JDRF PowerPoint Presentation 2

SmartCells, Inc. 1

SmartCells, Inc.

Todd C. Zion, Ph.D.

Co-founder, President & CEO

April 6th, 2009

e-mail: [email protected]

Phone: 978.927.4246

Web: www.smartinsulin.com

An Introduction to SmartInsulinTM

SmartCells, Inc. 2

Imagine a “Smart” Insulin

• Once-a-day injection

• No hypoglycemia

• Near-perfect glucose control

• Significantly fewer finger-sticks

• Minimal dietary restrictions

Calculate Insulin Dose

Blood Glucose

Measure Food

SmartInsulinTM

Blood Glucose

Food

SmartCells, Inc. 3

SmartCells, Inc. and the SmartInsulinTM Mission

• Founded in August 2003

– Exclusive licensee from M.I.T.

– Based on founder’s 5+ years of Ph.D. research

• World-class collaborators to complement 12 full-time employees

– Management includes founder, M.I.T. Ph.D.’s, and biotech executives

– Collaborators from M.G.H., Joslin, former Lilly/Novo experts

• $4.2M+ in private investment; $6.3M+ in public grant funds

Corporate Headquarters in Beverly, MA (25 miles north of Boston)

For more information, please visit www.smartinsulin.com

SmartCells, Inc. 4

Insulin and Type 1 Diabetes

• Insulin saves lives, BUT with…

– Life-threatening bouts of hypoglycemia

– Poor glucose control and long-term complications

– Frequent finger sticks and counting carbs

– Constant vigilance

• Insulin lowers blood glucose levels no matter what

– Too much: Hypoglycemia

– Too little: Hyperglycemia and ketoacidosis

• Effective control requires glucose-responsive delivery

SmartCells, Inc. 5

-cell glucose-stimulated insulin release

• Provide the missing -cells: regeneration or transplantation

• Mimic the -cell function

Negligible below 100 mg/dl

Rapid increase between

100 and 400 mg/dl

Saturated maximum

above 400 mg/dl

http://journals.prous.com/journals/dot/20033904/html/dt390287/images/Langin_f1.gif Cerasi, E., Q. Rev. Biophys. 8 (1975) 1-41.

SmartCells, Inc. 6

The artificial pancreas approach

• SmartCells makes the insulin molecule glucose-responsive

• Eliminates the need for cells, pumps, sensors and algorithms

Assume the insulin

molecule cannot be

changed

Renard, E., Curr. Opin. Pharmacol. 2 (2002) 708-716.

Better algorithms and

device integration

Better accuracy,

redundancy,

biocompatibility

SmartCells, Inc. 7

1. IPC and GBM combine to form insoluble network

2. Free glucose molecules displace the IPC from the GBM

3. The matrix erodes from the surface inward

4. The released IPC lowers glucose levels in the body

5. The matrix stops eroding until the next glucose challenge

Glucose-responsive SmartInsulin technology

Insulin

Insulin

Insulin

Glycosylated

insulin-polymer

conjugate (IPC)

Glucose

Multivalent

glucose-binding

molecule (GBM)

Key:

Conceptual

particle surface

boundary

SmartCells, Inc. 8

SmartInsulin subcutaneous injection

Dispersion in 10 ml

multi-dose vial

Withdrawal into 31G

subcutaneous insulin syringe

SmartCells, Inc. 9

100

200

300

400

500

600

700

800

0 100 200 300 400

Time (min)

Seru

m R

at

Insu

lin

Co

nc.

(pM

)

0

100

200

300

400

500

Glu

co

se (

mg

/dl)

Insulin

Glucose

0

1000

2000

3000

4000

5000

6000

7000

8000

0 100 200 300 400

Time (min)

Seru

m I

PC

Co

nc.

(pM

)

0

100

200

300

400

500

Glu

co

se (

mg

/dl)

Insulin

Glucose

Pancreas-like performance in rats

SmartInsulin Pancreas

IP glucose IP glucose

• Glucose-stimulated release mimics pancreas

• Glucose stimulated to basal release ~ 4x-5x

SmartCells, Inc. 10

0

100

200

300

400

500

600

0 200 400 600

Time (min)

Glu

co

se

(m

g/d

l)

Diabetics

Normals

NO FEEDING

0

100

200

300

400

500

600

0 200 400 600

Time (min)

Glu

co

se

(m

g/d

l)

Diabetics

Normals

NO FEEDING

0

100

200

300

400

500

600

0 200 400 600

Time (min)

Glu

co

se

(m

g/d

l)

Diabetics

Normals

NO FEEDING

No hypoglycemia over 4x dose increase

• Substantially improved therapeutic

window vs. conventional insulin

• Minimal risk of dangerous

overdose

5 U/kg 10 U/kg

20 U/kg

SmartCells, Inc. 11

Safety summary in preclinical models

• No signs of injection site irritation

• No risk of hypoglycemia over broad range of doses

• No excessive body weight gain or loss due to repeated dosing

• No signs of organ abnormalities due to repeated dosing

• No signs of toxicity or cell abnormalities after repeated dosing

• No signs of anti-insulin antibody formation

SmartCells, Inc. 12

JDRF partnership summary

• Industry Discovery & Development Partnership

– Metabolic Control – Dr. Aaron Kowalski

• Initiated in August 2008

• Year 1: Pre-clinical formulation optimization in Type 1 models

– Successful completion of Q1-Q3 milestones

– End of Year 1: Success in large animal, human-representative models

• Year 2: Manufacturing and Safety Studies to Support Clinical Trial

– End of Year 2: Human Clinical Trials

SmartCells, Inc. 13

Animal Studies

Serum half-life in rats, cats and pigs

Safety Studies

Single dose ADME 14 day toxAntigenicityReceptor binding

Contract CROs

Toxicology Safety pharmacol

Study reporting

Manufacturing

Contract CMO Optimize process

Qualify suppliers Select assays Produce 1st

batch

Clinical batches Fill and finish Stability test

Stability test CMC reporting

Regulatory Request pre-IND meeting

Hold Pre-IND meeting

Design Phase 1 Contract CRO

Submit IND Active IND

Q2 ‘09 Q4 ‘09 Q1 ’10Q3 ‘09

Path to Proof-of-Concept Human Clinical Trial

Q2 ’10

Complete

Phase 1a

Clinical

Trial