Oral therapy designed to minimize CNS side effects shows dual activity in weight loss and smoking cessation models without muscle loss
MIAMI, FLORIDA / ACCESS Newswire / June 30, 2025 / MIRA (NASDAQ:MIRA) today announced new animal study results from SKNY-1, a next-generation oral therapeutic under definitive agreement for acquisition. In a zebrafish model that mimics human obesity and craving behaviors, SKNY-1 demonstrated weight loss, suppression of appetite and craving for high-calorie diets, and reversal of nicotine-seeking behavior-all achieved within six days of oral treatment.
SKNY-1 is being developed as an oral alternative to GLP-1 injectables, which are often limited by nausea, GI discomfort, injection reaction, and growing concerns around muscle loss. Unlike GLP-1s, which reduce both fat and lean mass, SKNY-1 demonstrated significant weight loss with preserved muscle. It was specifically designed to minimize engagement with central nervous system pathways implicated in the psychiatric side effects observed in some smoking cessation therapies and first-generation CB1-targeting weight-loss drugs. The data support SKNY-1’s potential as a differentiated oral therapy addressing two of the world’s leading causes of preventable death.
The study was conducted in an obesity and craving model in Ob42 Strain-mc4r (G894C) mutated zebrafish following six days of oral treatment with two doses of SKNY-1 and was compared to normal controls.
Key Results
Weight Loss and Muscle Preservation:
SKNY-1 reduced body weight by approximately 30% after just six days of oral treatment. Treated animals ended up weighing about 10% less than healthy controls. Importantly, this weight loss was not accompanied by muscle density changes-suggesting SKNY-1 helps burn fat while preserving lean body mass.
Metabolic Activity and Ventilation Rate:
Treated animals showed an increase in breathing rate, which is a reliable signal that their metabolism was speeding up. This aligns with the observed weight loss and suggests that SKNY-1 helps the body burn more energy.
Liver and Lipid Profile Improvements:
In untreated obese animals, fat buildup in the liver was about 50% higher than normal. SKNY-1 reversed this buildup, bringing liver fat back to healthy levels. At the same time, cholesterol levels-including LDL (‘bad’ cholesterol) and HDL (‘good’ cholesterol)-also returned to normal, without affecting fat levels in the blood. This points to improved fat processing without disrupting the body’s overall metabolic balance.
Appetite, Craving, and Compulsive Eating:
Obese animals were eating 2-3 times more high-calorie food than normal. SKNY-1 dose-dependently reduced this behavior-high-dose animals ate less than healthy controls. The drug also made the animals less likely to pursue food in stressful environments and reduced obsessive food-seeking in tests designed to measure craving.
Nicotine Craving and Compulsivity:
SKNY-1 significantly reduced the desire to seek out and consume nicotine. Treated animals were less willing to pursue nicotine even in stressful conditions, and they no longer showed a preference for environments linked to nicotine rewards. At the high dose, their behavior matched that of healthy animals with no nicotine craving.
Neurohormonal Balance:
Obese animals had extremely high levels of leptin (a hunger-regulating hormone) and unusually low levels of ghrelin (the ‘hunger signal’). This imbalance often leads to constant hunger and poor appetite control. SKNY-1 normalized both hormones, improving the body’s ability to regulate hunger and energy use.
Brain Dopamine Regulation:
Obese animals had too much dopamine in the brain, likely tied to increased reward and cravings. SKNY-1 reduced these dopamine levels-but only at the lower dose. The high dose did not affect dopamine, suggesting the drug can reduce craving without overstimulating the brain.
“Within just six days, we saw robust behavioral, hormonal and metabolic changes, including weight loss, improved fat metabolism, and reversal of craving-like behaviors,” said Dr. Itzchak Angel, Chief Scientific Advisor at MIRA. “These results highlight SKNY-1’s potential to address both obesity and nicotine addiction through unique and safe pathways.”
A Differentiated Approach to Two Major Markets
Current weight-loss therapies like semaglutide and tirzepatide are effective but limited by gastrointestinal side effects, injectable administration, and loss of lean mass. Smoking cessation treatments such as varenicline and bupropion carry psychiatric warnings and offer modest long-term quit rates.
SKNY-1 was designed to overcome these limitations. It selectively modulates CB1 receptors by blocking β-arrestin signaling-associated with cravings and compulsive behavior-while preserving G-protein signaling, which supports emotional and cognitive stability. The compound also activates CB2 receptors and mildly inhibits MAO-B without affecting MAO-A, supporting a favorable safety and tolerability profile.
“These results position SKNY-1 as a potentially disruptive oral treatment,” said Erez Aminov, CEO of MIRA. “Its ability to reduce body mass, suppress cravings, and preserve muscle-all through oral administration-makes it a compelling therapeutic candidate as we move toward closing the acquisition and preparing for IND-enabling studies.”
The Company believes these findings further support the advancement of SKNY-1 toward Investigational New Drug (IND)-enabling studies. With obesity and smoking representing two of the leading causes of preventable death-and a combined global market opportunity exceeding $200 billion-MIRA intends to prioritize SKNY-1 as a potential cornerstone asset pending completion of the acquisition of SKNY Pharmaceuticals, Inc.
About MIRA Pharmaceuticals, Inc.
MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA) is a clinical-stage pharmaceutical company focused on the development and commercialization of novel therapeutics for neurologic, neuropsychiatric, and metabolic disorders. The Company’s pipeline includes oral drug candidates designed to address significant unmet medical needs in areas such as anxiety, cognitive decline, neuropathic pain, obesity, and addiction.
Cautionary Note Regarding Forward-Looking Statements
This press release and the statements of MIRA’s management related thereto contain “forward-looking statements,” which are statements other than historical facts made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any statements in this press release that are not historical facts may be deemed forward-looking. Any forward-looking statements in this press release are based on MIRA’s current expectations, estimates, and projections only as of the date of this release and are subject to a number of risks and uncertainties (many of which are beyond MIRA’s control) that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including related to MIRA’s potential merger with SKNY Pharmaceuticals, Inc. These and other risks concerning MIRA’s programs and operations are described in additional detail in the Annual Report on Form 10-K for the year ended December 31, 2024, and the Form 14A filed by MIRA on June 18, 2025, and other SEC filings, which are on file with the SEC at www.sec.gov and on MIRA’s website at https://www.mirapharmaceuticals.com/investors/sec-filings. MIRA explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
Contact:
Helga Moya
info@mirapharma.com
(786) 432-9792
SOURCE: MIRA Pharmaceuticals
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