Alaunos Therapeutics Announces Positive Preclinical Proof-of-Concept Data for ALN1003, a Differentiated Non-Hormonal Oral Treatment for Obesity and Related Metabolic Disorders

Rhea-AI Summary

Alaunos Therapeutics (Nasdaq: TCRT) reported positive non-GLP preclinical DIO mouse data for ALN1003, an oral non-hormonal obesity candidate. Key findings: dose-dependent weight loss (peak -12.9% at Day 34), marked liver-weight reductions (up to -55%), improved glucose (197 vs 320 mg/dL) and lower total cholesterol.

Company plans further preclinical, CMC, formulation work, IND-enabling studies and next-generation chemistry; cash was ~$1.9M as of Sept 30, 2025, with runway into Q2 2026.

Positive

• Body weight reduction of up to -12.9% (peak at Day 34)
• Liver weight reductions up to -55.0% in high-dose mice
• Glucose lowered from 320 to 197 mg/dL in high-dose group (~-38%)
• Total cholesterol reduction of ~22% (209 to 162 mg/dL)
• Dose-dependent fat loss and favorable body composition changes

Negative

• Cash runway into Q2 2026 with only ~$1.9M on hand
• Anorexia/hypodipsia confounds attribution of weight loss to drug exposure
• High-dose lean mass and fluid losses (lean grams -18.8%, fluid grams -47.3%)
• Two high-dose mice showed dehydration during PK portion

Key Figures

Cash & equivalents: $1.9 million Net loss: $1,159 thousand Operating expenses: $1,187 thousand +5 more

8 metrics

Cash & equivalents $1.9 million As of September 30, 2025; cash runway into Q2 2026

Net loss $1,159 thousand Q3 2025 net loss from 10‑Q

Operating expenses $1,187 thousand Q3 2025 operating expenses

Cash & equivalents $1,938 thousand As of September 30, 2025 per 10‑Q

Cash runway Into Q2 2026 Company statement alongside ALN1003 update

Shelf registration size $50,000,000 Mixed shelf for primary securities on Form S‑3/A

Body weight change -12.9% Peak mean percent change vs DIO controls on Day 34, Study 1

Body weight change -10.3% Mean percent change after 48 days of ALN1003, Study 1

Market Reality Check

Price: $3.19 Vol: Volume 17,097 is 1.18x th...

normal vol

$3.19 Last Close

Volume Volume 17,097 is 1.18x the 20-day average of 14,434, indicating modestly elevated trading interest pre‑announcement. normal

Technical Last close at 3.19 is above the 200-day MA of 3.04, sitting between the 52-week low of 1.3137 and high of 6.2.

Peers on Argus

Peers in Biotechnology showed mixed moves (e.g., APVO +2.95%, XBIO +7.2%, ADTX -...

Peers in Biotechnology showed mixed moves (e.g., APVO +2.95%, XBIO +7.2%, ADTX -4.55%, GRI -1.43%), suggesting TCRT’s modest +1.59% pre-news gain reflected stock-specific positioning rather than a coordinated sector move.

Regulatory & Risk Context

Active S-3 Shelf · $50,000,000

Shelf Active

Active S-3 Shelf Registration 2025-11-07

$50,000,000 registered capacity

An effective mixed shelf filing dated 2025-11-07 registers up to $50,000,000 of primary securities plus registered resale shares. With cash and cash equivalents of about $1.9 million and runway into 2Q 2026 disclosed in recent filings, this shelf provides a mechanism for future capital raises that could be dilutive if utilized.

Market Pulse Summary

This announcement highlights positive non‑GLP proof‑of‑concept data for ALN1003 in diet‑induced obes...

Analysis

This announcement highlights positive non‑GLP proof‑of‑concept data for ALN1003 in diet‑induced obesity models, with dose‑related weight loss, liver biomarker improvements, and a roadmap toward IND‑enabling studies. Filings show cash and cash equivalents of about $1.9 million and runway into Q2 2026, alongside a mixed shelf for up to $50,000,000. Investors may track future financing steps, progression into larger animal studies, and any IND‑enabling milestones.

Key Terms

non-glp, masld, pharmacokinetics

3 terms

non-glp medical

"announced early data from two non-Good Laboratory Practice (non-GLP) diet-induced obesity"

Non-GLP describes laboratory studies or tests conducted without following formal government-quality and documentation standards called Good Laboratory Practice. For investors, non-GLP results can still show early promise—think of a rough prototype or internal check—but they carry more uncertainty and usually won’t be accepted by regulators as definitive evidence, so they require confirmatory, GLP-compliant work before being relied on for approvals or major financial decisions.

masld medical

"metabolic dysfunction-associated steatotic liver disease (MASLD, a type of fatty liver disease)"

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition where excess fat builds up in the liver due to underlying metabolic problems like insulin resistance, obesity, or high blood lipids. Think of the liver like a kitchen filter getting clogged with grease; over time that buildup can reduce function and lead to inflammation or scarring, which matters to investors because it signals a large, growing market for diagnostics, treatments, and related medical services.

pharmacokinetics medical

"purpose of the first study was to evaluate the pharmacokinetics (PK) and tolerability"

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

AI-generated analysis. Not financial advice.

• The lead drug candidate, ALN1003, showed dose-related body weight loss and favorable body composition changes in the DIO mouse model
• ALN1003 also demonstrated reductions in liver weight and improvements in select biomarkers associated with liver injury compared to untreated mice
• Efforts to conduct additional preclinical studies, pursue optimized formulations and refine manufacturing processes are ongoing
  
  

FORT LAUDERDALE, Fla., March 02, 2026 (GLOBE NEWSWIRE) -- Alaunos Therapeutics, Inc. (Nasdaq: TCRT), an early-stage biotechnology company, today announced early data from two non-Good Laboratory Practice (non-GLP) diet-induced obesity (DIO) mouse studies evaluating ALN1003, the Company’s lead small-molecule drug candidate for treating obesity and related conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD, a type of fatty liver disease). ALN1003 is an oral small-molecule drug being developed for a non-hormonal, non-incretin approach, unlike hormone-based treatments like GLP-1 drugs. We conducted two separate studies using a standard diet-induced obesity (DIO) mouse model in male C57BL/6 mice maintained on a high-fat diet (60% of calories from fat). Highlights from these studies include dose-dependent body weight loss with favorable body composition changes, reductions in liver weight, decreases in liver injury enzymes (ALT, AST and ALP) and other liver-related biomarker, and improvement in metabolic biomarkers (e.g., glucose and total cholesterol). Collectively, these findings suggest encouraging metabolic effects of ALN1003 in the DIO model.

These studies provide early signs of how the drug works and its potential safety profile that will help guide the Company’s ongoing preclinical work and chemistry, manufacturing, and controls (CMC) initiatives. Key findings from these studies are summarized below (nominal reported p-values are unadjusted for multiple comparisons):

DIO Study 1

The purpose of the first study was to evaluate the pharmacokinetics (PK) and tolerability of ALN1003 and to assess early proof-of-concept anti-obesity efficacy including changes in weight, metabolic biomarkers, and adipose remodeling. Mice received low, controlled oral doses of ALN1003, split into two doses each day. Measurements included daily body weight, food and water consumption at the cage level, and metabolic markers (blood collection after a 4-6 hour fast at end of study). All animals were observed prior to and after each dose administration. There were 12 mice in each group, with mice housed 3 per cage.

Relative to DIO controls, mean percent change in body weight for ALN1003-treated mice peaked at -12.9% (p<0.0001) on Day 34 and was -10.3% (p<0.0001) after 48 days of treatment. Peak reductions in absolute weight loss were observed by Day 13 and remained lower than DIO controls through Day 48 (p<0.0001 at selected timepoints).

Food and water consumption: ALN1003 reduced cumulative food consumption versus DIO control (347.5 g/cage vs 425.0 g/cage; nominal p<0.05). ALN1003 reduced water consumption (445.8 mL/cage vs 494.5 mL/cage; not statistically significant).

Liver and Fat Tissue: In this study, ALN1003 reduced liver weight compared to untreated mice by 43% (p<0.0001) and by 39% when expressed as a percentage of body weight (p<0.0001). Long-term administration of ALN1003 was associated with lower ALT (alanine aminotransferase; p<0.0001), AST (aspartate aminotransferase; nominal p<0.0001) and ALP (alkaline phosphatase; p<0.0001), with a trend toward lower total bilirubin (nominal p=0.058) compared to untreated mice.

An unblinded macroscopic visual review of organ morphology was conducted comparing the liver and adipose tissues of the DIO control to the ALN1003 treatment group. Relative to DIO controls, ALN1003-treated animals exhibited smaller, deep reddish-brown livers; reduced epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) depots consistent with decreased adiposity; and darker interscapular BAT with appearance consistent with reduced “whitening” of BAT.

Tolerability: ALN1003 was generally well tolerated throughout the study. Mild, short-term, reversible hypolocomotion was observed after dosing in approximately one-half of dose administrations. There were no similar observations in DIO control animals.

DIO Study 2

The second study conducted was a pilot study to evaluate palatability, tolerability, anti-obesity effects, body composition and PK of ALN1003 administered orally in drinking water at three dose levels in DIO mice. The study comprised a treatment period of 14 days and a PK period of 4 days. ALN1003 was administered at three dose levels: low, medium and high. The middle and highest planned doses were 3 and 9 times higher than the low dose, respectively. Measurements included daily body weight, food and water consumption at the cage level, and metabolic parameters (blood collection after a 4-6 hour fast at end of study). All animals were observed each day. There were 6 mice in each group (2 mice per cage).

Food and water consumption: ALN1003 reduced cumulative food intake in a dose-dependent manner over the 14-day treatment period. Cumulative food consumption in grams per cage was 84.5g, 80.8g, 76.7g and 56.7g (nominal p<0.05) for the DIO control, low, medium and high doses, respectively. Cumulative food consumption when normalized to body weight per cage was 87.9g, 85.6g, 86.7g and 73.6g for the DIO control, low, medium and high doses, respectively. ALN1003 reduced water intake significantly over the 14-day treatment period. Cumulative water consumption in milliliters per cage was 112.8 mL, 80.1 mL (nominal p<0.05), 71.1 mL (p<0.0001) and 63.5 mL (p<0.0001) for the DIO control, low, medium and high doses, respectively. Cumulative water consumption when normalized to body weight per cage was 116.9 mL, 84.9 mL, 80.5 mL and 80.3 mL for the DIO control, low, medium and high doses, respectively. Actual dose consumed is dependent on how much water mice drink. Actual doses consumed during the 14-day treatment period were consistent with planned doses, with variances to planned doses of +7.3%, -0.3% and -6.9% in the low, medium and high dose groups, respectively.

Body composition was assessed using a Bruker Minispec^TM LF90II Body Composition Analyzer (Bruker BioSpin, Billerica, MA, USA) and demonstrated dose-related changes that were driven primarily by fat loss but also included the loss of lean and fluid mass. The table below summarizes the mean percentage change from baseline through Day 17 in fat, lean and fluid as a % of body weight (BW) and mass in grams:

Mean % Change:	Control		Low		Medium		High
D17 Fat% of BW	+2.4%		-1.5%		-5.4%		-21.9%c
D17 Lean% of BW	-1.3%		+2.4%		+4.6%		+17.2%c
D17 Fluid% of BW	+0.4%		-9.3%		-12.0%		-25.7%b
D17 Fat in grams	+4.7% (+0.9g)		-1.8% (-0.4g)		-12.3% (-2.5g)b		-44.6% (-8.9g)c
D17 Lean grams	+1.9% (+0.5g)		+2.2% (+0.6g)		-4.1% (-1.1g)a		-18.8% (-5.0g)c
D17 Fluid grams	+2.7% (+0.1g)		-9.6% (-0.4g)		-18.8% (-0.7g)a		-47.3% (-1.8g)c

Significance of comparison to Control group: a: nominal p<0.05; b: nominal p<0.001; c: p<0.0001

Liver and Fat Tissue: At end of study Day 18, including the 14-day treatment period plus the PK period, dose-related reductions in liver weights compared to DIO control were -6.8%, -20.5% and -55.0% (nominal p<0.01) in the low, medium and high dose groups, respectively. Reductions in liver weights expressed as a percentage of body weight relative to DIO control were -2.6%, -12.0% and -32.6% (nominal p<0.05). Liver enzymes showed no statistically significant change after 18 days; gross liver appearance suggested reduced fat accumulation. Histological analyses of liver and adipose tissues are planned.

An unblinded macroscopic visual review of organ morphology was conducted comparing the liver and adipose tissues of the DIO control to the high dose group. This analysis showed reductions in white fat depots (such as epididymal white adipose tissue, or eWAT, and inguinal white adipose tissue, or iWAT) and an interscapular BAT appearance consistent with reduced “whitening” in the ALN1003 tissues vs DIO control. Review of liver images suggested less visible fat accumulation and smaller, deep red-brown livers compared to DIO control.

Metabolic parameters: In this study, the highest-dose group showed lower blood sugar (glucose; 197 mg/dL in high dose vs 320 mg/dL in DIO control; p<0.0001) and lower total cholesterol (162 mg/dL in high dose vs 209 mg/dL in DIO control; nominal p<0.05). HDL-C (high-density lipoprotein cholesterol), the dominant lipoprotein in DIO mice, also decreased to 130 mg/dL in high dose vs 165 mg/dL in DIO control; nominal p<0.05.

Tolerability: ALN1003 was generally well tolerated throughout the study; however, on Day 16 (during the PK portion of the study), two mice in the high-dose group were noted to be slightly dehydrated for the remainder of the study, although they otherwise appeared normal.

Important Context and Model Limitations

• Behavior-coupled dosing in unrestricted (ad libitum) drinking-water studies: In this paradigm, ALN1003 caused dose-related loss of appetite and thirst (anorexia/hypodipsia), leading to avoidance of medicated water. Despite actual doses consumed approximating planned doses in this study, reductions in drinking may confound attribution of weight loss solely to drug exposure in this model.
  
  

“These early non-GLP data support ALN1003’s potential as a non-hormonal treatment to achieve meaningful body weight loss with favorable body composition changes and select liver-related findings,” said Holger Weis, CEO of Alaunos. “We are focused on additional preclinical studies, optimizing formulations and refining manufacturing processes as we advance toward studies to enable an Investigational New Drug (IND) application. ALN1003 has the potential to offer a new option for patients seeking alternatives to hormone-based obesity drugs.”

Development Roadmap

The findings from these two studies support the Company’s strategy to focus on additional preclinical studies and CMC activities to optimize formulations while maintaining effective overall drug levels. We are also planning to conduct studies to better understand mechanisms of ALN1003, including measuring liver fat levels and scoring MASLD severity of the liver in a blinded manner. We are planning to further refine manufacturing processes and to run a small-scale production run based on these improvements. Thereafter, a larger scale production run is planned. In parallel, the Company has initiated a computational chemistry program to design, make, and test ALN1003 variations to strengthen the Company’s intellectual property and assess next-generation compounds. These initiatives, including large animal pharmacokinetic studies, will inform plans to conduct IND enabling studies.

As of September 30, 2025, the Company had cash and cash equivalents of approximately $1.9 million. The Company’s current cash runway extends into the second quarter of 2026. The Company intends to pursue additional financing to support continued operations and advancement of its preclinical obesity and metabolic program.

About Alaunos Therapeutics, Inc.
Alaunos Therapeutics is a biotechnology company focused on developing novel therapeutics. The Company’s obesity and metabolic disorders program is advancing ALN1003, an oral small-molecule candidate designed to offer a differentiated, non-hormonal approach compared with currently available therapies.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as “may,” “will,” “could,” “expects,” “plans,” “anticipates,” “believes” or other words or terms of similar meaning. These statements include, but are not limited to, statements regarding the Alaunos Therapeutics, Inc.'s (“Alaunos” or “the Company”) business and strategic plans, the timing of the Company's research and development programs, including potential data read out dates as well as any potential patent filings for the Company’s obesity program.

These forward-looking statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially. Important factors that could cause actual results to differ materially include, but are not limited to: changes in the Company’s operating plans that may impact its cash expenditures; uncertainties built into research and development such as preclinical mouse data not translating to human trials, or challenges in scaling up formulations, including the risk that early non-GLP study results may not be replicated in confirmatory studies or pose safety concerns in IND-enabling studies; delays or failures in future studies; whether Alaunos’ product candidates will advance further in the clinical trial process, including getting approval by the U.S. Food and Drug Administration (FDA) or other foreign health authority to conduct clinical trials and whether and when, if at all, they will receive final approval from the FDA or equivalent foreign regulatory agencies and for which uses; challenges to the strength and enforceability of Alaunos’ intellectual property rights (such as patent disputes); competition from other pharmaceutical and biotechnology companies (including in the crowded obesity treatment market); funding shortages or market changes affecting our cash needs; tolerability issues from drug administration; the inherent uncertainties in drug development, including potential failures optimizing formulations, mechanistic studies, or large-animal pharmacokinetics that could delay IND-enabling activities; manufacturing and supply chain disruptions related to CMC work; and other factors discussed in our latest Form 10-Q and Form 10-K filed with the Securities and Exchange Commission (SEC). Forward-looking statements may also be protected if they are immaterial.

We caution you not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Except as required by law, Alaunos undertakes no obligation to update these statements to reflect events that occur or circumstances that exist after the date hereof.

Investor / Media Contact
ir@alaunos.com

FAQ

What weight loss did TCRT report for ALN1003 in the March 2, 2026 DIO mouse studies?

ALN1003 produced dose-dependent weight loss, peaking at -12.9% body weight on Day 34. According to the company, treated mice were ~-10.3% lighter after 48 days, with earlier absolute reductions observed by Day 13 versus DIO controls.

How did ALN1003 affect liver measurements and biomarkers in the TCRT preclinical data?

ALN1003 reduced liver weight up to -55.0% in high-dose mice and lowered ALT/AST/ALP. According to the company, liver appearance and enzyme decreases suggested reduced fat accumulation and improved liver-related biomarkers.

What metabolic improvements did TCRT observe with ALN1003 in the DIO mouse model?

High-dose ALN1003 lowered fasting glucose to 197 mg/dL from 320 mg/dL and reduced total cholesterol to 162 mg/dL. According to the company, these changes were statistically significant versus DIO controls in the pilot study.

Were there tolerability or safety concerns reported for ALN1003 in the March 2, 2026 release?

ALN1003 was generally tolerated but caused reversible hypolocomotion and dose-related anorexia/hypodipsia. According to the company, two high-dose mice were slightly dehydrated during the PK phase, and lean/fluid losses were noted at high dose.

What limitations did the company note about the ALN1003 preclinical studies for TCRT?

The company cautioned results are from non-GLP DIO mouse studies where reduced drinking may confound exposure-driven weight loss. According to the company, further blinded histology and IND-enabling studies are planned to address limitations.

How much cash did TCRT report and how long is the runway after the ALN1003 update?

TCRT reported approximately $1.9 million in cash and cash equivalents as of Sept 30, 2025, with a stated runway into the second quarter of 2026. According to the company, additional financing is intended to continue operations.