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 >40 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 Ascenta’s 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 –Synergy seen in combinations with other oral targeted agents & biologics

4 Early Discovery Generated Externally Optimization & Manufacturing Early Preclinical Late Preclinical & Clinical Development Ascenta’s Global Reach and Efficient Discovery-Development EDGE San Diego Headquarters Manages discovery alliances, all IND-enabling preclinical development & West Coast clinical operations Ascenta Shanghai R&D 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 Discovery Alliance with Shaomeng Wang, PhD University of Michigan 30+ chemists & biologists

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 ( 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