Our Science

Fat tissue is a remarkably plastic organ system comprised of different functional types of adipocytes. On one hand are the well-known white adipocytes, which store excess calories as triglycerides in large lipid droplets for use in times of energy shortage. On the other hand are the energy-consuming, thermogenic adipocytes, which represent the focus of Embark Biotech.

Thermogenic, or heat-producing, adipocytes are highly specialized fat cells fine-tuned through evolution to take up significant amounts of glucose and fatty acids from the blood to burn as fuel in the mitochondria. This unique feature of safely removing excess energy from the blood by oxidation in thermogenic adipocytes is physiologically regulated by exposure to cold temperatures as well as the circadian clock.

At Embark Biotech, our aim is to safely and potently harness this powerful, energy-dissipating cell type for developing pharmacotherapies to address clinical unmet needs within the metabolic diseases sphere.

  • 1/3: Target discovery principle

  • 2/3: EMB1 program

  • 3/3: Target discovery proof-of-concept

  • Embark _ Illustration _ Principle

    Can we identify novel receptors that regulate adipocyte metabolism?

    Embark Biotech is a platform company with expertise ranging from early target discovery to mode-of-action and preclinical validation in relevant disease models.

    We identify novel cell surface receptors that physiologically regulate fat tissue calorie-burning and glucose and lipid uptake. Candidates receptors are prioritized via integration of in-house datasets from disease-relevant animal models and human genetic disease associations. Upon identification of a strong, novel target, we employ peptide and small molecule chemistry approaches to engineer selective modulators of these receptors tailored for therapeutic application.

  • Embark _ Illustration _ EMB1

    New mode-of-action of food-intake and energy expenditure regulation

    EMB1 is a previously undescribed adipocyte G-protein coupled receptor. In addition to inducing adipose energy expenditure, it has remarkable ability to reduce hyperphagia via activation of neuronal populations in the brain stem.

    Embark Biotech has developed proprietary, highly selective, in vivo-validated EMB1 agonists that profoundly reduces hyperphagia and increase adipose insulin-independent glucose uptake and energy expenditure, leading to significant weight loss and improved cardiometabolic health.

    We are currently in pre-clinical development in preparation for first-in-man trials.

  • Embark _ Illustration _ EMB2

    Novel energy-expenditure target shows proof-of concept of discovery platform

    In our target discovery platform, we have identified GPR3 as an important regulator of thermogenic adipose activity.

    GPR3 is a constitutively active G-protein coupled receptor that increases intracellular cAMP levels. On thermogenic adipocytes, this leads to heightened lipid and glucose uptake from the blood stream and increased mitochondrial energy expenditure.


Pipeline

Tidslinje _ sort

Pipeline

Embark Biotech is currently working on two targets identified in our discovery platform.

EMB1 is a long-lived peptide modality for the treatment of hyperphagia. We have successfully finished lead optimization, and are now in early non-clinical development.

EMB2 is a small molecule modality energy expenditure activator that we envision positioned for obesity treatment. EMB2 is in early lead-optimization phase.

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Articles

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  • Cell
  • Volume 184
  • Number 13
  • June 24, 2021

Novel energy-expenditure target

Inducible genetic activation of GPR3 in brown adipocytes of obese mice robustly boosted energy expenditure that drove decreases in fat mass and overall bodyweight, and completely corrected glycemic control without affecting the cardiovascular system.

Findings from patient-derived cells validated GPR3 as a powerful activator of human brown adipocytes and indicate that GPR3 might offer the opportunity to safely and potently leverage the calorie-burning power of these highly specialized fat cells to counteract metabolic disease.

The scientific work was done in collaboration with the Gerhart-Hines laboratory at the University of Copenhagen and an international team of researchers from Europe and the US. The resulting paper was published in Cell and featured on the cover of the July 2021 issue.