REGULATORY Considerations for early stage Life Science Startups Leslie Williams - IMMUSANT Jenny Freeman - Respiratory Motion

1. 1
Regulatory Considerations
Leslie J Williams
ImmusanT, Inc • One Kendall Square, Suite B2004 • Cambridge, MA 02139Confidential & Proprietary – Not For Distribution

2. 1. 2February 25, 2016 Confidential & Proprietary – Not For Distribution
Who Am I?
• Leslie J Williams: Founder, Director, President & CEO ImmusanT
• 25+ years industry experience
• Early Stage Start-Up Experience: Advisor and Co-Founder &
CEO multiple companies
• Ventaira Pharmaceuticals – President & CEO
• INO Therapeutics (Ikaria) – Management
• Big Pharma experience – Merck, GSK
• Device/Equipment – Ohmeda
• Venture Capital: Venture Partner – Battelle Ventures
• Business Advisor and Mentor
• Education: MBA, Washington University; BS, Biology/Nursing,
University of Iowa

3. 1. 3February 25, 2016 Confidential & Proprietary – Not For Distribution
Business Planning Considerations
Sector Device
(drug delivery,
implanted, valves,
monitoring; etc)
Diagnostic Therapeutic
(drugs, vaccines,
biologics)
Some drug delivery
Healthcare IT / Services
IP Yes - FTO YES Patent Life Important
10 years to develop
Countries
Know How
Design / Method
Regulatory PMA/510K Companion?
510K/PMA; CLIA
IND, BLA
(Fast track; Breakthrough)
HIPAA
Stark Law
Prototype/
Demonstration
√√√√ (seeing is
believing)
Depends on diagnostic No √√√ demonstration – talk
to end user
Animal Data YES YES MUST N/A
Publication Important Important MUST N/A
Scale Up Manufacturer ?
GMP
Manufacturer? GMP CMC – manufacturing
GMP
Must have or clear path
Reimbursement Current or new CPT HCPCS
Comparative Effectiveness
YES Federal and State
Distribution Think through – alone
or partner; countries
Important – Central Labs Think through - alone or
partner; by
Countries
Must have
Launch/Market trajectory US/EU/ROW Adoption - uptake US/EU/ROW Adoption - uptake

4. 1. 4February 25, 2016 Confidential & Proprietary – Not For Distribution
Drug Development Process – Cost/Time
Preclinical Clinical Approval Market
Toxicology Investigational New
Drug Application
Phase I Phase II Phase III New Drug
Application
Phase IV /
Postmarket
surveillance
safety safety dosing
efficacy
safety efficacy
side effects
Expenses $15.2 million $23.4 million $86.5 million
Time 21.6 months 25.7 months 30.5 months
1 to 6 years 6 to 11 years 0.6 to 2 years 11 to 14 years
Overall probability of success
30% 14% 9% 8%
Conditional probability of success
40% 75% 48% 64% 90%
Sources: Dimasi, Hansen, and Grabowski (2003).
Notes: The line marked “Overall probability of success” is the unconditional probability of reaching a
given stage. For example, 30 percent of drugs make it to phase I testing. The line marked
“Conditional probability of success” shows the probability of advancing to the next stage of the
process conditional on reaching a given stage. For example, the probability of advancing to Phase III
testing conditional on starting Phase II testing is 48 percent.

5. 1. 5February 25, 2016 Confidential & Proprietary – Not For Distribution
Be Realistic About Development/Regulatory Path

6. 1. 6February 25, 2016 Confidential & Proprietary – Not For Distribution
Regulatory
• Major Factor in Success and Funding
• Moving target
• Planning and execution is critical
• Obtain credible expertise
• Avoid landmines
• Know the challenges
• Define risk mitigation strategy
• Expect the unexpected
• Identify Path:
• Therapeutic, device, diagnostic, IT
- IND, BLA, PMA, 510(k)

7. 1. 7February 25, 2016 Confidential & Proprietary – Not For Distribution
• Have you had a pre-IND meeting?
• Path forward?
• Did the FDA identify any concerns or risks?
• If the path is IND/BLA is there precedent? If diagnostic is this PMA,
510(k), what is the predicate? Traditional or Novel?
• TPP; Indications for use? Aligns with business plan or
reimbursement strategy?
• Primary endpoints in the study? Will it support reimbursement?
Early adoption?
• Timeline for US approval? Global Strategy?
• Names of Legal Counsel, Regulatory Experts
Typical VC Questions
7

8. 1. 8February 25, 2016 Confidential & Proprietary – Not For Distribution
General Guidelines: Regulatory
1. Understand your desired path to approval
2. Understand accelerated pathways and appropriateness for your product
3. Hire an expert (consultant)
4. Communicate with the FDA early and often if possible
- look for guidance documents
5. Understand and research the division at the FDA that will be
responsible for your product
6. Know as much about your product as possible (safety; mechanism)
7. Don’t short cut critical aspects of development– go slow to go fast
8. Budget appropriately (time & money)
9. MITIGATE RISK wherever possible
Regulatory….without a strategy, you won’t get funded

9. 1. 9February 25, 2016 Confidential & Proprietary – Not For Distribution
Regulatory Considerations & Precedence
Monitor the development pathways and hurdles of similar
products in pivotal trial and close to marketing
•Circassia ToleroMune (synthetic peptide) cat allergy vaccine
development
–Successfully completed P-II study (Feb 2011)
–Developed regulatory pathway with authorities/agencies*
•Allergy Therapeutics Pollinex Quattro seasonal allergy vaccine
– FDA clinical holds to be lifted with revised IND protocols
– MAA submitted to Germany PEI and will pursue EU
registration expansion using EU-MRP+