Establishing Preclinical Development Operations in China

1
Establishing Preclinical Development Operations
in China

• Ming Guo, Ph.D.
• VP Pharmaceutical Sciences Manufacturing
• SABPA Pacific Forum
• Nov. 4, 2006

2
Peer into the biotechnology industry's crystal
ball, and the shape you see might look a lot like
Ascenta Therapeutics

• Company is a model of efficiency for the drug
  development industry
• San Diego Union Tribune October 27, 2006

3
Ascenta Profile

• Private Oncology Development Company
• Founded in September 2003 in San Diego with IP
  from NCI U. Michigan
• Now with gt40 employees in San Diego, Shanghai and
  Philadelphia
• Expert, efficient economical oncology business
  model
• Ascenta team is highly experienced in oncology
  drug development
• Early discovery is generated externally via
  academic alliances
• Preclinical pipeline is progressed in a
  wholly-owned Shanghai subsidiary
• Clinical trial enrolment optimized by US
  bicoastal site management organization
• Ascentas apoptosis pipeline is rapidly advancing
  and highly competitive
• Product pipeline focused on Bcl-2, MDM2 and XIAP
  apoptosis targets
• AT-101 is an oral pan-Bcl-2 inhibitor
• AT-201 is an oral inhibitor of MDM2 entering
  Phase 1 in 2Q07
• AT-301 is an inhibitor of XIAP entering Phase 1
  in 2H07
• Clinical Lead AT-101 is an oral pan-Bcl-2
  Inhibitor
• The only oral pan-Bcl-2 inhibitor in clinical
  trials (entering Phase 3 in 2Q07)
• Single-agent clinical activity seen in first 3
  tumors tested in Phase 2

4
Ascentas Global Reach and Efficient
Discovery-Development EDGE
Discovery Alliance with Shaomeng Wang, PhD
University of Michigan 30 chemists biologists
San Diego Headquarters Manages discovery
alliances, all IND-enabling preclinical
development West Coast clinical operations
Ascenta Shanghai RD Ctr A Wholly-owned
subsidiary 15 FTEs, Chemists Biologists All
data transferred to San Diego nightly via Ascenta
internet portal
Philadelphia Site Management Office Manages all
clinical trial sites in East Mid-West
5
Ascenta Shanghai

• Wholly-owned subsidiary
• WOFE status essential for success
• Inventions owned by Ascenta
• Secure data infrastructure with warehousing in US
• Bilingual oversight from US and Shanghai
• Chemistry Capabilities
• Key intermediate Synthesis
• API batch scale-up (10-100 gram)
• Analytical and formulation development
• Formulation and stability testing
• Biology Capabilities
• In vitro and in vivo screening
• Rodent and non-rodent PK coordinated with local
  Shanghai contractors
• DMPK and tox assessments

Ascenta Shanghai
6
Ascenta Shanghai Laboratory
7
Future Plans

• To continue to build the preclinical function
• Chemistry and Discovery Manufacturing lab for
  synthesis of key intermediates, scale-up of lead
  compounds, formulation and process development
• In Vivo efficacy screening models
• DMPK Studies
• Screening Toxicology
• IND enabling studies following US GLP and ICH
  guidelines
• IND Filing with SFDA in China
• IND Filing in Hong Kong and US
• Clinical trials
• Proof of concept trials
• Part of Phase 3 multi-national trials
• Registry trials for China market

8
Challenges

• Acceptance by Regulatory agencies is uncertain
• The first to file will be scrutinized
• While the situation is improving, it will have to
  be closely watched
• Patent protection improving but still a risk
• IP law and related judicial practices are in the
  early stages of development
• Clinical Development is less advanced than
  preclinical
• A physical presence is necessary to realize
  benefits
• Working through US CROs decreases the
  cost-savings
• Close supervision will be essential to realize
  cost-savings quality