OUR PROGRAMS

TERN-701 is Terns’ proprietary, oral, potent, allosteric BCR-ABL TKI, designed to target the ABL myristoyl pocket, which is in development for the treatment of chronic myeloid leukemia (CML), a form of cancer that begins in the bone marrow

• CML is a chronic, orphan indication with a need for multiple agents, driven by lifelong treatment and frequent switching of therapies

• A recently approved allosteric BCR-ABL TKI has demonstrated significant (~2x) efficacy improvement compared to second generation standard-of-care active site inhibitors

TERN-701 is licensed to Hansoh Pharmaceutical Group Company Limited for development in the greater China region (referred to as HS-10382 by Hansoh); Terns retains all worldwide development and commercialization rights outside of greater China, as well as access to data generated by Hansoh in China

• Hansoh’s Phase 1 trial of TERN-701 in CML patients in China is ongoing; Hansoh is responsible for all development and commercialization-related activities in greater China

In October 2023, Terns initiated the Phase 1 CARDINAL trial of TERN-701 in the U.S. 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 relapsed/refractory CML

In March 2024, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TERN-701 for the treatment of CML

In April 2024, Terns announced findings from a concurrent Phase 1 PK study of TERN-701 in U.S. healthy volunteers, which indicated TERN-701 can be administered once-daily with or without food at doses that achieve clinically efficacious exposures

In December 2024, Terns announced positive early data from the Phase 1 CARDINAL trial of TERN-701 in patients with relapsed/refractory CML. With a data cutoff date of October 28, 2024, TERN-701 demonstrated:

• Compelling molecular responses starting at lowest dose level in heavily pre-treated patients with high baseline BCR-ABL transcript levels

• Encouraging safety profile with no dose limiting toxicities, adverse event-related treatment discontinuations, or dose reductions across three dose escalation cohorts

• High levels of target coverage achieved with once daily dosing at all doses
  

TERN-601 is an oral small-molecule glucagon-like peptide-1 receptor, or GLP-1R, agonist in development for the treatment of obesity

Terns has identified structures believed to be suitable for oral administration as a single-agent or in combination with other drug candidates within its pipeline

In September 2024, Terns announced positive top-line data from the Phase 1 clinical trial of TERN-601, the company’s lead GLP-1R development candidate, in healthy adults who have obesity or are overweight

• Treatment with TERN-601 demonstrated statistically significant, dose-dependent placebo-adjusted mean weight loss over 28 days with once-daily dosing

• TERN-601 was well tolerated with no treatment-related dose interruptions, reductions, or discontinuations even with rapid dose titration

• Distinct drug properties enabled sustained target coverage and a flat pharmacokinetic curve, and may lead to a differentiated clinical profile in subsequent studies

• Results support the potential of TERN-601 as a leading GLP-1R agonist with promising efficacy, tolerability and manufacturing scalability

• Terns plans to initiate a Phase 2 clinical trial in 2025

TERN-501 is a thyroid hormone receptor beta (THR-β) agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development

• Research shows other THR-β agonists face limitations with off-target effects, unpredictable PK, or need for cytochrome P450 (CYP) metabolism

Preclinical studies have demonstrated that TERN-501 is 23-fold more selective for THR-β than for THR-α activation thereby minimizing the risk of cardiotoxicity and other off-target effects associated with non-selective THR stimulation. 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

In November 2023, Terns presented top-line data from the Phase 2a DUET trial of TERN-501 in a late-breaking oral presentation at AASLD’s The Liver Meeting

• Phase 2a DUET trial achieved all primary and secondary efficacy endpoints with a differentiated safety profile

In June 2024, Terns presented new preclinical data at the American Diabetes Association (ADA) 84th Scientific Sessions supporting TERN-501 in combination with a GLP-1 receptor agonist for the treatment of obesity

• Preclinical findings demonstrated TERN-501 in combination with semaglutide significantly enhanced weight loss and showed proportionally greater loss of fat mass relative to lean mass compared to semaglutide alone

• Results 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

Terns is combining internal chemistry expertise with external synthesis teams to develop initial set of 800 series compounds based on improving known scaffolds

Discovery efforts are ongoing for small molecule GIPR modulators for obesity, which have the potential for combination with GLP-1 receptor agonists

• In prior research GIPR modulators have shown high potential in weight loss (about 15%-20% mean weight loss)

Terns 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 receptor agonist/GIPR antagonist combinations for obesity