Slide 1: Biotech Showcase, San Francisco, January 12-14, 2015
THERAPEUTICS. Development, aS bi CAPSTONE & Lipimetif’ Biotech Showcase San Francisco, CA January 12 -— 14, 2015 Confidential
Slide 2: Safe Harbor Statement
Safe Harbor Statement Statements in this presentation or otherwise attributable to Capstone regarding our business that are not historical facts are forward looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking s
Slide 3: AEM-28 Cardiovascular Program Summary
AEM — 28 Cardiovascular Program Summary Clinical: “Phase 2 Asset — Statistically Significant in Lipid Reduction Regulatory: “Targeting Homozygous Familial Hypercholesterolemia (HoFH) and Orphan Indications > CMC: “Inexpensive, Solid-Phase Synthesis with Proprietary Formulation IP > IP: «New, 21 Year
Slide 4: AEM-28 is Derived from Native Apo E
AEM-28 is Derived from Native Apo E AEM-28 (Ac-hE18A-NH,)} is a 28-amino acid peptide constructed from 2-domains of native Apo E "Hinge region’ WISI jor lipid-binding region (CO,H-terminal AEM-28 ‘Adapted from Hatters et al., Trends Biochem Sci. 2006; 31(8):445-54 Apo E researched since 1960's Prove
Slide 5: AEM-28 Target Indication: Homozygous Familial Hypercholesterolemia
AEM-28 Target Indication Homozygous Familial Hypercholesterolemia (HOFH) Homozygous Familial Hypercholesterolemia (HoFH) CHAP REMEES zor Vv Rare genetic disease (= 12,000 worldwide) » Homozygous (both parents) bear offspring with no LDL receptors on liver: No clearance of LDL Cholesterol » Blood oft
Slide 6: Advantages of Apo E Mimetics in HoFH
Advantages of Apo E Mimetics in HoFH > Rapid (one hour) and dramatic lipid reduction > Does not inhibit natural regulatory pathways > ApoE protective effect on arterial walls lessens atheroma burden > New proprietary formulation for acceptable safety/tolerability > Mechanism allows synergy with stat
Slide 7: AEM-28 Target Indication: HoFH Preclinical Evidence
AEM-28 Target Indication HoFH Preclinical Evidence > Watanabe Heritable Hyperlipidemic (WHHL) rabbits have same genetic defect as human FH patients — complete absence of LDL receptors > WHHL rabbits are refractory to statins, bile acid sequestrants, PCSK9 inhibitors, etc. > Single dose @ 7.5 mg/kg o
Slide 8: Pre-Clinical Efficacy
Pre-Clinical Efficacy AEM-28: Athero Preclinical Beneficial Duration of Effect Representative en face Lesions in face Lesion Area (n=13 in each group) Control AEM-28 AEM-28 Sustained Effect on Atherosclerotic Lesion Regression in Fat-fed APO E Null Mice 4 Weeks After Stopping Drug Treatment Poster P
Slide 9: Dose Response and Cholesterol Exposure Curve
Dose Response and Cholesterol Exposure Curve AEM-28 in Cynomolgus Monkeys (Wake Forest) Cummulative 7-Day Decrease in Cholesterol in Normocholesterolemic (NC) Change in Total Cholesterol in and Hypercholesterolemic (HC) Monkeys (mg/dL*hr) Hypercholesterolemic Cynomolgus Monkeys at 3, 6, and 12 mg/kg
Slide 10: AEM-28 Regulatory Strategy
AEM-28 Regulatory Strategy Clear and Rapid Path to HoFH Approval > Regulatory approval path for orphan indication in US and EU established by Juxtapid™ (Aegerion) and Kynamro™ (Sanofi/Genzyme) >» Cholesterol reduction (biomarker) approvable endpoint in this population / no “clinical outcomes” endpoi
Slide 11: AEM-28 Phase 1a;1b/2a Top Line Findings
AEM-28 Phase 1a;1b/2a Top Line Findings Single site hospital-based clinic in Australia n= 51 testing IV doses with intra-cohort control Fasted Normal Healthy Volunteers / Elevated Fasting Triglycerides with High BMI / Refractory Hypercholesterolemics (all with elevated cholesterol) Standard pre-medi
Slide 12: Phase 1a Pharmacodynamic Results
Phase 1a Pharmacodynamic Results: Escalating Dose Response Curve VLDL Chotestera! Tigiyeerides ‘AEM2@ minus Placebo es Bu i ‘AEM.28 minus Placebo i ———— o il | ic ial | i a i 3 3 } cag Fal ] i 2 | | ie 5. | i ‘ 2 otis) i slsnecs ste * Statistically significant results favoring the 2mg and 3.54mg dos
Slide 13: Phase 1b/2a Trial Results
Phase 1b/2a Trial Results Triglycerides: Comparison of Minit ional C i VLDL: ci : Comparison of MinimumFractional Concentrations ‘versus Pre-Dose Observed In First 12 Hours Post-Dose, verus Pre-Dose Observed in First 12 Hours Post-Dose ones) (Mean # SEM) g8 ag BE §3 EN i 38 st Bs 83 83 Ea BS ¢ & ge
Slide 14: New AEM-28-02 (Analog) Formulation
New AEM-28-02 (Analog) Formulation Targets Orphan Indications in Hyperlipidemia Type la Type 1b Type3 Types 4 and 5 Familial Decreased Chylomicron Hyperchylomicronemia LPL remnants 1 in 1,000,000 = 300 or LPL Lipase Deficiency Familial apoprotein Altered Chylomicron/ Cl deficiency Apo C2 VLDL 1 in 2
Slide 15: Pharmacoeconomic Case Study: Acute Hypertriglyceridemic Pancreatitis
Pharmacoeconomic Case Study: Acute Hypertriglyceridemic Pancreatitis * TG > 1,000 + ICU /Acute Hospitalization + Genetic Origin + Prescribed Therapy: “No Fat Diet / + 5% Mortality Fibrates / Prayer” * 6,000 Hospital Subjects - Avg 5 Day ICU Stay @ $30K/Day $150K + Avg 5 Day Acute Stay @ $12K/Day $ 6
Slide 16: New AEM-28-02 formulation: Future Target Indications
New AEM-28-02 formulation Future Target Indications Acute Coronary Syndrome Clinical Atherosclerosis 1,300,000 Hospital (ACS) Outcomes Peripheral Artery Disease Clinical Intimal Hyperplasia/ 600,000 Hospital and (PAD) Outcomes Atherosclerosis Infusion Clinic High Risk Metabolic Clinical VLDL/Triglyc
Slide 17: AEM-28-02 Potential Therapeutic Role
AEM-28-02 Potential Therapeutic Role Acute Coronary Syndrome Therapy ACS ene ! Gitta Gere. Stabilization/Maintenance 1 ' 200 1 1 1480 1 1 Non-HDL-C 1160, 1 Annual AEM-28-02 Follow Up (Not Based on Cinical Data = High ACS Recurrence in Three Months Post Event * Particularly problematic in diabetes an
Slide 18: Summary
Summary > New, but Historically Proven Apo-E Class of Lipid Lowering Drugs > Targeting HoFH, Acute Hypertriglyceridemic Pancreatitis and Other Orphan Hyperlipidemic Indications > Potential to Reduce Atherosclerosis > AEM-28 Phase 1a;1b/2a Study Met Objectives > Analogs of AEM-28 (21 Year Patent Life
Slide 19: LipimetiX Development contact details
Lipime Development, LipimetiX Development, LLC 5 Commonwealth Road, Suite 2A Natick, MA 01760 Dennis Goldberg, PhD. 508-651-3715 dgoldberg@lipimetix.com Jock Holliman 602-286-5586 jholliman@capstonethx.com Lipimetig >)