Aardvark Therapeutics, Inc. · NASDAQ:AARD
Aardvark Therapeutics — ObesityWeek Investor Webinar 2025
65 slides from Aardvark Therapeutics's conference presentation, Nov 6, 2025
Slide 1: ObesityWeek Investor Webinar November 5, 2025
ObesityWeek Investor Webinar November 5, 2025 Exhibit 99.1
Slide 2: Disclaimer
Disclaimer Aardvark Therapeutics, Inc. (the “Company”) does not (nor their respective affiliates, directors, members, officers, employees or agents) make any representation or warranty, express or implied, as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctnes
Slide 3: Our Agenda
Opening Remarks Tien Lee, MD Aardvark ObesityWeek Presentations Timothy Kieffer, PhD, Chief Scientific Officer, Aardvark Therapeutics Guest Speakers: Tony Lam, PhD, Professor at University of Toronto Caroline M. Apovian, MD, Co Director, Center for Weight Management and Wellness at Brigham and Women
Slide 4: Positioned for Execution & Growth
Positioned for Execution & Growth Suppressing Hunger to Treat Rare Metabolic Diseases and Obesity Rare Disease Hyperphagia in Prader-Willi Syndrome Obesity Epidemic Goal to address limitations of existing therapies Validated Market Opportunities Populations with severe unmet medical needs Balance Sh
Slide 5: Hunger vs Appetite: Distinct Neural Pathways
CCK, cholecystokinin; GLP-1, glucagon-like peptide-1 Hunger vs Appetite: Distinct Neural Pathways Appetite Hunger Penalty avoidance Mediated by local gut hormones like CCK Signaling through the Gut-Brain Axis Reward-based Mediated by circulating hormones like GLP-1 Targeted systemically through the
Slide 6: Driving Innovation Across Indications
Driving Innovation Across Indications HERO TRIAL Hyperphagia ARD-101 Population & Indication Prader-Willi Syndrome PHASE 3 Trial Ongoing Key Goals Expand treatment options Treat high unmet medical need POWER TRIAL Weight Maintenance ARD-201 Population & Indication Obesity PHASE 2 Expected Initiation
Slide 7: ObesityWeek 2025 ARD-201
A: aardvark “7° therapeutics ObesityWeek 2025 ARD-20]
Slide 8: ARD-201: Essential Combination for Weight Loss Potential
ARD-201: Essential Combination for Weight Loss Potential 8 EEC Gut-Peptides ARD-101 DPP-4 TAS2R DPP-4 Inhibitor ARD-101 ARD-201 = ARD-101 + DPP-4i ARD-101 is an agonist of TAS2Rs, located on enteroendocrine cells in the gastrointestinal tract DPP-4 is an enzyme that degrades gut peptides, like GIP a
Slide 9: ARD-201 Induces Transformational Weight Loss
~19% WEIGHT LOSS ARD-201 PRECLINICAL (1)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences) 9 Gold-standard diet-induced obesity mouse model ARD-201 induced ~19% weight loss in 30 days Relative potency translationally predictive(1) ARD-201 Induces Transformational Weight Loss
Slide 10: ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy
ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy ARD-201 PRECLINICAL DIO-B6 MOUSE MODEL (*)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences) 10 Off tirzepatide Weight Regain ARD-201 is comparable to continued tirzepatide treatment Combination with ARD-201 exceeds
Slide 11: ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy
ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy ARD-201 PRECLINICAL DIO-B6 MOUSE MODEL (*)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences) 11
Slide 12: ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy
ARD-201 Prevents Weight Regain & Enhances GLP-1RA Efficacy ARD-201 PRECLINICAL DIO-B6 MOUSE MODEL DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences) 12
Slide 13: ARD-201 Delivers Glucose Control Comparable to Tirzepatide
ARD-201 Delivers Glucose Control Comparable to Tirzepatide(1) DIO-B6 MOUSE MODEL ARD-201 PRECLINICAL (1)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences) Combination of ARD-201 + low dose tirzepatide delivers the most rapid glucose clearance compared to other treatment coho
Slide 14: Phase 2 Trial of Low-Dose ARD-101 Demonstrates Weight Loss Benefits
Phase 2 Trial of Low-Dose (200 mg) ARD-101 Demonstrates Weight Loss Benefits Independent of a DPP-4 Inhibitor Figure 14. Effect of ARD-101 on Body Weight in Adults with Obesity 14 ARD-101 resulted in a significant reduction in hunger-related scores and food craving Trend in weight control with no av
Slide 15: ARD-201: Phase 2 Trials Designed to Address Gaps in Obesity Treatment
POWER Trial Expected Initiation 2H 2025 Potential maintenance-phase solution as an off-ramp for GLP-1RA therapy responders Target high-risk window when patients are vulnerable to weight regain and metabolic reversal Weight Maintenance STRENGTH Trial Expected initiation 1H 2026 Potential oral alterna
Slide 16: ObesityWeek 2025 WE-868
A: aardvark “7° therapeutics ObesityWeek 2025 WE-868
Slide 17: WE-868 – A Novel Approach to Obesity Treatment
WE-868 – A Novel Approach to Obesity Treatment Terminal Lean vs. Fat Mass (%) WE-868 is a synthetic isoflavonoid designed to modulate cellular energy use Lowers oxidative phosphorylation, inducing utilization of stored glycogen thereby increasing energy expenditure Structurally distinct from classic
Slide 18: Greater than Expected Weight Loss in Phase 1b Trial of WE-868 + Bevacizumab
Greater than Expected Weight Loss Observed in Phase 1b Trial of WE-868 + Bevacizumab in Patients with mCRC WE-868 CLINICAL PHASE 1B PATIENTS WITH MCRC 18 19% of total subjects lost more than 15% of their initial weight 10.3% average weight loss over mean treatment duration of 92 days A Phase 1b Open
Slide 19: WE-868 Attenuates Weight Gain in Mice on a High Fat Diet
WE-868 Attenuates Weight Gain in Mice on a High Fat Diet (HFD)(1) WE-868 PRECLINICAL HIGH FAT DIET (HFD) MOUSE MODEL 19 Preservation of lean mass and loss of fat mass WE-868 dose-dependently blunted weight gain 19 WE-868 PRECLINICAL (1)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic B
Slide 20: WE-868 Induces Weight Loss in DIO Mice
WE-868 Induces Weight Loss in DIO Mice(1) DIO-B6 MOUSE MODEL Preservation of lean mass and loss of fat mass Significant weight loss observed with WE-868 20 WE-868 PRECLINICAL (1)DIO-B6 Mouse Model (Diet-Induced Obese B6 Mouse Model, Taconic Biosciences)
Slide 21: Tony Lam, PhD, Professor at University of Toronto
Tony Lam, PhD Professor at University of Toronto
Slide 22: Tony Lam Laboratory: Nutrient Sensing and the Gut-Brain Axis
Tony Lam Laboratory Nutrient Sensing and the Gut-Brain Axis
Slide 23: Obesity and Diabetes Prevalence
Obesity More than one billion people worldwide have obesity (650 million adults, 340 million adolescents and 39 million children) Diabetes 537 million people worldwide have diabetes
Slide 24: Lipid sensing activates a Gut-Brain Axis
Food Intake Glucose Homeostasis Wang et al. Nature, 2008 Cummings et al. J Clin Invest, 2006 Lipid sensing activates a Gut-Brain Axis
Slide 25: To CNS
To CNS Duca et al. Ce// Metab, 2015
Slide 26: Waise et al. Nature Rev Gastroenterol Hepatol, 2018
Waise et al. Nature Rev Gastroenterol Hepatol, 2018
Slide 27: Duca et al. Nature Commun, 2021
Duca et al. Nature Commun, 2021
Slide 28: Li & Barros et al. Nature Metab, 2024
Li & Barros et al. Nature Metab, 2024
Slide 29: Gut-Brain afferent axis vs. Direct GLP1r agonist effect in the Brain
Yue et al. Cell, 2024 Gut-Brain afferent axis vs. Direct GLP1r agonist effect in the Brain
Slide 30: Bitter Taste Receptor (TAS2R) & the Gut-Brain axis
Bitter Taste Receptor (TAS2R) & the Gut-Brain axis TAS2Rs are expressed in the small intestine TAS2R agonists increase intestinal CCK and GLP1 secretion in parallel to lowering food intake in rats Grau-Bove C et al. Nutrients 2020 PMID:33321802
Slide 31: Lab members
Lab members: Dr. Song-Yang Zhang Kyla Bruce Nick Garrido Dr. Zeyu Yang Melissa Wang Dorsa Moslemian Rachel Kuah Penny Wang Lisa Nash Toronto General Hospital Foundation
Slide 32: Caroline M. Apovian, MD
Caroline M. Apovian, MD Co Director, Center for Weight Management and Wellness at Brigham and Women’s Hospital
Slide 33: The Latest Trends in Obesity Clinical Development
The Latest Trends in Obesity Clinical Development Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM Co-director, Center for Weight Management and Wellness Brigham and Women’s Hospital Professor of Medicine Harvard Medical School Boston, Massachusetts
Slide 34: Center for Weight Management and Wellness
Center for Weight Management and Wellness Caroline M. Apovian, MD, FACN, FACP, DABOM Past President, The Obesity Society, 2018 Co-Director, Center for Weight Management and Wellness Brigham and Women’s Hospital Adipose Tissue and Nutrient Metabolism Core Co-Director, Boston Obesity Nutrition Researc
Slide 35: Clinical and Research Staff
Center for Weight Management and Wellness: Clinical and Research Staff
Slide 36: Obesity is a Disease: the body weight set point leads to adiposity
Obesity is a Disease: the body weight set point leads to adiposity Heymsfield SB, Wadden TA. N Engl J Med ;376:254-266 Pathways through Which Excess Adiposity Leads to Major Risk Factors and Common Chronic Diseases
Slide 37: Weight Loss at 1 Year: Lifestyle vs Pharmacotherapy
Weight Loss at 1 Year with High-Intensity Lifestyle Interventions or Pharmacotherapy Combined Lifestyle vs. Pharmacotherapy: Weight Loss at 1 Year Heymsfield SB, Wadden TA. N Engl J Med ;376:254-266
Slide 38: Hormonal and Neural Pathways That Regulate Food Intake
Interactions among Hormonal and Neural Pathways That Regulate Food Intake and Body-Fat Mass – Central Control of Body Weight Korner J, Leibel RL. NEJM 2003;349:926-8 Discovery of Leptin and the Neural Circuit that Controls Feeding: Framework for studying obesity alternative explanation to the notion
Slide 39: Defense of a Body Weight Set Point
Compensation for an Increase or Decrease in Body Weight by Increase or Decrease in Total Energy Expenditure Until Weight Is Regained or Lost – Leptin* Defends Adipose Mass TEE = 60% REE + 10% TEF + 30% NREE Leibel RL, et al. N Engl J Med 1995;332:621-628. DEFENSE OF A BODY WEIGHT “SET POINT” *The fe
Slide 40: Body continues to fight against weight loss
2009, 50 obese men and women Men 233 lbs/average Women 200 lbs/average Extreme low-calorie diet Optifast shakes + 2 cups of low-starch vegetables Total 500-550 kcal/d for eight weeks At 10 weeks: 30-lb ave. weight loss At year one: 11-lb ave. weight regain Reported feeling more hungry and preoccupie
Slide 41: Long-Term Persistence of Hormonal Adaptations to Weight Loss
Long-Term Persistence of Hormonal Adaptations to Weight Loss Changes in Weight from Baseline to Week 62 30-lb LOSS 11-lb GAIN 10 week weight-loss program Sumithran P, et al. N Engl J Med. 2011;365:1597-1604.
Slide 42: Weight Loss Produced Changes in Eight Hormones
14% Weight Loss Produced Changes in Eight Hormones That Encourage Weight Regain Mean fasting and postprandial levels of some peripheral signals at baseline and 62 weeks Reduced Increased Leptin - 65% Peptide YY Cholecystokinin Insulin Amylin Ghrelin Pancreatic polypeptide Gastric inhibitory polypept
Slide 43: Medical Treatment of Obesity
Medical Treatment of Obesity ©2010 by Cleveland Clinic Kashyap SR. Cleveland Clinic Journal of Medicine 2010;77:468-476. Mimic Hormonal Effects of Metabolic Surgery How gut hormones may contribute to lowering the body weight set point and regression of diabetes after Roux-en-Y Surgery
Slide 44: Gut–brain regulation of food intake
Müller TD, et al. Nat Rev Drug Discov. 2022 Mar;21(3):201-223. Gut–brain regulation of food intake
Slide 45: New drugs approach surgery outcomes
Retatrutide - CagriSema FDA-approved for Obesity 1 2 3 4 5 6 7 8 25+% Efficacy of Current and Pending Anti-obesity Drugs as Compared to Bariatric Surgery Mechanick JI, Apovian C, et al. Endocr Pract. 2019 Dec;25(12):1346-1359. Jastreboff AM, et al. N Engl J Med. 2022 Jul 21;387(3):205-216. Wilding J
Slide 46: Current Treatment Landscape with Tirzepatide
Current Treatment Landscape with Tirzepatide 0% 5% 10% 15% 20% 25% 30+% Weight Loss After Aronne LJ. FDA VI-0521 EMDAC 2010. Diet and Lifestyle New drugs and devices can reduce weight and weight-related comorbidities Lap Band Sleeve Gastrectomy Gastric Bypass Tirzepatide 23 kg = 22.5% WL Orlistat Ph
Slide 47: Mechanisms of action of gastrointestinal peptides for weight reduction
Mechanisms of action behind the weight-reducing effect of gastrointestinal peptides currently studied for weight reduction Holst JJ. Nat Metab. 2024 Oct;6(10):1866-1885.
Slide 48: Advantages of targeting GLP-1 and GIP
Advantages of targeting GLP-1 and GIP for weight management vs single agonism alone include: Increased satiety: Both GLP-1 and GIP play roles in regulating appetite and satiety. GLP-1/GIP receptor agonism can enhance feelings of fullness, leading to reduced food intake and decreased calorie consumpt
Slide 49: Current Unmet Needs
Current Unmet Needs
Slide 50: Side Effects for Liraglutide, Semaglutide, and Tirzepatide
SIDE EFFECTS for Liraglutide, Semaglutide, and Tirzepatide JAMA. 2015 Aug 18;314(7):687-99; N Engl J Med. 2021 Mar 18;384(11):989-1002; N Eng J Med 2022;387:205-216. SCALE (Liraglutide 3.0, placebo %) STEP-1 (Semaglutide 2.4, placebo %) SURMOUNT-1 (Tirzepatide 5/ 10/ 15, placebo %) Nausea 40.2/ 14.7
Slide 51: Next Frontier: Long-term weight maintenance on NuSH therapies
Next Frontier to Tackle: Long-term weight maintenance on NuSH therapies Efficacy of Nutrient Stimulated Hormonal Therapies (NuSH) has bridged the gap, evident for many years, in the treatment of obesity between lifestyle and older medications (average weight loss 5-10%) versus metabolic bariatric su
Slide 52: Weight regained after cessation of pharmacotherapy
Trials across various classes of medications, including potent antiobesity medications such as semaglutide, demonstrated that weight is substantially regained after cessation of pharmacotherapy Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya
Slide 53: Discussion
Discussion Are there any patients that successfully maintain when drugs are stopped? We know what happens on average but not if there are any who succeed Can we reduce doses of our NuSH therapies or try another different drug for maintenance? More research is needed – for this we really need to go b
Slide 54: What about body composition?
What about body composition? Weight loss estimates from multiple trials – baseline weight varies across studies *High protein diet data were not in patients with obesity **Bariatric Surgery patients start at higher BMI, thus greater weight loss. ***Data reflects patients in the body composition subs
Slide 55: Mass General Brigham
l=) } Mass General Brigham
Slide 56: Prader-Willi Syndrome Overview and Update
Prader-Willi Syndrome Overview and Update
Slide 57: Phase 3 Program: ARD-101 for Treatment of Hyperphagia in PWS
Novel Gut-Brain Approach Unmet Need in PWS Advancing Our Global Phase 3 In Phase 2, ARD-101 achieved encouraging results and was well-tolerated, supporting development in our global Phase 3 trial Hyperphagia is a significant burden for individuals with Prader-Willi Syndrome, who have limited therape
Slide 58: CCK is a Potential Target in the Treatment of Hunger in PWS
Hunger Anxiety Body Fat Constipation Inflammation CCK problems can lead to: (1) Moran, T. H., and S. Bi. 2006. Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors, Philos Trans R Soc Lond B Biol Sci, 361: 1211-8. (2) Cleveland Clinic, “Cholecystokinin.” 2024. (3) Br J Pharmacol. 2004 Apr;1
Slide 59: Oral ARD-101: Reduced Hunger in Prior Phase PWS Trial
Oral ARD-101: Reduced Hunger in Prior Phase 2 PWS Trial Average Change in Hunger and Food-Seeking Behavior During 28-Day Trial(1) ARD-101 was tested in PWS patients (ages 17 and older) in a 28-day trial Hunger was measured using the HQ-CT (Questionnaire to measure hunger in PWS) Early signs of impro
Slide 60: HERO: Hunger Elimination or Reduction Objective
HERO: Hunger Elimination or Reduction Objective EVALUATING Change in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score RANDOMIZATION SCREENING OLE PWS Patients W/Hyperphagia 10 years & older Open-Label Extension BASELINE MEASUREMENT WEEK 12 N=45 Treatment Arm A ARD-101 Treatment Arm B Plac
Slide 61: HERO Trial: Designed to Address Needs and Outcomes
HERO Trial: Designed to Address Needs and Outcomes 61 4 clinic visits and 3 telehealth check-ins Simple Schedule No need to fast or skip meals for the trial, and travel/lodging is covered Inclusive Design Same caregiver throughout the trial with minimal change to routine Stable Routine Standardized
Slide 62: The Need for Additional Options
The Need for Additional Options (1) Soleno Phase 3 data (DCCR, Prader-Willi Syndrome): ≥7-point clinically meaningful HQ-CT threshold achieved at 26 weeks (~6 months) (2) Butler MG et al., Front Endocrinol (2023). doi: 10.3389/fendo.2023.1168648 (3) Prescribing Information, VYKAT XR (Diazoxide Exten
Slide 63: A Discussion with Prader-Willi Syndrome Association | USA
A Discussion with Prader‐Willi Syndrome Association | USA Manasi Jaiman, MD Chief Medical Officer Aardvark Therapeutics Stacy Ward, MS, BCBA Chief Executive Officer PWSA | USA Dorothea Lantz Director of Community Engagement PWSA | USA
Slide 64: Q&A
Q&A A: aardvark “7° %@ therapeutics
Slide 65: Obesity Pipeline Q&A
Obesity Pipeline Q&A A: aardvark “7° %@ therapeutics
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