Terns Pharmaceuticals Announces Positive Phase 1 Clinical Trial Results with TERN-601 Once-Daily Oral GLP-1R Agonist for the Treatment of Obesity

Rhea-AI Summary

Terns Pharmaceuticals (Nasdaq: TERN) announced positive Phase 1 clinical trial results for TERN-601, its once-daily oral GLP-1R agonist for obesity treatment. The trial showed:

- Statistically significant mean weight loss up to 5.5% over 28 days (4.9% placebo-adjusted)
- Well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations
- Maximum placebo-adjusted mean weight loss of 4.9% (p<0.0001) at the highest dose of 740 mg QD
- 67% of participants lost 5% or more of baseline body weight at the top dose

The company plans to initiate a Phase 2 clinical trial in 2025. TERN-601's distinct properties support its potential to be a leading GLP-1R agonist, with possible applications as monotherapy or in combination with other agents.

Positive

• Statistically significant mean weight loss up to 5.5% over 28 days (4.9% placebo-adjusted)
• Well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations
• 67% of participants lost 5% or more of baseline body weight at the top dose
• Potential for improved tolerability in future studies with slower titration
• Distinct drug properties supporting potential as a leading GLP-1R agonist
• Plans to initiate Phase 2 clinical trial in 2025

Negative

• None.

Clinical Research Analyst

The Phase 1 results for TERN-601 are highly promising. A 4.9% placebo-adjusted mean weight loss over just 28 days is impressive, especially considering the 67% of participants who lost ≥5% of their baseline weight at the highest dose. This efficacy is comparable to, if not better than, some existing GLP-1R agonists in early-stage trials.

The tolerability profile is particularly noteworthy. No treatment-related dose interruptions, reductions, or discontinuations even with rapid dose titration is exceptional for this drug class. This suggests potential for improved patient adherence and possibly faster dose escalation in clinical practice.

The distinct pharmacokinetic properties of TERN-601, including low solubility and high gut permeability, may contribute to its favorable efficacy and safety profile. This could differentiate it from other oral GLP-1R agonists in development.

Financial Analyst

Terns Pharmaceuticals' announcement is a significant positive for the company. The obesity market is currently valued at over $100 billion and growing rapidly. With TERN-601 showing promising efficacy and tolerability, Terns could capture a substantial market share if these results translate to later-stage trials.

The company's plan to initiate Phase 2 trials in 2025 suggests a clear development pathway. However, investors should note that significant capital will be required to fund these trials. Terns may need to raise additional funds, potentially diluting current shareholders.

The potential for combination therapy with TERN-501 (THR-β agonist) or TERN-800 series (GIPR modulator) could provide multiple shots on goal and diversify risk. This multi-pronged approach could enhance Terns' value proposition to potential partners or acquirers in the highly competitive obesity drug market.

Pharmaceutical Industry Expert

TERN-601's Phase 1 results position it as a strong contender in the increasingly crowded GLP-1R agonist space. The once-daily oral dosing is a key advantage over injectable options, potentially improving patient compliance and expanding the addressable market.

The drug's unique properties allowing for high dosing with good tolerability could be a game-changer. This may enable higher efficacy without compromising safety, addressing a critical need in obesity treatment.

However, the road ahead is long and challenging. Phase 2 and 3 trials will need to demonstrate sustained efficacy and safety over longer periods. Additionally, Terns will face stiff competition from established players like Novo Nordisk and Eli Lilly, who are already marketing successful GLP-1R agonists. Terns' ability to differentiate TERN-601 and navigate the regulatory landscape will be important for its success in this high-stakes market.

Statistically significant mean weight loss up to 5.5% over 28 days (4.9% placebo adjusted)

Well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations even with rapid dose titration

Distinct drug properties support potential to be a leading GLP-1R agonist

Plans to initiate Phase 2 clinical trial in 2025

Company to host conference call today at 8:00 am ET

FOSTER CITY, Calif., Sept. 09, 2024 (GLOBE NEWSWIRE) -- 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, today announced positive top-line data from its Phase 1 randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TERN-601 dosed once-daily (QD) in healthy adults with obesity or overweight.

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. Additionally, 67% of participants lost 5% or more of their baseline body weight at the top dose.

“These compelling results underscore TERN-601’s potential to be a class-leading GLP-1R agonist based on its composite profile of initial indications of efficacy, tolerability and manufacturing scalability,” said Amy Burroughs, chief executive officer of Terns. “These data validate the potential of TERN-601 for the treatment of obesity as monotherapy or in combination with agents such as TERN-501, our internally discovered, clinical stage THR-β agonist, or a GIPR modulator from our TERN-800 series. With operational preparations well underway, we look forward to swiftly advancing this promising product candidate into Phase 2 clinical development in 2025.”

“We are delighted to demonstrate potent GLP-1R agonism with TERN-601 as its distinct drug properties allowed for sustained target coverage with once-daily dosing and the evaluation of doses up to 740 mg, while being tolerable,” noted Emil Kuriakose, chief medical officer of Terns. “Importantly, we believe we have successfully identified an optimal range of clinically active, well tolerated doses to take forward in Phase 2 clinical trials, with no new dose range exploration anticipated.”

Table 1: Mean Percent Weight Change from Baseline to Day 28

	Placebo (N=9)	TERN-601 240 mg (N=9)	TERN-601 500 mg (N=9)	TERN-601 740 mg (N=9)
% weight change from baseline	-0.6%	-2.5%	-4.4%	-5.5%
% weight change placebo-adjusted (90% CI)	-	-1.9%	-3.8%	-4.9%
Exploratory p-value vs. placebo	-	<0.1	<0.01	<0.0001

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.

Table 2: Treatment Emergent Adverse Events by Maximum Severity

	Placebo (N=9)	TERN-601 240 mg (N=10)	TERN-601 500 mg (N=9)	TERN-601 740 mg (N=9)
Grade 1 (Mild)	5 (55.6%)	5 (50%)	9 (100%)	3 (33.3%)
Grade 2 (Moderate)	0	1 (10%)	0	6 (66.7%)
Grade ≥3 (Severe)	0	0	0	0
Serious Adverse Events	0	0	0	0

Terns plans to submit data from this informative clinical trial for presentation at an upcoming scientific conference.

Conference Call and Webcast
Terns will host a conference call for investors today, September 9, 2024, beginning at 8:00 a.m. ET. The live webcast of the conference call can be accessed here. A replay of the call will also be available on the Events page of the Investor Relations section of the Terns website for 30 days.

About the TERN-601 Phase 1 Trial
The Phase 1 trial was a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or overweight. The trial consisted of two parts.

Part 1 (SAD) was a single ascending dose study that evaluated five TERN-601 dose levels in healthy participants with a Body Mass Index (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.

In Part 2 (MAD) of the trial, 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 (SAD). 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.

About TERN-601
TERN-601 is an oral, small-molecule glucagon-like peptide-1 receptor agonist, or GLP-1R agonist, internally discovered at Terns for development in obesity. TERN-601 was designed through internal structure-based drug discovery efforts employing Terns’ proprietary three-dimensional QSAR model of the receptor. The ligands were further optimized based on in vitro activity, metabolic stability, and pharmacokinetic parameters. This process led to the selection of TERN-601, a potent GLP-1R agonist biased towards cAMP generation.

About Terns Pharmaceuticals
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. Terns’ pipeline contains three clinical stage development programs including an allosteric BCR-ABL inhibitor, a small-molecule GLP-1 receptor agonist, a THR-β agonist, and a preclinical GIPR modulator discovery effort, prioritizing a GIPR antagonist nomination candidate. For more information, please visit: www.ternspharma.com.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about Terns Pharmaceuticals, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including those related to expectations, timing and potential results of the clinical trials and other development activities of the Company and its partners; the potential indications to be targeted by the Company with its small-molecule product candidates; the therapeutic potential of the Company’s small-molecule product candidates; the potential for the mechanisms of action of the Company’s product candidates to be therapeutic targets for their targeted indications; the potential utility and progress of the Company’s product candidates in their targeted indications, including the clinical utility of the data from and the endpoints used in the Company’s clinical trials; the Company’s clinical development plans and activities, including the results of any interactions with regulatory authorities on its programs; the Company’s expectations regarding the profile of its product candidates, including efficacy, tolerability, safety, metabolic stability and pharmacokinetic profile and potential differentiation as compared to other products or product candidates; the Company’s plans for and ability to continue to execute on its current development strategy, including potential combinations involving multiple product candidates; the Company’s plans and expectations around the addition of key personnel; and the Company’s expectations with regard to its cash runway and sufficiency of its cash resources. All statements other than statements of historical facts contained in this press release, including statements regarding the Company’s strategy, future financial condition, future operations, future trial results, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results and the implementation of the Company’s plans to vary materially, including the risks associated with the initiation, cost, timing, progress, results and utility of the Company’s current and future research and development activities and preclinical studies and clinical trials. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s SEC reports, including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2023. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.

Contacts for Terns

Investors
Justin Ng
investors@ternspharma.com

Media
Jenna Urban
Berry & Company Public Relations
media@ternspharma.com

FAQ

What were the main results of Terns Pharmaceuticals' Phase 1 trial for TERN-601?

The Phase 1 trial of TERN-601 showed statistically significant mean weight loss up to 5.5% over 28 days (4.9% placebo-adjusted). The highest dose (740 mg QD) achieved a maximum placebo-adjusted mean weight loss of 4.9% (p<0.0001), with 67% of participants losing 5% or more of their baseline body weight.

How well was TERN-601 tolerated in the Phase 1 trial?

TERN-601 was well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations at any dose, despite fast titration to high doses. Over 95% of treatment emergent adverse events were mild, and all gastrointestinal events were mild to moderate, consistent with the GLP-1R agonist class.

When does Terns Pharmaceuticals (TERN) plan to start Phase 2 trials for TERN-601?

Terns Pharmaceuticals plans to initiate Phase 2 clinical trials for TERN-601 in 2025. The company stated that operational preparations are already underway to advance this product candidate into the next phase of development.

What are the potential applications of TERN-601 based on the Phase 1 results?

Based on the Phase 1 results, TERN-601 shows potential as a treatment for obesity, either as a monotherapy or in combination with other agents. Terns Pharmaceuticals suggests it could be combined with TERN-501 (their THR-β agonist) or a GIPR modulator from their TERN-800 series.