CCK

Chief Medical Officer Head of Regulatory Affairs SAN DIEGO, Sept. 10, 2024 /PRNewswire/ -- Aardvark Therapeutics, Inc., a biopharmaceutical company, announced the appointment of Manasi Sinha Jaiman, M.D., M.P.H. as Chief Medical Officer and Tom Bicsak, Ph.D., as Head of Regulatory Affairs today. Commenting on the new hires, Aardvark CEO Tien Lee, M.D. said, "These new key positions will significantly accelerate the development of our lead investigational asset, ARD-101, which is designed to suppress the signs and symptoms of hunger and help reduce the effects of obesity and other indications." ARD-101, Aardvark Therapeutics' lead compound, is a first-in-class small-molecule bitter taste receptor (TAS2R) pan-agonist. Oral ARD-101 is a largely gut-restricted compound that is thought to bind enteroendocrine cells to stimulate release of Cholecystokinin (CCK). CCK is normally released in response to large meals and stimulates the vagus nerve through the gut-brain axis to send signals of satiety to the brain. It has promising activity for patients with Prader-Willi Syndrome (PWS), a genetic disease associated with unabating hunger, i.e., hyperphagia. A defect in CCK production in PWS patients has been implicated as a key driver of hyperphagia. In addition to utility in treating PWS, the ability to suppress hunger could be useful in the treatment of general obesity in a way that complements the appetite suppressing abilities of the growing number of GLP-1 mimetics. Hunger is one of the key reasons that overweight people have trouble complying with diet regimens. Dr. Lee further commented, "We believe ARD-101 is a well-differentiated first-in-class drug candidate that is orthogonal and complementary to existing obesity drugs, which reduces hunger through the selective induction of gut-brain signaling. The novel mechanism of action and gut-restricted nature of ARD-101 contribute to its encouraging safety and tolerability profile, as well as its broad-spectrum of activity. These additions to our management team will help us to get this treatment to patients as quickly as possible." About Manasi Sinha Jaiman, M.D., M.P.H. Prior to joining Aardvark, Dr. Jaiman was Vice President at Vertex Pharmaceuticals and Chief Medical Officer of ViaCyte where she developed novel approaches in cell therapy. Previously she was an attending physician at Harvard Medical School and Massachusetts General Hospital, where she was responsible for the clinical care of pediatric endocrinology patients, including those with diabetes, metabolic disease, obesity, and Prader-Willi Syndrome. She also served as a co-investigator for several trials developing the bionic pancreas at Massachusetts General Hospital. Dr. Jaiman received her M.D. from Medical University of South Carolina and her M.P.H. from Tulane University School of Public Health and Tropical Medicine. She completed her pediatric residency at Dartmouth-Hitchcock Medical Center and her endocrinology fellowship, which focused on type 1 diabetes research, at Massachusetts General Hospital. Dr. Jaiman commented, "As a pediatric endocrinologist, the ability to directly impact the root causes of hyperphagia in PWS patients is an exciting opportunity because it aims to decrease the immense burden these patients and families face. My background in endocrinology with a focus on metabolic disease and diabetes makes this a particularly interesting science to be involved with at this exciting time." About Tom Bicsak, Ph.D. Dr. Bicsak is a regulatory affairs professional with nearly 35 years of experience in all phases of drug development. Prior to joining Aardvark, Dr. Bicsak worked at Biosplice, Elcelyx, Orexigen, Amylin, Dura, and Johnson & Johnson in therapeutic areas including endocrine/cardiometabolic disorders, hematology, immunology/inflammation, oncology, pulmonary/respiratory medicine, rare inherited diseases, renal disease, rheumatology/pain, and wound healing. He was a significant contributor to multiple marketing approvals in the United States and European Union, including Bydureon, Byetta, Contrave/Mysimba, Procrit/Eprex, Regranex, and Symlin. Dr. Bicsak received his B.A. in Biochemistry from Rutgers University and his Ph.D. in Chemistry from the University of California, San Diego. He completed postdoctoral studies in Reproductive Endocrinology at the University of California, San Diego. Dr. Bicsak said, "Much of my career has been focused on developing treatments for endocrinologic disorders and I am excited about the opportunity to work with a patient population in such desperate need of a new treatment alternative." About Prader-Willi Syndrome (PWS) PWS is a severe neuro-developmental disorder with an incidence of about 1 in 15,000-20,000 births. The disorder is caused by the loss of function of several genes located on chromosome 15. PWS impacts multiple organ systems and is characterized by metabolic, endocrine, and neurological dysfunction. One of the hallmark characteristics of PWS is hyperphagia-driven extreme and unrelenting hunger accompanied by developmental delays and musculoskeletal malformations. There are currently no approved therapies for the treatment of hyperphagia, which affects the health and quality of life of children and adults with PWS. About Aardvark Therapeutics, Inc. and ARD-101 Aardvark Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel, small-molecule therapeutics to activate innate homeostatic pathways for the treatment of metabolic diseases, inflammation, and other indications. Aardvark's lead investigational compound, oral ARD-101, is a potent bitter taste receptor (TAS2R) pan-agonist that stimulates enteroendocrine cells of the digestive tract to release multiple gut-peptide hormones including GLP-1 and the satiety hormone Cholecystokinin (CCK), which activates gut-brain neurologic signaling to mediate hunger. Data from ARD-101 studies supports its ability to reduce hunger when used alone or in combination with other currently available therapies. Based on promising clinical data from an ongoing ARD-101 trial, the FDA has granted the drug both Orphan Drug designation and Rare Pediatric Rare Disease designation in PWS. For more information visit . SOURCE Aardvark Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Depression is one of the most common mental illnesses in the world, but current anti-depressants have yet to meet the needs of many patients. Neuroscientists recently discovered a small molecule that can effectively alleviate stress-induced depressive symptoms in mice by preventing aversive memory formation with a lower dosage, offering a new direction for developing anti-depressants in the future. Depression is one of the most common mental illnesses in the world, but current anti-depressants have yet to meet the needs of many patients. Neuroscientists from City University of Hong Kong (CityU) recently discovered a small molecule that can effectively alleviate stress-induced depressive symptoms in mice by preventing aversive memory formation with a lower dosage, offering a new direction for developing anti-depressants in the future. "Depression affects millions of individuals worldwide, necessitating more effective treatments. Conventional methods, such as drug therapy with delayed onset of action and psychotherapy, have limitations in yielding satisfactory results for many patients. A pioneering advancement in treatment is urgently needed," said Professor He Jufang, Wong Chun Hong Chair Professor in Translational Neuroscience at CityU. Previous research found that stress leads to neural plasticity changes in brain's valence-coding systems ("valence" refers to the degree to which something is pleasurable or aversive), which are strongly associated with depression, post-traumatic stress disorders and anxiety disorders. Also, some studies revealed that depression is correlated with the hyperactivated amygdala. "However, the neural mechanism that mediates depression in amygdala is still poorly understood," said Professor He. Over the years, Professor He's research group has focused on memory formation and encoding studies. Previously, they discovered that cholecystokinin (CCK), a key neuromodulator, is crucial for inducing long-term potentiation (LTP) -- a lasting increase in communication strength between neurons -- to enable memory formation. They also found that the CCK and CCK-B receptors (CCKBR is one of three known types of CCK receptors in the central nervous system) mediate neuroplasticity, as well as visual and sound associative memory formation, in the auditory cortex, and trace fear memory formation in the amygdala. Other studies have found that CCKBR antagonist (which blocks the binding of the CCK and CCK-B receptors, thus inhibiting the effect of the binding) exhibited an anti-depressant effect in mice. So Professor He's group hypothesized that CCK might facilitate aversive memory formation by enabling LTP in the basolateral amygdala (BLA) -- a brain region involved in processing emotional memories and thought to be dysregulated in depression, thus enhancing the development of depression. In their latest study, they tested this hypothesis using various experimental methods, including in vitro electrophysiological recording, optogenetic manipulation, drug manipulation and behavioural analysis of mice, to examine the critical role of CCK and CCKBR in depression. They found that a CCKBR antagonist called YM022 had an anti-depressant-like effect by blocking neuroplasticity-caused aversive memory formation in mice. The results of the in-vitro recording in the BLA showed that the YM022 significantly suppressed neuroplasticity. The neuroplasticity induction rate reached 72.3% in the control group; but it was only 10.2% in the drug-treated group. Moreover, the team underwent a series of behavioural tests to determine the antagonist's efficacy. The results showed that depressive behaviours in mice treated with a CCKBR antagonist was reduced. "Remarkably, the YM022 shows anxiolytic effects with a dose of 3.0 ug/kg, which is 3,000 times lower than the required dosage of current antidepressants," said Professor He. "These results indicate that CCKBR is a potential target for depression treatment, and that the selected antagonist, YM022, may be a good anti-depressant candidate due to its extremely small effective dose. This paves the way for targeted drug development that specifically addresses the abnormalities observed in the basolateral amygdala." Next, the research team will focus on the precise mechanisms and potential side effects of CCKBR antagonists to set the stage for future clinical trials involving human subjects. The research was supported by Hong Kong Research Grants Council, the Innovation and Technology Fund, the Health and Medical Research Fund, and the following charitable foundations: the Wong Chun Hong Endowed Chair Professorship, the Charlie Lee Charitable Foundation, and the Fong Shu Fook Tong Foundation.

SAN DIEGO, Aug. 3, 2023. Aardvark Therapeutics, Inc., a clinical stage biopharmaceutical company, today reported receipt of a Rare Pediatric Disease Designation in Prader-Willi Syndrome (PWS) from the FDA for its lead program ARD-101. 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. Prader-Willi Syndrome (PWS) PWS is a severe neurodevelopmental disorder with a prevalence of about 1 in 15,000-20,000 births. The disorder is caused by the loss of function of several genes located on chromosome 15. PWS impacts multiple organ systems and is characterized by metabolic, endocrine, and neurological dysfunction. One of the hallmark characteristics of PWS is morbid obesity in early childhood, accompanied by developmental delays and musculoskeletal malformations. Obesity in PWS is driven by hyperphagia and mitigated by strict control of food intake. Strict food control, if anything, exacerbates hyperphagia, anxiety and aggressive food-seeking behavior, which is most stressful for those afflicted as well as their caregivers. About PWS Clinical Study Previously, Aardvark had enrolled 12 subjects in a Phase 2 study of oral ARD-101 in PWS (ClinicalTrials.gov ID NCT05153434) led by Dr. Diane Stafford at Stanford Children's Health and Dr. Shawn McCandless at Colorado Children's Hospital. Based on promising results, Aardvark is enrolling additional subjects and exploring higher drug doses. About ARD-101 Aardvark's lead product, ARD-101, is a first-in-class oral composition that has shown promising activity in reducing hunger cravings in clinical studies and promoting weight loss in pre-clinical studies. ARD-101 is substantially gut-restricted and has minimal systemic exposure. It is postulated that ARD-101 conveys its systemic effects by activating secretion of several gut peptide hormones, including glucagon-like peptides-1 and -2(GLP-1, GLP-2), and cholecystokinin (CCK). Gut CCK is considered a "satiety signal" that acts via the gut-brain axis to control hunger. PWS patients have a normal CCK receptor but their CCK release from gut enteroendocrine I-cells in response to food is impaired, leaving PWS patients with a continuous sense of extreme hunger. Phase I studies demonstrated safety and tolerability in healthy human volunteers. Three Phase II studies have demonstrated an impact on hunger suppression. About Aardvark Therapeutics, Inc. Aardvark Therapeutics is a clinical stage biopharmaceutical company focused on developing novel small molecule therapeutics to activate innate homeostatic pathways for the treatment of metabolic diseases, inflammation, and other indications. Founded in 2017, the company has now advanced ARD-101 to Phase II clinical trials. Aardvark has multiple other programs in its pipeline. SOURCE Aardvark Therapeutics, Inc. Posted: August 2023