide alone, achieving weight loss greater than 30%.
Based on these non-clinical data, THR-Beta agonism is a complementary mechanism to GLP-1 receptor antagonism, potentially providing broader metabolic and liver benefits in addition to increased weight loss. These preclinical combination data support the potential for TERN-501 as a combination partner for injectable and oral GLP-1 agonists for use in obesity and other metabolic disorders.
TERN-800 series – Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Modulators
GIPR Overview
GIP is secreted in response to nutrient ingestion to enhance meal-stimulated insulin secretion in a glucose-dependent manner by activating its cognate GIPR in pancreatic beta cells and other cells in various tissues. In preclinical studies, GIPR activation appears to reduce food intake and promote weight loss when combined with its incretin partner GLP-1. The overlapping body weight-lowering actions of both GIP and GLP-1 suggests that combining the actions of these two peptide hormones may bolster glucose-lowering and appetite-suppressing effects beyond those observed with individual agents.
Non-Clinical development of the TERN-800 series
As part of the company’s ongoing discovery efforts for the treatment of obesity, the company is engaging in discovery for its lead series of GIPR modulators in order to identify a development candidate. The company plans to combine oral small molecule GIPR modulators with oral small molecule GLP-1 receptor agonists, such as TERN-601, for the treatment of obesity and metabolic diseases.
The company is prioritizing its discovery efforts on nominating a GIPR antagonist development candidate based on in-house discoveries and growing scientific rationale supporting the potential of GLP-1 agonist/GIPR antagonist combinations as treatments for obesity.
Sales and Marketing
The company intends to establish a targeted commercial infrastructure in key geographies at the appropriate time prior to regulatory approval of the company’s drug therapies. The company expects to manage sales, marketing and distribution through internal resources and third-party relationships.
In addition, the company will opportunistically explore commercialization partnerships in territories outside the United States. As the company’s drug candidates progress through the company’s pipeline, its commercial plans may change. Clinical data, the size of the development programs, the size of the company’s target markets, the size of a commercial infrastructure and manufacturing needs may all influence the company’s commercialization strategies.
Intellectual Property
As of February 16, 2025, the company’s owned and exclusively licensed patent portfolio included:
For TERN-701, the company’s small-molecule allosteric inhibitor of the BCR-ABL myristoyl pocket, the company owns one patent family directed to composition-of-matter coverage of TERN-701, methods of synthesis of TERN-701, and its methods of use in the treatment of leukemia and other diseases and conditions. The patent family includes two issued U.S. patents, issued ex-U.S. patents in Australia, China, India, Chile, Colombia, Japan, Mexico, Singapore, South Africa, and Russia, and 23 allowed or pending patent applications in foreign jurisdictions, including Australia, Brazil, Canada, China, the EPO, India, Japan and Korea. Any patents that may issue from applications in the patent family are generally projected to expire in 2039, not including any patent term adjustments and any patent term extensions that may be available. This patent family is subject to an exclusive option and license agreement for the greater China region with Hansoh. For more information regarding this exclusive option and license agreement with Hansoh, please see ‘—Licensing and Other Intellectual Property-Related Agreements.’ The company also own three patent families which are collectively directed to methods of use of TERN-701 (including combination therapy) in the treatment of leukemia and other diseases and conditions. Any patents resulting from these patent families are projected to expire between 2044 and 2045, not including any patent term adjustments and any patent term extensions that may be available.
For TERN-501, the company’s THR-Beta agonist, the company own six patent families which collectively are directed to composition-of-matter coverage of TERN-501 and its methods of use (including combination therapy) in the treatment of obesity and certain liver, metabolic and other diseases and conditions. The composition-of-matter patent family includes two issued U.S. patents, issued ex-U.S. patents in China, Chile, Colombia, Israel, India, Japan, Macau, Mexico, Hong Kong, Taiwan, and Russia, three pending U.S. applications, and over 25 pending applications (including allowed applications) in foreign jurisdictions, including Australia, Brazil, Canada, China, the EPO, India, Japan and Korea. Any patents that may issue from applications in the composition-of-matter patent family are generally projected to expire in 2039 except patents, which may issue from the pending Chinese priority application are projected to expire in 2038, not including any patent term adjustments and any patent term extensions that may be available.
The company owns twelve patent families covering a number of GLP-1R agonists, including TERN-601. These patent families collectively are directed to composition of matter coverage for TERN-601 and other small molecule GLP-1R agonists, as well as formulations and method of use thereof (including combination therapy) in the treatment of obesity and certain metabolic diseases. Any patents that may issue from applications in these patent families are generally projected to expire between 2041 and 2045, not including any patent term adjustments and any patent term extensions that may be available.
The company owns a patent family directed to small molecule GIPR modulators. Any patents that may issue from this patent family are projected to expire in 2045, not including any patent term adjustments and any patent term extensions that may be available.
Licensing and Other Intellectual Property-Related Agreements
TERN-701 Exclusive Option and License Agreement with Hansoh
In July 2020, the company entered into an exclusive option and license agreement with Hansoh pursuant to which the company granted an exclusive option to Hansoh to obtain an exclusive, sub-licensable and royalty-bearing license under certain patent and other intellectual property rights owned or controlled by the company, including patents claiming the composition of TERN-701, the company’s small-molecule allosteric inhibitor of the BCR-ABL fusion gene and methods of using the same, to research, develop, manufacture, use, distribute, sell and otherwise exploit therapeutic products containing TERN-701, or Hansoh Products, for all prophylactic, palliative, therapeutic and/or diagnostic uses in human diseases and disorders in the field of oncology in mainland China, Taiwan, Hong Kong and Macau, or the Hansoh Territory. In November 2021, Hansoh exercised its option to in-license TERN-701 in accordance with the terms of the exclusive option and license agreement. The company retains co-exclusive rights under certain know-how licensed to Hansoh and all rights under the patent rights outside of the field of oncology and Hansoh Territory. Pursuant to the terms of the option and license agreement, Hansoh must use commercially reasonable efforts to develop and commercialize a Hansoh Product in the Hansoh Territory and Hansoh may not exploit any other product in the Hansoh Territory with the same primary mechanism of action as the Hansoh Products.
THR-Beta Agonist Assignment Agreement with Vintagence Biotechnology Ltd.
In June 2019, the company entered into an assignment agreement with Vintagence Biotechnology Ltd., or Vintagence, pursuant to which Vintagence assigned to the company certain worldwide intellectual property rights and know-how directed to THR-Beta agonists. In particular, the company has been assigned all rights, title and interest in and to a Chinese patent application and any patents or patent applications resulting or derived therefrom in any country, know-how and potentially certain other patents or patent applications relating to the company’s THR-Beta program. The company is also entitled to license the rights granted to the company under the assignment agreement to the company’s affiliates, licensees or contractors. The company will be responsible for all regulatory activities, including the obtaining of regulatory approvals for a product.
The company must use commercially reasonable efforts to develop and commercialize a product based on the assigned intellectual property in each of several major market territories.
Government Regulation and Product Approval
Among others, the FDA, the European Commission, U.S. Department of Health and Human Services Office of Inspector General, the Centers for Medicare and Medicaid Services, or CMS, and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements on companies involved in the clinical development, manufacture, marketing and distribution of drugs such as those the company is developing. These agencies and other federal, state and local entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling and export and import of the company’s product candidates. Any drug candidates that the company develops must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in those foreign countries.
History
Terns Pharmaceuticals, Inc. was founded in 2016. The company was incorporated in 2016.
