Aardvark Therapeutics

10/14/2024

What are the most fascinating discoveries with our lead candidate drug, ARD-101 to date?

1. ARD-101 engages receptors in the gut to help suppress appetite. But that’s not all. We saw that in addition to suppressing the appetite, ARD-101 also reduced low-density lipoprotein cholesterol, triglycerides, glucose, and hemoglobin A1C. These results indicated that ARD-101 could be useful in treating diabetes, hyperlipidemia, and obesity—the pillars of metabolic syndrome.

2. Further analysis and preclinical work also showed that ARD-101 profoundly lowers levels of pro-inflammatory cytokines - a truly exciting discovery.

3. Another surprising finding emerged from our early research. We showed that our drug is about 99% gut restricted—it stays in the gut, yet it conveys systemic effects, which is antithetical for most small-molecule drugs.

4. Because our lead candidate drug, ARD-101 has the potential to address both diabetes and inflammatory diseases, it could be the first product to truly address metabolic syndrome. We’ve known that both of these conditions overlap, but most of the therapeutics on the market affect only one or the other. It is unique to have a drug that affects both.

09/24/2024

Dr. Tien Lee, Founder and CEO of Aardvark Therapeutics, joined Judy Shaw on to talk about their innovative obesity drug, ARD-101. He shared how it stands out from other treatments, the encouraging data so far, and what their upcoming trials will focus on.

08/10/2024

Our science is focused on bitter taste receptors (Tas2Rs). Tas2R receptors are an evolutionary well conserved class of GPCRs expressed found in nearly all vertebrates. They are not just located in the mouth, but found on many cells throughout the body. Among other functions, they serve as surveillance for potential toxins and their activation elicits “anti-toxin” responses which may be utilized to convey therapeutic benefits.

Aardvark encapsulates our lead candidate, ARD-101, so that you can’t taste it on administration. It primarily limited to the digestive tract and works by stimulating bitter taste receptors to activate normal biological pathways by releasing gut peptide hormones, These hormones can suppress hunger, promote weight loss and reduce production of LDL, triglycerides, glucose, and hemoglobin (HbA1C) in animal models.

ARD-101 could be useful in treating inflammation, diabetes, hyperlipidemia, and obesity - the pillars of metabolic syndrome.

07/22/2024

Tien Lee, Founder and CEO of Aardvark Therapeutics, joins Nasdaq to celebrate our recent funding and discusses how our company specializes in gut brain interaction with a focus of inflammation and metabolism.

Tien Lee, Founder and CEO of Aardvark Therapeutics, sits down with Nasdaq’s Kristina Ayanian to celebrate their recent funding and discuss how the company specializes in gut brain interaction with a focus of inflammation and metabolism.

06/13/2024

Our lead product, ARD-101, is a first-in-class oral drug that is gut restricted and has low systemic exposure which contributes to its safety profile. While gut restricted, it conveys systemic effects via activation of gut peptide hormone secretion and gut-brain signaling. Preclinical and human clinical data support a broad safety window. Initial clinical trial results are consistent with the activity seen preclinical models of metabolic and inflammatory diseases and support continued clinical development.

01/26/2024

If you’ve ever “gone with your gut” to make a decision or felt “butterflies in your stomach” when nervous, you’re likely getting signals from an unexpected source: your second brain. Hidden in the walls of the digestive system, this “brain in your gut” is revolutionizing medicine’s understanding of the links between digestion, mood, health and even the way you think.

Scientists call this little brain the enteric nervous system (ENS) or the gut-brain axis. And it’s not so little. The ENS is two thin layers composed of more than 100 million nerve cells lining your gastrointestinal tract from esophagus to re**um, which in turn mediates downstream signals to convey various systemic physiologic responses.

The ENS is vital to the proper function of the gastrointestinal tract. When there is insult or injury to it, the digestive process suffers. The ability to affect the ENS in a positive way to treat digestive disorders is our ongoing area of research.

is looking at the interaction between the biology of the digestive tract and the brain that is mediated through the vagus nerve. This communication via the gut-brain axis is important due to its role in integrating digestion, immunity regulation, coordination of neurotransmitter and hormone secretions.



SOURCE:

https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-brain-gut-connection

12/04/2023

We are pleased to announce that the FDA has granted Aardvark Therapeutics a Rare Pediatric Designation for the use of ARD-101 in Prader-Willi Syndrome (PWS).

FDA grants Rare Pediatric Disease Designation (RPD) for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. This designation means Aardvark is eligible for a Rare Pediatric Disease Priority Review Voucher when ARD-101 receives approval in PWS. The early clinical study results suggest a promising future for a new class of pharmaceuticals that could benefit people with insatiable hunger (hyperphagia) and aggressive food-seeking behaviors, as well as for obesity and metabolic conditions, which are prominent features of the rare genetic condition PWS. Thus far, no drug has been approved by the FDA to treat the hyperphagia associated with PWS. Aardvark Therapeutics was also awarded Orphan Drug Designation by the FDA.

Previously, Aardvark Therapeutics had enrolled 12 subjects in a Phase 2 study of oral ARD-101 in PWS led by Dr. Diane Stafford at Stanford Children’s Health and Dr. Shawn McCandless at Colorado Children’s Hospital. Based on promising results, Aardvark Therapeutics is now enrolling additional subjects (ages 17-65) and exploring higher drug doses.

For more information, please click the link in our bio.

11/27/2023

Bitter taste receptors are not just in our mouths! They are also found in our guts, which is the foundation for our research.

Bitter taste receptors (TAS2R) are found on enteroendocrine cells (specifically on I and L cells). Enteroendocrine cells (EEC’s) are dispersed as single cells along the gastrointestinal mucosa and represent the largest endocrine system of the human body.

The I cell and L cells are responsible for appetite control, GI mobility, energy homeostasis, bile acid, digestive enzyme release, and mucosal immunity.

How does our primary candidate, ARD-101 work? It stimulates these bitter taste receptors which are found on these enteroendocrine cells to secrete neuropeptides - which are natural regulators of metabolism, hunger, weight, and inflammation.

SOURCE:

Yu Y, Yang W, Li Y, Cong Y. Enteroendocrine Cells: Sensing Gut Microbiota and Regulating Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2020 Jan 1;26(1):11-20. doi: 10.1093/ibd/izz217. PMID: 31560044; PMCID: PMC7539793.

11/13/2023

ARD-101 is differentiated from other treatment options.

ARD-101 is gut-restricted with minimal systemic exposure, yet it conveys systemic effects by activating secretion of several gut peptide hormones, including GLP-1, GLP-2, and cholecystokinin (CCK).

Gut CCK has long been recognized as the "satiety signal", acting via the gut-brain axis, to control hunger. While PWS patients have a normal CCK receptor, their CCK release from gut enteroendocrine I-cells in response to food is impaired, leaving PWS patients with a continuous sense of extreme hunger.

"Aardvark has discovered a way to stimulate the release of naturally produced gut CCK. Early trial results show substantial inhibition of hunger symptoms, i.e. hyperphagia" says Tien Lee, MD, CEO of Aardvark.

09/21/2023

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

We know neuropeptides now for over 40 years as chemical signals in the brain. The discovery of neuropeptides is founded on groundbreaking research in physiology, endocrinology, and biochemistry during the last century and has been built on three seminal notions: (1) peptide hormones are chemical signals in the endocrine system; (2) neurosecretion of peptides is a general principle in the nervous system; and (3) the nervous system is responsive to peptide signals. These historical lines have contributed to how neuropeptides can be defined today: "Neuropeptides are small proteinaceous substances produced and released by neurons through the regulated secretory route and acting on neural substrates." Thus, neuropeptides are the most diverse class of signaling molecules in the brain engaged in many physiological functions.

There are over 100 known neuropeptides, representing the largest and most diverse class of signaling molecules in the nervous system.

SOURCE:

Burbach JP. What are neuropeptides?. Methods Mol Biol. 2011;789:1-36. doi:10.1007/978-1-61779-310-3_1