Strategic business proposal targeting CRISPR/Cas9 as a potential therapeutic and investment target for the treatment of Huntington's Disease

1. CRISPR
as a potential treatment for
Huntington’s Disease
Team #6
Melody Cho
Nikhil Penugonda
Tony Lee
Karan Sheth

2. Executive Summary
Problem
No curable treatment for
Huntington’s disease
Solution
CRISPR genome editing to
reduce transcription
Advantage
Permanent removal of mutated
gene eradicating disease
Market Size
150,000 patients at risk of
developing Huntington’s disease
every year
Business Strategy
Partner with CRISPR technologies
for groundbreaking development
Future Growth
Introduction of MNTK method for
genetic neurodegenerative diseases

3. Huntington’s Disease
Huntington’s disease is an inherited
disease that causes the progressive
dying off, or degeneration, of nerve
cells in certain parts of the brain.
The disease, which gets
progressively worse, attacks motor
control regions of the brain, as well
as other areas.
Medication like Tetrabenazine is
available to modulate
neurotransmitters, however there is
no treatment to cure this disease.

4. Treatments Comparison
Symptom Management
Treatment
Immunotherapy RNAi CRISPR
Overview
Medications available to
modulate neurotransmitters
Activation of immune
system to fight mHTT
mRNA degradation to
reduce translation
Genome editing to
reduce transcription
Pros
-Easily available
-Covered by insurance
-Slows down symptoms
-Targets only immune
system so less side
effects
-Immune system learns
to fight degenerating
cells
- Potentially curative
-Single treatment -
provides sustained
HTT reduction
-Permanent removal of
genetic cause
-Highly specific and
targeted
-Cost effective
-Easy to design
Cons
-Does not cure the disease
-Costly over a long period of time
-Causes depletion of dopamine
leading to depression
- Revs up immune
system with side effects
including flu
- Does not work on all
patients
-Immune system can
attack other healthy
organs
-Irreversible with
unknown risk -
Does not distribute
well into brain tissue -
Requires long term,
continuous expression
-Early developmental
stage
-Irreversible
-Ethical concerns with
germline manipulation
-Unexpected off
targeting mutations

5. Why use CRISPR to treat HD?
● CRISPR/Cas9 specificity: HD is a disease with
genetic anticipation, only curing the root
cause in DNA can completely eliminate the
disease
● CRISPR/Cas9 has higher target specificity,
lower off-target effects than RNAi
● Potential variation in strategies

6. Two Methods of CRISPR in treating HD
Image source: Laboratory of Neurotherapies
and Neuromodulation (LNCM), Neuroscience
Research Center (CRN)Lausanne University
Hospital (CHUV)LausanneSwitzerland
AAV9 (Adeno-associated virus) 9 is a
typical delivery channel

7. Blood Brain Barrier Issue
● Most AAVs cannot easily cross from the
bloodstream into the brain, they are
blocked by brain capillaries cells that
form the blood-brain barrier
● Some studies have shown promise that
AAV9 can transport CRISPR/Cas9
through this barrier
● This method has much potential as a lot of
other genetic neurodegenerative disease
have similar pain-point

8. Business Strategy
Collaborate
Budget
Price
Market
Leverage

9. Collaborate
CRISPR Therapeutics
● Multiple CRISPR related therapies in their pipeline
● CRISPR Therapeutics does not currently operate in the
Neurodegenerative space
● Had a four year, $105M partnership with Vertex
Pharmaceuticals
Partnership
● Sun God Pharmaceuticals gains access to CRISPR Therapeutics’
gene editing technologies
● CRISPR Therapeutics provides market and clinical trial
knowledge
● SGP granted exclusive rights to first drug developed through the
partnership

10. Budget
$3 Billion Budget
CRISPR Therapeutics Partnership: $500 Million
Payroll: $50 Million
Initiating Clinical Trials: $450 Million
Research & Development: $2 Billion

11. Price therapeutic based on core considerations*
Price: $125,000 per treatment
Value Cost Ethics
*Assumptions made with U.S market in mind

12. Price therapeutic based on core considerations
Value
Average estimated $1M spent over 20 years on disease management , eventually
resulting in death.
87.5% cost reduction for patients and HMOs, in addition to a priceless, disease-
free life.
Priced at $125,000 per patient for a one-time, curative treatment...

13. Price therapeutic based on core considerations
Cost
- 150,000 market size (at risk patients)
- Projected payback period: 5 years post-
launch
- Significant projected profitability
scaling with increased trust and
precedence
Year Market
Penetration
(%)
Market
Capture
Aggregate
Revenue
1 1 1500 $187.5M
2 2 3000 $375M
3 4 6000 $750M
4 8 12,000 $1.3B
5 16 24,000 $3B
6 32 48,000 $6B
7 64 96,000 $12B
8 80 120,000 $15B

14. Price therapeutic based on core considerations
Ethics (looking forward)
Outcome Based Reimbursement
Work with HMOs and KOLs to develop
criteria and establish payments based
on patient well-being.
Government Subsidies
Engage with the government to
discuss possibilities of subsidizing a
first-mover, high-benefit therapeutic
Risk Mitigation with Reinsurance
Work with HMOs to mitigate
company risk and ensure timely
investment recovery.

15. Market drug collaboratively
Pre-launch
● Engage with Key Opinion Leaders (KOLs) and HMOs during
clinical development to build trust
● Promote education of benefits and viability
Post-launch
● Work continuously with health care organizations for post-
treatment monitoring and care
● Demonstrate efficacy in U.S market before introducing globally

16. Leverage the MNTK Delivery System for innovation
Capabilities achieved:
● Platform for drug delivery across blood
brain barrier
● Viable gene-editing CRISPR/Cas9
mechanism within the CNS
6M
The Future:
Positioning SGP to disrupt the genetic neurodegenerative disease space
with revolutionary gene editing technology
Market Size of Prevalent Genetic CNS
Diseases w/o Cure
1M
150,000

17. Conclusion
● Current treatments for Huntington’s Disease only address the symptoms
● CRISPR technology represents the best balance of risk & reward
● Exciting potential of the MNTK Delivery System
● Collaboration with CRISPR Therapeutics
● Ethical considerations of curing Huntington’s Disease
● Price and Market strategy
● Leveraging MNTK for the future

18. Questions?
Problem
No curable treatment for
Huntington’s disease
Solution
CRISPR genome editing to
reduce transcription
Advantage
Permanent removal of mutated
gene eradicating disease
Market Size
150,000 patients at risk of
developing Huntington’s disease
every year
Business Strategy
Partner with CRISPR technologies
for groundbreaking development
Future Growth
Introduction of MNTK method for
genetic neurodegenerative diseases