1.
Therapeutic Targeting of
Alzheimer's Disease with a
Selective Antibody
August 28, 2020

2.
What is the problem?
Desperate need for
Alzheimer’s disease
(AD) therapeutics
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease
• AD is 100% fatal
• No approved disease-modifying treatments
• Current drugs only treat the symptoms of
dementia
– Oral regulators of acetylcholine (Aricept) or
glutamate (Namenda)

3.
What is the problem?
Protein aggregation is at the core of AD
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease
• Accumulation of aggregated
amyloid-beta protein (Aβ)
• Aβ senile plaques, oligomers
and protofibrils
Brain slice from AD patient
Selkoe, Trends Cell Biol, 1998, 8, 447
Bitan et al., PNAS, 2003, 100, 330

4.
How does product/service solve problem?
Our solution is mAbSL antibody
• Amyloid-β protein (Aβ) monoclonal antibody
• We have obtained, cloned, sequenced, expressed,
purified and characterized the monoclonal antibody
– selectively targets a
protofibril form of Aβ
– given to early-stage AD
patients
– passive immunization
treatment for AD
Goure et al., Alzheimers Res Ther, 2014, 6, 42
mAbSL + +++ +
(aducanumab)
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

5.
How does product/service solve problem?
More on selectivity differences
A42, ng/well
0 20 40 60 80
A450nm
0
1
2
protofibrils
monomers
fibrils
ng
A42, ng/well
0 20 40 60 80
A450nm
0
1
2
3
protofibrils
monomers
A B C(BAN2401)
selective mAbSL113 non-selective mAbSL513
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

6.
What is the market use?
How will mAbSL be delivered?
• Clinical diagnosis of early stage AD
– mild cognitive impairment (MCI) and mild AD
• In-patient intravenous delivery of monoclonal
antibody solution
• Monthly infusions
• Measurement of cognitive improvement

7.
What is the market use?
Commercial
potential of an
AD therapy
Early-stage AD (US)
10M MCI/mild cases
$100M 1st year sales
(10% of market)
$1B after 5 years
(market & case growth)

8.
What competition exists?
Drug
Short-term
dementia
relief
Stops AD
progression
Reverses
AD effects
Antibody
selectivity
Cholinesterase
inhibitors
Glutamate
regulators
Inflammation
Tau
Amyloid (Aβ)
Aducanumab
BAN2401
mAbSL
Current
trials
Approved
&
prescribed
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

9.
What is the status of the intellectual property?
• AMYLOID-BETA ANTIBODIES
– University of Missouri-St. Louis
– Patent application 62/889,220 (Filing date 8/20/2019)
– Composition of Matter and Methods claims
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

10.
What is the stage of development?
• Cloned and obtained the variable region
DNA sequences for multiple selective and
non-selective mAbSL antibodies
• Developed methods for expression and
purification of mAbSL antibodies
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

11.
Potential regulatory path for mAbSL
• New Drug to pursue expedited Fast Track review
• Clinical Trials, 5-7 years, early-stage AD, will seek pharma
partnership
– Phase 1 (safety, tolerability, immunogenicity,
pharmacodynamics, pharmacokinetics), 50-100
participants
– Phase 2 (clinical efficacy), 500-1000 participants
– Phase 3 (efficacy, long-term safety, tolerability 1000-1500
participants
• No approved comparable for AD
• Average price for monoclonal antibody treatment is $96,000
(prices for oncology and hematology mAbs much higher)
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease

12.
What is needed for further development?
Research Milestones
• Further research is needed to strengthen case that monoclonal
AbSL antibody (mAbSL) is a potential AD disease-modifier
1. mAbSL production scale-up ($50K)
2. mAbSL effect in AD transgenic mice ($200K)
a. diagnostics ability of mAbSL in control-treated AD mice
b. prevention of pathology in mAbSL-treated AD mice (young)
c. reversal of pathology in mAbSL-treated AD mice (aged)
3. humanize mAbSL antibody ($50K)
AD Antibody – Passive Immunization Treatment for Alzheimer's Disease