Lexicon Pharmaceuticals Announces Publication of Preclinical Data in the Journal of the Endocrine Society on Acyl-CoA Synthetase 5 (ACSL5) Reinforcing the Scientific Rationale for LX9851

Rhea-AI Summary

Lexicon Pharmaceuticals (Nasdaq: LXRX) announced publication of preclinical data on ACSL5 in the Journal of the Endocrine Society on Dec 10, 2025, reinforcing the rationale for its oral ACSL5 inhibitor LX9851. Animal studies showed ACSL5 knockout mice and mice given potent oral ACSL5 inhibitors had lower body weight and body fat, reduced triglycerides, total cholesterol and blood glucose, and preserved lean mass versus controls.

Mechanistic work linked effects to activation of the ileal brake, which delayed gastric emptying and reduced food intake. Lexicon holds an exclusive worldwide license for LX9851 with Novo Nordisk (March 2025).

Positive

• Exclusive worldwide license for LX9851 with Novo Nordisk (March 2025)
• Oral ACSL5 inhibitors reduced body weight and body fat in diet-induced obese mice
• Preclinical results show lower triglycerides, total cholesterol and blood glucose in mice
• Mechanism identified: ileal brake activation causing delayed gastric emptying and reduced intake

Negative

• Findings are preclinical and limited to mouse models; no human efficacy data reported
• No clinical trial results, dosing, safety, or timelines disclosed for LX9851

News Market Reaction – LXRX

+0.76%

2 alerts

+0.76% News Effect

+$4M Valuation Impact

$476M Market Cap

2K Volume

On the day this news was published, LXRX gained 0.76%, reflecting a mild positive market reaction. Our momentum scanner triggered 2 alerts that day, indicating moderate trading interest and price volatility. This price movement added approximately $4M to the company's valuation, bringing the market cap to $476M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Q3 2025 revenue: $14.2M Q3 net loss: $12.8M Cash & investments: $145.0M +5 more

8 metrics

Q3 2025 revenue $14.2M Q3 2025 total revenue, largely Novo Nordisk licensing

Q3 net loss $12.8M Q3 2025 net loss, improved vs prior year

Cash & investments $145.0M Balance as of Sept 30, 2025 including restricted cash

ATM capacity $75,000,000 Maximum size of at-the-market equity program

Novo upfront $45M Upfront payment from Novo Nordisk for LX9851 license

Novo total potential $1B Total potential payments under Novo Nordisk LX9851 deal

INPEFA revenue $1.0M Net product revenue from INPEFA in Q3 2025

Long-term debt $56.5M Long-term debt carrying value after $45M repayment

Market Reality Check

Price: $1.47 Vol: Volume 1,995,918 vs 20-da...

normal vol

$1.47 Last Close

Volume Volume 1,995,918 vs 20-day average 1,766,066 (relative 1.13x), indicating elevated trading interest pre‑news. normal

Technical Shares traded above the 200-day MA, at $1.31 vs $0.96, while sitting 21.08% below the 52-week high.

Peers on Argus

LXRX was down 5.76% with slightly elevated volume, while peers showed mixed move...

1 Down

LXRX was down 5.76% with slightly elevated volume, while peers showed mixed moves: FULC +14.78%, SLDB +1.41%, ATXS +0.08%, AURA -0.31%, INBX -4.33%. Momentum scanner only flagged FULC moving down later, reinforcing a stock‑specific setup for LXRX ahead of this preclinical update.

Historical Context

5 past events · Latest: Dec 05 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 05	Clinical data update	Positive	-1.4%	Upcoming HFpEF adipose distribution data presentation at CVCT 2025.
Nov 25	Investor conferences	Neutral	-0.7%	Participation in two December 2025 healthcare investor conferences.
Nov 11	Investor conference	Neutral	+9.9%	Jefferies London Healthcare Conference fireside chat announcement.
Nov 06	Earnings and pipeline	Positive	+3.6%	Q3 2025 results plus multiple pipeline and licensing updates.
Nov 04	Clinical data presentations	Positive	-2.2%	Planned sotagliflozin presentations at HCM and AHA 2025 sessions.

Pattern Detected

Investor reactions to LXRX news have been mixed: strong gains on some conference and earnings updates, but several scientific or presentation‑focused releases saw mild to moderate declines, indicating no consistent pattern of buying on positive R&D headlines.

Recent Company History

Over the last few months, Lexicon reported Q3 2025 results with $14.2M revenue and a narrowed net loss of $12.8M, supported by the Novo Nordisk licensing deal and INPEFA sales. The company highlighted multiple sotagliflozin data presentations at major cardiology meetings in November 2025, plus additional HFpEF adipose distribution data scheduled for CVCT on Dec 8, 2025. Conference and data‑related news produced both gains and pullbacks, so today’s preclinical LX9851 publication fits into an ongoing R&D‑driven narrative with variable short‑term price responses.

Market Pulse Summary

This announcement highlights preclinical data supporting ACSL5 inhibition and the rationale for LX98...

Analysis

This announcement highlights preclinical data supporting ACSL5 inhibition and the rationale for LX9851, now licensed to Novo Nordisk following a $45M upfront payment and up to $1B in potential milestones. In animal models, ACSL5 knockout or inhibition improved body fat and metabolic markers, reinforcing its relevance in obesity. In context of Q3 2025 revenue of $14.2M and cash of $145.0M, investors may track progress toward clinical studies, regulatory milestones, and future data readouts for LX9851.

Key Terms

acyl-coa synthetase 5, acsl5, ileal brake, triglycerides, +2 more

6 terms

acyl-coa synthetase 5 medical

"publication of preclinical data validating Acyl-CoA Synthetase 5 (ACSL5) as a target"

Acyl‑CoA synthetase 5 is a cellular enzyme that helps convert free fatty acids into a form the body can use or store by attaching a small helper molecule (coenzyme A), much like putting a shipping label on a package so it can be routed for processing. It matters to investors because changes in its activity are linked to metabolic health, inflammation and some cancers, making it a potential drug target or biomarker that can affect the value of companies developing therapies or diagnostics.

acsl5 medical

"ACSL5 is an enzyme encoded by the Acsl5 gene that plays a vital role"

ACSL5 is a human gene that makes an enzyme responsible for activating long-chain fatty acids so cells can use or store them; think of it as a factory worker that tags raw fat molecules so they can be processed. Investors should care because changes in ACSL5 activity are linked to metabolic diseases, cancer and drug responses, making it a potential diagnostic marker or drug target that can influence the value of related biotech and pharma projects.

ileal brake medical

"protect against diet-induced obesity in mice by activating the ileal brake"

The ileal brake is a natural gut feedback mechanism where the presence of undigested food, especially fats, in the last part of the small intestine triggers signals that slow stomach emptying and intestinal movement. For investors, it matters because medical treatments, weight-loss therapies, and certain drugs or devices that alter this feedback can change appetite, nutrient absorption and drug effectiveness—think of it as a built-in slow-down switch that companies try to modulate.

triglycerides medical

"had lower body fat, triglycerides, total cholesterol, and blood glucose"

Triglycerides are the main form of fat carried in the bloodstream, made from excess calories and used by the body for energy or stored in fat tissue; think of them as the oil reserves that fuel the body. They matter to investors because high or low levels influence demand for drugs, diagnostics, and healthcare services, affect regulatory reviews and insurance costs, and signal population health trends that can change market size and company risk.

gastric emptying medical

"ileal brake mechanism which delayed gastric emptying and decreased food consumption"

Gastric emptying is the speed at which food or liquid moves out of the stomach into the small intestine. Investors should care because this process influences how quickly and how much of an oral drug is absorbed, affects treatments for digestive, metabolic and weight-related conditions, and can change a medicine’s effectiveness, dosing and market potential — like regulating the flow from a reservoir to a downstream channel.

knockout medical

"Acyl-CoA Synthetase 5 knockout and inhibitors protect against diet-induced obesity"

A knockout is a type of option that automatically ends and becomes worthless if the underlying stock or index crosses a predetermined price level called the barrier. Think of it like a discount coupon that vanishes if the price moves past a marked line: it typically costs less than a regular option and can amplify returns, but it also means the investor can lose the entire premium if the barrier is hit, affecting risk, pricing and strategy.

AI-generated analysis. Not financial advice.

THE WOODLANDS, Texas, Dec. 10, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced the publication of preclinical data validating Acyl-CoA Synthetase 5 (ACSL5) as a target for obesity and chronic weight management. The paper, titled “Acyl-CoA Synthetase 5 knockout and inhibitors protect against diet-induced obesity in mice by activating the ileal brake,” was published online in the Journal of the Endocrine Society.

ACSL5 is an enzyme encoded by the Acsl5 gene that plays a vital role in lipid metabolism and is the target of LX9851, the Company’s investigational non-incretin, oral, small molecule ACSL5 inhibitor. Animal model data showed that mice genetically modified to lack the ACSL5 gene exhibited favorable metabolic characteristics, including reduced body fat and conserved lean body mass.

In March 2025, Lexicon entered into an exclusive, worldwide licensing agreement for LX9851 with Novo Nordisk.

“These preclinical findings validate our strategy of targeting ACSL5 for the development of new therapeutic options for people in need of obesity and weight management treatment and support the clinical advancement of LX9851,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “We see an opportunity for LX9851 to build on the success of incretin-based therapies as the obesity treatment landscape continues to evolve. With a novel mechanism, oral administration, strong preclinical results and possibility for both monotherapy and combination applications, we feel LX9851 has the potential to occupy a unique space in the treatment landscape for obesity and metabolic conditions. We look forward to continuing the work with Novo Nordisk to maximize the potential of this innovative medicine.”

Preclinical Research Findings
Lexicon scientists generated mice with the ACSL5 gene deleted (knocked out) globally. These ACSL5 knockout mice had lower body fat, triglycerides, total cholesterol, and blood glucose as well as conserved lean body mass compared with mice carrying the ACSL5 gene. Additionally, ACSL5 knockout mice had lower body weight and body fat while maintaining their lean body mass when fed a high-fat diet. Similar effects were also observed when potent, small molecule inhibitors of ACSL5 were administered orally to mice with diet-induced obesity. Mechanistic studies demonstrated that the favorable metabolic characteristics observed were by activating the ileal brake mechanism which delayed gastric emptying and decreased food consumption.

About LX9851
LX9851 is a first-in-class, non-incretin, oral, small molecule inhibitor of acyl-CoA synthetase 5 (ACSL5) for the treatment of obesity and associated cardiometabolic disorders. Lexicon scientists identified the function of ACSL5, the target of LX9851, based on their discovery that knockout mice lacking the target enzyme exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition. Lexicon has investigated the pharmacology of LX9851 as a stand-alone therapy and in combination with GLP-1 agonists such as semaglutide.

About Lexicon Pharmaceuticals    
Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in discovery and clinical and preclinical development in heart failure, neuropathic pain, obesity, cardiology, diabetes and other indications. For additional information, please visit www.lexpharma.com.

Safe Harbor Statement  
This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of LX9851 and its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2024, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

For Investor and Media Inquiries:
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com

FAQ

What did Lexicon announce about ACSL5 and LX9851 on Dec 10, 2025 for LXRX?

Publication of preclinical data showing ACSL5 knockout and oral ACSL5 inhibitors reduced body weight, body fat and metabolic markers in mice, supporting LX9851.

How do ACSL5 inhibitors like LX9851 work according to the Dec 2025 publication?

Mechanistic studies linked ACSL5 inhibition to activation of the ileal brake, which delayed gastric emptying and lowered food intake in mice.

Does the Dec 10, 2025 announcement report human clinical results for LX9851 (LXRX)?

No; the announcement describes preclinical mouse data only and does not report human clinical trial results.

When did Lexicon license LX9851 to Novo Nordisk and is it exclusive for LXRX?

Lexicon entered an exclusive, worldwide licensing agreement for LX9851 with Novo Nordisk in March 2025.

What metabolic markers improved in mice treated with ACSL5 inhibitors in the Dec 2025 study?

Treated mice showed lower body fat, triglycerides, total cholesterol and blood glucose while preserving lean mass.