T3D Therapeutics Announces Presentation of Final Phase 2a Results of T3D-959 in Mild to Moderate Alzheimer’s Subjects at the 2018 Alzheimer’s Association International Conference

Effects of a PPAR Delta/Gamma Agonist, T3D-959, on Metabolic and Cognitive Functions in Mild to Moderate Alzheimer’s Disease Subjects John Didsbury, PhD1 †, Hoda Gabriel, PMP1, Warren Strittmatter, MD1 and Stan Chamberlain, PhD1 (1)T3D Therapeutics, Inc., Research Triangle Park, NC, USA Alzheimer's Association International Conference 2018 Chicago, IL July 22, 2018 O #26159 1 T3D Therapeutics, Inc. Disclosures John Didsbury, Ph.D. • Employee of T3D Therapeutics, Inc. • Shareholder inT3D Therapeutics, Inc. CME/CE credits will not be awarded for this presentation . 2 T3D Therapeutics, Inc. PHOTO, VIDEO AND AUDIO POLICY Photography is welcome in this presentation. Video and audio recording are prohibited. T3D Therapeutics, Inc. Forward-Looking Statements Statements contained in this presentation that are not statements of historical fact may be deemed to be forward looking statements. Without limiting the generality of the foregoing, words such as “may,”“will,” “expect,” “believe,” “anticipate,”“intend,”“could,”“estimate”or “continue”are intended to identify forward-looking statements. Readers are cautioned that certain important factors may affect the Company’sactual results and could cause such results to differ materially from any forward looking statements which may be made in this presentation or which are otherwise made by or on behalf of the Company. Factors which may affect the Company’sresults include, but are not limited to, product demand, market acceptance, impact of competitive products and prices, product development, commercialization or technological difficulties, the success or failure of negotiations and trade, legal, social and economic risks. 4 T3D Therapeutics, Inc. Overview of T3D-959 . 5 A. Preclinical Studies B. Early Clinical Development C. Phase 2a Exploratory Feasibility Study of T3D-959 in Mild to Moderate AD (T3D959-201) D. Future Clinical Development T3D-959: • Orally administered indane acetic acid as a sodium salt • Brain penetrant, 20h plasma T1/2 • PPARδ (delta) / PPARγ (gamma) dual nuclear receptor agonist. Regulation of glucose and lipid metabolism o Primary target PPARδ 19nM EC50 on human receptor (regulator of energy expenditure) o Secondary target PPARγ 297nM EC50 on human receptor (regulator of energy storage) T3D Therapeutics, Inc. PPAR Agonists in AD – A Brief Summary 6 PPAR gamma selective agonists - originally developed to treat Type 2 Diabetes by improving systemic Insulin Resistance (IR) PPAR gamma selective agonists were engineered to limit central exposure PPAR gamma has limited regional expression in the brain Rosiglitazone – PPAR gamma (γ) selective agonist (thiazolidinedione) • Poor brain penetration: only 0.0045% of oral dose gets into brain (rat) • ‘Failed’ Phase 3 AD trial demonstrated that peripheral PPAR modulation does not provide efficacy in AD Pioglitazone – PPAR gamma (γ) selective agonist (thiazolidinedione) • Some success in Phase 2 AD trial in subjects with Type 2 Diabetes co-morbidity • TOMORROW Phase 3 failure in cognitively normal subjects – failure of drug or failure of genetic algorithm for predicting risk to progression to AD? T3D-959 - Potent PPAR delta / gamma agonist • PPAR delta – high ubiquitous brain expression • Different chemical class than Rosiglitazone or Pioglitazone (equivalent potency on gamma) • Brain penetrant: rat brain/plasma ratio = 35% at 1 hr and 12 hr time points T3D Therapeutics, Inc. T3D-959 Preclinical Studies 7 AD Metabolic Events AD Structural Events AD Stress Events ↓ Insulin resistance ↓ IGF-1 resistance ↑ Reverse cholesterol transport ↓ Triglycerides ↑ HDL ↓ Ceramide Synthase 2 and SMPD3 (↓Ceramide) ↓ Aβ peptide ↓ pTau/Tau ratio ↓ GSK3β activation (↓ tau hyperphosphorylation) ↑ neuronal cell survival (in vitro) Reversal of neuronal cell loss Reversal of white matter atrophy ↓ Oxidative stress (histology) ↓ Inflammatory cytokines (TNFα, IL-1β) ↓ Ubiquitin (involved in protein misfolding – tangles/plaques) AD Cognitive Impairment Motor Function Impairment ↑ Spatial learning and memory, STZ rat, (also seen in APP/PS1 mice, Tg2576 mice & 3xTg-AD mice w/ other PPAR delta agonists) Anti-cachexia (↑ lean/fat mass ratio) Motor function improvement in STZ rat model • Multiple Type 2 Diabetes Models • AD model of sporadic AD – i.c. Streptozotocin (STZ) rat model ACTIVITIES RELATED TO AD T3D Therapeutics, Inc. T3D-959 Early Clinical Development 8  Healthy Volunteers (n=96) • Ascending single dose (QD): o safe and well tolerated up to 200mg; o no Maximum Tolerated Dose (MTD) reached. • Multiple ascending dose, 7-day (QD): o safe and well tolerated up to 200mg; o no drug-related AEs, o no SAEs, o no Maximum Tolerated Dose (MTD) reached • Pharmacokinetics: T1/2=20h, Tmax=3-4h. T3D Therapeutics, Inc. Phase 2a Exploratory Feasibility Study of T3D-959 in Mild to Moderate AD (T3D959-201) 9 Population 34 participants, 57-90 years, mild/mod. AD MMSE14-26 [17 mild MMSE 20-26, 17 moderate MMSE14-19] Concurrent AD Medications 28 of 34 ApoE4 genotype n=17 ApoE4 positive n=17 ApoE4 negative N Per Dose Per Group 3mg (n=8), 10mg (n=9), 30mg (n=9), 90mg (n=8) Dosing Once daily for 14-days Primary Objectives FDG-PET – relative brain glucose metabolism (CMRgl) BOLD fMRI – hippocampal functional connectivity (resting state default mode network) ADAS-cog11 DSST Plasma Metabolome Profiling Secondary Objectives Safety & Tolerability T3D Therapeutics, Inc. T3D959-201 10 Dose 3mg 10mg 30mg 90mg N 8 9 9 8 Age (avg.) 73.3 71.4 74.6 75.4 Sex M/F 4 / 4 4 / 5 4 / 5 4 / 4 MMSE (avg.) 19 19.9 21.9 18.8 ApoE4+/ApoE4- 3 / 5 7 / 2 4 / 5 3 / 5 T3D Therapeutics, Inc. T3D959-201: Pharmacokinetics 11 Single Point Plasma PK at approximate Tmax (3-4h post dosing at EOT) Consistent with Phase 1 Studies Potential Target Exposure, Assuming 35% Brain Penetration: ED50 multiples (X) PPAR delta PPAR gamma 3mg cohort 3.6X 0.3X 10mg cohort 12.0X 0.8X 30mg cohort 31.7X 2.0X 90mg cohort 114.9X 7.4X 3mg cohort – 86ng/ml = 195nM 10mg cohort – 290ng/ml = 654nM 30mg cohort – 763ng/ml = 1.72uM 90mg cohort – 2,766ng/ml = 6.24uM T3D Therapeutics, Inc. T3D959-201: Safety 12 Summary of Adverse Events (ITT Population) 3mg (N=9) 10mg (N=9) 30mg (N=10) 90mg (N=8) Subjects with at least 1 AE 2 (22%) 0 2 (20%) 0 Total Number of Events 3 0 5 0 Subjects with at least 1 SAE 0 0 0 0 Total Number of Events 0 0 0 0 Subjects with at least 1 Drug-Related AE 0 0 1 (10%) 0 Total Number of Events 0 0 1 0 Subjects with at least 1 Mild AE 2 (22%) 0 1 (10%) 0 Total Number of Events 2 0 0 0 Subjects with at least 1 Moderate AE 1 (11%) 0 2 (20%) 0 Total Number of Events 1 0 4 0 Subjects with at least 1 Severe AE 0 0 0 0 Total Number of Events 0 0 0 0 T3D Therapeutics, Inc. T3D959-201: Evidence of Peripheral Drug Activity 13 R² = 0.9486 -18 -13 -8 -3 2 7 0 10 20 30 40 50 60 70 80 90 100 Mean Change in FPG Baseline to End of Treatment (mg/dl) Dose (mg) Change in Fasting Plasma Glucose BL to EOT with Dose (mg/dl) T3D Therapeutics, Inc. T3D959-201: Evidence of Peripheral Drug Activity - Metabolomics 14 • Clinical Metabolomic data collection: ▫ Fasted Plasma samples collected at Baseline and End of Treatment for all dose groups ▫ Samples analyzed by Metabolon Inc. (Durham); Over 821 metabolites monitored • Analyses of Metabolomic Data: ▫ The 820 Metabolites analyzed and organized into eight super pathways and over one hundred sub-pathways ▫ Four Analyses Done: Dose Groups, Genotype, Gender and Responder (Dr Chris Newgard, Duke Molecular Physiology Inst.) • Key Observations: ▫ Lipid Metabolism effects observed with increasing dose  INCREASE in a wide array of fatty acid-derived acylcarnitine species. This profile is consistent with increased flux of fatty acids into the beta-oxidation pathway. ▫ Systemic Glucose Metabolism and Insulin Sensitivity changes with increasing dose  DECREASE in all three Branched Chain Amino Acids (BCAA) by higher doses of T3D-959. BCAAs are positively correlated with insulin resistance and diabetes T3D Therapeutics, Inc. T3D959-201: Evidence of Peripheral Drug Activity - Metabolomics 15 • Several species of ceramides are decreased by T3D-959 30 mg and 90 mg dose groups. • Ceramides have been implicated as mediators of insulin resistance and metabolic diseases Ceramides 3mg 10 mg 30 mg 90 mg ceramide (d16:1/24:1, d18:1/22:1) 1.13 0.95 0.71 0.84 ceramide (d18:1/14:0, d16:1/16:0) 1.1 1.05 0.86 0.77 ceramide (d18:1/17:0, d17:1/18:0) 1.03 1.12 0.91 0.84 ceramide (d18:1/20:0, d16:1/22:0, d20:1/18:0) 1.12 1.05 0.83 0.84 N-palmitoyl-sphingosine (d18:1/16:0) 1.06 1.02 0.89 0.89 N-stearoyl-sphingosine (d18:1/18:0) 1.05 0.98 0.82 0.82 ceramide (d18:2/24:1, d18:1/24:2) 1.08 0.96 0.92 0.99 Some of these are mixtures of ceramides Gr een means statistic ally signific ant (p=0 .0 5 ) dec r ease ceramide nomenclature: d18:1/14:0 the shingosine first and the N-acyl group second T3D Therapeutics, Inc. T3D959-201: Evidence of Peripheral Drug Activity - Metabolomics 16 • All three branched chain amino acids (BCAA), Leu, Ile and Val, along with related metabolites, are significantly decreased (p<0.05) in the 90 mg T3D-959 group. • BCAAs are positively correlated with insulin resistance and diabetes. Metabolite 3 mg 10 mg 30 mg 90 mg leucine 0.95 0.98 1 0.8 N-acetylleucine 0.98 1 0.91 0.82 isovalerylcarnitine (C5) 1.11 0.97 0.99 0.68 isoleucine 0.93 0.94 0.96 0.84 2-methylbutyrylcarnitine (C5) 0.99 1.02 0.96 0.81 valine 0.93 1.06 0.96 0.79 isobutyrylcarnitine (C4) 0.95 1.01 0.77 0.57 Green means statistically significant (p=0.05) decrease T3D Therapeutics, Inc. T3D959-201: Evidence of Peripheral Drug Activity - Metabolomics 17 • Genotype and Gender differences in T3D-959 Metabolomic Data • Long Chain Fatty acids increase with T3D-959 in E4 ‘High Dose’ subjects (30 mg and 90 mg) • Numbers are the ratio of metabolite EOT/BL. Red means p value is <0.05 Lipids - Long Chain FA Baseline All E4/E3 Low Dose E3 EOT/BL Low Dose E4 EOT/BL High Dose E3 EOT/BL High Dose E4 EOT/BL laurate (12:0) 1 1.1 0.9 0.83 1.58 5-dodecenoate (12:1n7) 0.99 1.26 0.79 0.94 1.72 myristate (14:0) 0.98 1.19 0.88 0.98 1.54 myristoleate (14:1n5) 1.03 1.2 1.01 1.08 2.23 palmitoleate (16:1n7) 0.81 1.24 0.91 1.38 2.42 nonadecanoate (19:0) 0.84 1.31 0.93 0.86 1.43 10-nonadecenoate (19:1n9) 0.87 1.48 0.9 0.89 1.92 eicosenoate (20:1) 0.9 1.33 0.9 0.98 1.79 stearidonate (18:4n3) 0.89 1.47 0.89 0.88 2.02 eicosapentaenoate (EPA; 20:5n3) 0.88 1.27 0.96 1.03 1.63 linolenate [alpha or gamma; (18:3n3 or 6)] 0.85 1.13 0.87 1.07 1.65 dihomo-linolenate (20:3n3 or n6) 0.92 1.31 0.82 1 1.34 docosapentaenoate (n6 DPA; 22:5n6) 0.93 1.28 0.88 0.97 1.45 dihomo-linoleate (20:2n6) 0.81 1.39 0.82 0.94 1.79 T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 18 METHODOLOGY Relative Brain Glucose Metabolism measured (not absolute) to reduce patient burden of multiple testing (∆ R CMRgl (EOT-BL)). Measured at baseline (BL) and at end of 14-day dosing (EOT). Analyses: 1. Exploratory voxel-wise (SPM) analysis of the whole brain to identify Regions of Statistically Significant Differences (ROSD) for ∆ R CMRgl (EOT – BL) with uncorrected p<0.005.. 2. Pre-defined Summary Indices: Addressing Type I error due to multiple regional comparisons. a) sROI Statistical Regions of Interest b) Four anatomical ROIs: pre-specified known AD-affected regions of interest (ROIs): 1) Posterior Cingulate (PC), 2) Precuneus (PreC), 3) Bilateral Middle Temporal Gyrus (BMTG), and 4) Right Inferior Parietal Lobule (RIPL) c) Hypometabolic convergence index (HCI) d) Longitudinal HCI (MCID) ∆ R CMRgl (EOT-BL) for four. 3. sROI Index and the longitudinal change in the sROI index (∆ sROI) T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 19 OBJECTIVES Primary Hypotheses Testing - Postulates 1. T3D-959, upon oral delivery, can penetrate the human blood brain barrier (as indicated from rat pharmacokinetic studies). 2. T3D-959’s will increase the regional cerebral metabolic rate for glucose (CMRgl) in the brain of AD patients (based on its mechanism of action as an insulin and IGF-1 sensitizer). 3. T3D-959-elicited changes in CMRgl in the brain of AD patients will exhibit a dose dependency. 4. T3D-959 will increase CMRgl, including in AD-vulnerable hypometabolic brain regions. Exploratory Hypotheses Testing - Postulates 5. T3D-959-elicited changes in CMRgl may be a potential biomarker of the drug’s ability to improve cognitive function. 6. ApoE4 carriers and ApoE4 non-carriers will exhibit different T3D-959-elicited changes in glucose metabolism. T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 20 DATA ANALYSIS – COMPLICATED BY T3D-959 MOA MOA: PPAR delta, ubiquitous expression in brain, regulator of glucose energy expenditure Changes in cerebral and cerebellar glucose metabolism anticipated after drug treatment. Issue: Ubiquitous expression of PPAR δ in the brain and a primary mechanism of action to improve insulin and IGF-1 resistance predicts that glucose metabolism in any Reference Region (RR) would also be affected by drug treatment. Resolution (partial): Two RR’s used and compared, Whole Brain (WB) and White Matter (WM) ∆ (RR) CMRgl is defined as the change in the ratio of ROI to Reference Region (EOT minus BL) T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 21 Whole Brain (WB) and White Matter (WM) Reference Regions Respond Differently to T3D-959 Positive ROSDs : Increased drug treatment-related, regional glucose metabolism greater than increased drug treatment-related, reference region glucose metabolism. Spatial extent of ROSD is greater when Whole Brain (WB) is used as reference region than when White Matter is RR Positive ∆ R (WB) CMRgl with 90 mg T3D-959 Positive ∆ R (WM) CMRgl with 90 mg T3D-959 Observations: • Regions with positive ROSDs -Portions of multiple brain bilateral regions including the Insula, Hippocampus, Vermis, and the Putamen • Positive ROSDs calculated with the different RRs are in similar brain regions, but differ in spatial extent of the ROSDs T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 22 Regions of Special Sensitivity to T3D-959 • Brain Regions with larger increases in glucose metabolism than the average Whole Brain • Positive ∆ R CMRgl (EOT – BL) values with Whole Brain as reference region • From overlay of voxel wise analysis and sROI analysis • Composite of all doses Observations: • Multiple Brain Regions with positive ∆ R CMRgl (EOT – BL) values relative to Whole Brain – p values listed • Greatest increase in ∆ R CMRgl (EOT – BL) observed with the two highest doses (30mg & 90mg) (data not shown) •Putamen shows largest dose dependent changes and survived Family Wide Error analysis Brain Regions ∆ R CMRgl (EOT-BL) P-value Orbital_front_intersection_L 0.03±0.04 3.0E-05 Orbital_front_L 0.01±0.05 1.9E-01 Orbital_front_ intersection _R 0.03±0.03 3.0E-05 Orbital_front_R 0.01±0.05 5.2E-01 Insula_ intersection _L 0.03±0.03 1.0E-6 Insula_L 0.02±0.03 1.1E-04 Insula_ intersection _R 0.03±0.04 2.0E-05 Insula_R 0.02±0.04 1.3E-03 Cingulum_Ant_ intersection _L 0.04±0.05 1.3E-04 Cingulum_Ant_L 0.03±0.04 5.2E-04 Cingulum_Ant_ intersection _R 0.03±0.04 1.9E-04 Cingulum_Ant_R 0.02±0.05 7.9E-03 Putamen_L_ intersection 0.06±0.06 1.0E-05 Putamen_L 0.05±0.07 5.0E-05 Putamen_R_ intersection 0.06±0.06 1.0E-05 Putamen_R 0.05±0.06 3.0E-05 T3D Therapeutics, Inc. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET 23 Evidence of Drug Exposure and Activity in the Brain Dose Dependent Increase in the Spatial Extent of Regions of Statistically Significant Change (ROSD) in Relative CMRgl (EOT-BL) Composite of Trial Subjects by dose group (n=8-9) Observations • Dose dependent changes observed in multiple FDG- PET Outcomes including voxel-wise analysis on left • Statistically Significant changes observed even at 3 mg dose (not shown) • Regional specificities observed – different regions respond to drug differently T3D Therapeutics, Inc. 24 T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET •Data from average Whole Brain voxel-wise analysis: •This data is evidence that the low dose (3 mg) dose gets into the brain and engages its target •We do not know if these are positive or negative ∆ R CMRgl values for carriers and non-carriers • A genotype difference in response to a low level of drug was observed as shown in this voxel-wise analysis • Colored region indicate where difference between ∆ R CMRglCarrier and ∆ R CMRglNC for each voxel reaches statistical significance (p<0.005) • At higher doses genotype-based differences disappear – no colored regions at the higher doses • Greater decline in ApoE4 carriers means: ∆ R CMRglCarrier < ∆ R CMRglNon-Carrier These observations are not simply a reflection of the difference in glucose metabolism between ApoE4 Carriers and Non-Carriers, since ∆ R CMRgl measures the change over the T3D-959 treatment period T3D Therapeutics, Inc. 25 Main Observations from Relative FDG-PET Clinical Neuroimaging Studies A) Apparent dose-dependent effect of T3D-959 on cerebral glucose metabolism. B) T3D-959 alters cerebral glucose metabolism even at the lowest 3 mg dose C) Reference regions (Whole Brain and White Matter) used to calculate regional relative changes in glucose metabolism, appear to be also affected by T3D-959. D) AD-affected, and AD-spared brain regions appear to respond equally to the two lower doses of T3D-959, but at the two higher doses, AD-affected regions, do not respond to drug as well as AD-spared brain regions such as brain white matter. E) Caveat: Interpretation of the FDG-PET results above is dependent on the use of two reference regions, multiple different doses and relative (not absolute) CMRgl data. The possibility that the observed increases/decreases of ∆ R CMRgl may be due to subtle effects on brain glucose metabolism not directly related to drug, can not be excluded. T3D959-201: Exploratory Neuroimaging Outcomes – FDG-PET T3D Therapeutics, Inc. T3D959-201: Exploratory Cognitive Outcomes – Digit Symbol Substitution Test (DSST) 26 Average Improvement at Followup Day 21 (all doses) Moderate Patients (MMSE=14-19) Mild Patients (MMSE=20-26) All 2.4 (+/-6.0) n=17 7.0 (+/-8.2) n=17 ApoE4- 1.7 (+/-4.8) n=11 8.0 (+/-4.7) n=6 ApoE4+ 4.4 (+/-7.6) n=6 6.5 (+/-9.6) n=11 T3D Therapeutics, Inc. T3D959-201: Exploratory Cognitive Outcomes – ADAS-cog11 27 All Subjects ApoE4+ Subjects ApoE4- Subjects n= 8 9 9 8 n= 3 7 4 3 n= 5 2 5 5 IMPROVEMENT WORSENING ApoE Genotype Influence on Cognitive Outcomes as Assessed by the ADAS-cog11 Test • Dose trend analysis – significant genotype effect p=0.004 • 10mg Cohort – skewed distribution of E4 positive subjects • All subjects E4+ and E4- improved with 30mg dose • All E4- subjects improved with 3, 10, 30mg doses • 90mg Cohort E4- subjects – 4 of 5 with moderate disease severity T3D Therapeutics, Inc. T3D959-202: Open Label Extension 4-Subjects who completed T3D959-201, dosed 18-22 weeks, 15mg QD 28 Safety • No AEs • No Safety Signals • No Tolerability Issues Cognitive Assessments • CIBIC+ group average = 2.75 (all at least minimally improved) • ADAS-cog11 Subjects – Demographics & Baseline Characteristics Subject Sex Age ApoE4 Genotype MMSE ADAS-cog11 DSST 3001 M 88 4/4 19 37.3 5 3003 M 70 w/4 18 40.0 3 3005 M 71 w/4 22 27.3 5 3014 M 71 w/4 25 14 38 T3D Therapeutics, Inc. T3D959: Clinical Development: In Progress 29 • Multi-kilogram Scale GMP Manufacturing of T3D-959 Drug Substance (API) Underway • 6-Month Rat Chronic Toxicology Study Underway • 9-Month Monkey Chronic Toxicology Study Underway • Preparing for Drug Product Campaign to support Phase 2b clinical trial • Preparing for radiolabeled synthesis of T3D-959 for GLP and GMP mass balance studies T3D Therapeutics, Inc. T3D959-203: Clinical Development - Future 30 Planned Phase 2b Study (Mild-to-Moderate AD) Screening Randomization 50/50 ApoE4+/ApoE4- T3D-959 High Dose (n=60) T3D-959 Medium Dose (n=60) T3D-959 Low Dose (n=60) Placebo (n=60) Baseline 12-Weeks 24-Weeks Co-Primary: ADAS-cog11, CDR-SB Secondary: ADCS-ADL, Verbal Fluency Exploratory: FDG-PET (subset of patients) T3D Therapeutics, Inc. Conclusions: T3D959-201 Phase 2a Outcomes 31 • New Chemical Entity T3D-959, a PPAR delta-selective agent is safe and well tolerated across all doses • Good systemic exposure in Phase 1 confirmed in Phase 2a • Metabolomics profile verifies expected systemic pharmacology consistent with improving insulin resistance • FDG-PET outcomes suggest dose-dependent brain penetration and expected pharmacology • Multiple signals of potential efficacy observed o Potential to improve cognitive outcomes o Potential ApoE4 genotype association with treatment outcomes (significant differences observed in; (a) plasma metabolome, (b) CMRgl & (c) ADAS-cog11) o Potential to change brain glucose metabolism • Results support continued evaluation in a Phase 2 RCT T3D Therapeutics, Inc. Acknowledgements: 32 Support • National Institute On Aging of the National Institutes of Health under Award Number R44AG049510 • North Carolina Biotechnology Center Neuroimaging Analyses • Banner Alzheimer’s Institute – Dr. Kewei Chen, Dr. Eric Reiman Metabolomics • Dr. Chris Newgard (Duke University Medical Center) • Metabolon, Inc. Clinical Trial Sites • New Hope Clinical Research, Charlotte, NC. - Dr. Santosh Gopalakrishanan • Miami Jewish Hospitals, Miami, FL. - Dr. Marc Agronin • Brain Matters Research, Delray Beach, FL. - Dr. Mark Brody .

The release as fetched from its publisher. t3dtherapeutics.com ↗