jdrf powerpoint presentation 2
TRANSCRIPT
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