PRECLINICAL DATA LEMBAS EDGE™
Conducted by scientists from Lembas Bio and Tel Aviv University, including Eden Goldfarb, Lucia Adriana Lifshits, Marina Abramova, Daniel Zvi Bar,
Dr. Zohar Barbash, Eyal Akiva, and Maayan Gal.
Reviewed by the Lembas Scientific Advisory Board.
RESEARCH OVERVIEW
This page summarizes preclinical research evaluating LMB-P52, a lead gut-active peptide candidate developed by Lembas.
The study explored whether food-grade peptides can interact with intestinal nutrient-sensing pathways involved in GLP-1 secretion, satiety signaling, food intake, and body weight regulation.
The research included computational peptide design, cell-based screening, acute hormone profiling in mice, and a 28-day diet-induced obesity rat model.
The central question behind this work was:
Can food-grade peptides stimulate endogenous gut hormone signaling connected to appetite regulation?
Rather than acting as an external GLP-1 receptor agonist, the research focused on peptides designed to engage gut biology upstream, through nutrient-sensing pathways involved in the body’s natural hormonal response to food.
To develop novel peptides designed to induce satiety and aid in weight management through appetite regulation mechanisms, offering a non-pharmaceutical alternative for both initial weight loss and long-term weight maintenance.
OBJECTIVE
STUDY DESIGN
The research followed a staged preclinical process, moving from computational discovery to biological validation.
First, Lembas used AI/ML-guided peptide design and structural modeling to identify peptide candidates predicted to interact with intestinal nutrient-sensing receptors.
Next, the peptides were screened in intestinal endocrine cells to evaluate their ability to stimulate GLP-1 secretion.
The lead candidate, LMB-P52, was then evaluated in mice to measure short-term gut hormone response.
Finally, LMB-P52 was studied over 28 days in a diet-induced obesity rat model to evaluate changes in food intake and body weight.
RESULTS
Our computational design process generated a series of peptides with progressively increasing binding affinity to the target receptor.
This was tested in vitro using GLP-1 secretion in STC-1 cell line. The prediction received score that was used for LLM training.
Intestine administration of LMB-P52 in C57BL/6 mice (n=8), GLP-1 levels after 15 min increased compared to the control.
Levels of GIP, PYY, insulin and amylin were measured 60 minutes post-injection.
Leptin, secretin, and PYY displayed a distinct surge in levels 3 hours after injection.
Our top-performing peptide was advanced to in vivo studies, beginning with an acute mouse model to confirm hormonal engagement.
Subsequently, we evaluated its long-term weight loss effects in a DIO rat model, benchmarking its performance against Semaglutide.
LMB-P52 and semaglutide reduced food intake and body weight in DIO rats (n=6/group) over 28 days. Both treatments significantly differed from vehicle (P < 0.01).
CONCLUSIONS
We are offering a food-based, non-pharmaceutical approach addressing the global obesity epidemic.
The multi-target approach of these peptides mimics the body’s natural satiety mechanisms, potentially providing a unique and sustainable solution for weight management and metabolic health.