We are rapidly executing on the development of internally discovered small molecule medicines with de-risked mechanisms of action to address oncology and metabolic diseases with large unmet medical needs.
PROGRAM | MECHANISM | INDICATION | PRECLINICAL | EARLY-STAGE CLINICAL DEVELOPMENT |
LATE-STAGE CLINICAL DEVELOPMENT |
---|---|---|---|---|---|
+ Oncology
TERN-701*
|
Allosteric BCR-ABL inhibitor |
CML |
Phase 1 |
||
+ Metabolic
TERN-601
|
Oral GLP-1R agonist |
Obesity |
Phase 2 ready |
||
+ TERN-501
Monotherapy / Combination |
THR-β agonist / THR-β agonist + metabolic agent | MASH / NASH / Obesity | Phase 2 ready | ||
+ TERN-800
series |
GIPR modulators | Obesity | GIPR antagonist lead optimization |
+
+
+
+
*In 2020, Terns granted Hansoh exclusive option to license TERN-701 in mainland China, Taiwan, Hong Kong, and Macau.
CML = chronic myeloid leukemia; GLP-1R = glucagon-like peptide-1 receptor; THR-β = thyroid hormone receptor beta; GIPR = glucose-dependent insulinotropic polypeptide receptor; MASH = metabolic dysfunction-associated steatohepatitis; NASH = nonalcoholic steatohepatitis.
At Terns, we are committed to elevating human health. We are interested in collaborators who share this vision and whose capabilities complement our best-in-class drug discovery and development team.
CONTACT USTERN-701 is a proprietary, oral, potent, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) that has been granted Orphan Drug Designation by the United States Food and Drug Administration (FDA) for the treatment of CML. It’s designed to target the ABL myristoyl pocket, a unique mechanism of action different from traditional TKIs. A recently approved allosteric BCR-ABL TKI has demonstrated significant efficacy improvements versus first and second generation standard of care active site inhibitors.1,2
Emerging data support the potential for TERN-701 as the best-in-class allosteric TKI based on three differentiation pillars
Terns is studying the safety, pharmacokinetics, and efficacy of TERN-701 in participants with relapsed/refractory CML in the Phase 1 CARDINAL trial (NCT06163430).
LEARN MORE ABOUT CARDINALChronic myeloid leukemia, or CML, is a type of cancer that develops in the bone marrow. It occurs when a genetic abnormality called the Philadelphia chromosome causes bone marrow cells to produce too many abnormal white blood cells, particularly granulocytes. As a result, the now-cancerous cell produces a protein (in the tyrosine kinase family of proteins) that encourages it to multiply rapidly. Leukemias with the Philadelphia chromosome can be treated with targeted therapies called tyrosine kinase inhibitors. These drugs interfere with the tyrosine kinase protein and therefore the multiplication of cancerous white blood cells.
TERN-601 is an oral small molecule GLP-1RA in development as a single agent or in combination with other drug candidates within our pipeline for the treatment of obesity. With unique drug properties and the potential for simplified titration, TERN-601 could potentially offer competitive weight loss and class-leading safety/tolerability profile.
TERN-601 has the potential for a differentiated product profile
Terns is studying the efficacy, safety, and tolerability of TERN-601 in adults with overweight or obesity in a Phase 2 trial (NCT06854952).
LEARN MORE ABOUT FALCONAbout obesity and the challenges of current GLP-1RA therapies
A large and growing portion of the population is overweight or obese, conditions that demand urgent attention due to their association with serious health complications. GLP-1RA therapies have been instrumental in helping people lose weight; however, poor gastrointestinal tolerability requiring long and complex titration is a key challenge for most oral GLP-1RAs. This therapeutic gap highlights the pressing need for next-generation GLP-1RA formulations that can achieve comparable efficacy while improving on current tolerability and titration challenges.
A highly selective thyroid hormone receptor-beta (THR-β) agonist for obesity
TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution, and greater selectivity for THR-β vs other THR-β agonists in development. It is 23-fold more selective for THR-β vs THR-α activation, which may minimize the risk of cardiotoxicity and other off-target effects associated with non-selective THR stimulation. Positive Phase 2a data from the DUET study in patients with nonalcoholic steatohepatitis (NASH) supports a compelling profile of efficacy, tolerability and combinability.
Preclinical data show TERN-501 + semaglutide significantly enhanced weight loss and showed proportionally greater loss of fat mass relative to lean mass vs semaglutide alone. TERN-501 has been designed to be metabolically stable and therefore is expected to have little pharmacokinetic variability and a low clinical dose, making it an attractive candidate for use in fixed-dose combinations.
THR-β agonism represents a promising therapeutic approach for treating obesity through its regulation of key energy metabolism pathways, including fatty acid and lipid synthesis as well as liver fat removal via enhanced fatty acid oxidation. The combination of GLP-1 and THR-β targeting offers significant potential for addressing multiple metabolic disorders simultaneously by engaging complementary pathways involved in weight control.
Glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist for obesity
Terns is currently prioritizing its discovery efforts on nominating a potentially class-leading small molecule GIPR antagonist development candidate. This direction is based on in-house discoveries as well as growing scientific rationale supporting the potential of GLP-1RA/GIPR antagonist combinations for obesity.
We have combined internal chemistry expertise with external synthesis teams to develop an initial set of 800 series compounds. Candidate nomination activities are ongoing.
About GIPR modulators for the treatment of obesity
GIPR modulators have shown high potential for treating obesity. These agents target the GIPR, which is thought to regulate both glucose metabolism and energy balance. By modulating GIP signaling, GIPR modulators could potentially promote satiety, reduce food intake, and enhance metabolic efficiency. Combining this approach with GLP-1RAs has demonstrated promising results in clinical trials, with this combination having the potential to be a promising new option for the treatment of obesity.
References: 1. Rea D et al. Blood. 2021;138(21):2031-2041. 2. Hochhaus A et al. N Engl J Med. 2024;391(10):885-898.