GlobeImmune
presentation for Globeimmune... they seem to be concentrating on a particular IL28b genotype
Discussion
The discovery of the IL-28 B genotypes (Ge et al., 2009) and their predictive value for spontaneous
clearance of HCV (Thomas et al., 2009) and response to pegIFN/ribavirin therapy (Ge et al. 2009) are
significant breakthroughs in the understanding of the molecular biology of HCV. The role of IL-28 B
variants in acute clearance of HCV strongly suggests that it is a marker of the immune capacity of the
patient, and influences response to interferon therapy based on the immune differences in the IL-28 B
subgroups. IL-28 B testing in GI-5005-02 showed excellent balance between the GI-5005 triple therapy
and SOC groups. Furthermore, important differences were noted for the different IL-28 B genotypes
related to the timing and magnitude of viral clearance and SVR. GI-5005 triple therapy improved end
of treatment viral clearance in all IL-28 B genotypes (C/C; 84% vs 76%, C/T; 69% vs 54%, T/T; 60%
vs 20%) and improved SVR in the C/C (74% vs 65%) and T/T groups (60% vs 0%).
The pattern of response in the C/T group suggests an important role for response guided therapy due
to the fact that an advantage of 15% in response was observed at end of treatment but not at 6 months
post-treatment. The majority of GI-5005 treated C/T patients who relapsed in the post-treatment period
cleared HCV virus after 12 weeks of therapy, suggesting that they would have benefited by a lengthened
duration of treatment. The greatest favorable treatment effect for GI-5005 was observed in the T/T group
with an advantage in end of treatment viral clearance of 40% and an advantage in SVR of 60%. This
may reflect an immune deficiency inherent in the T/T group, and suggests that GI-5005 can stimulate
HCV specific immunity in a manner that compensates for this deficit.
Differentiated therapeutic vaccine platform
Advanced portfolio of clinical products
GI-5005: completed phase 2 in HCV
GI-4000: multiple phase 2 trials in Ras mutated cancers
$150 million invested capital
$500+ million Celgene oncology alliance
Tarmogen® platform
Targeted molecular immunogen
Recombinant S. cerevisiae expressing target proteins
Selectively activates T cells
WW IP through mid-2020s
Tarmogen pipeline
Immune response matters in HCV
Natural history
20% acutely exposed clear without treatment
80% of acutely exposed progress to chronic infection
6 to 9 months of consolidation required after viral negativity
Hepatic clearance requires immune response
Anti-virals including IFNs suppress replication but do not enhance hepatic clearance
IL-28 B SNP > clearance and IFN response
GI-5005
GI-5005-02 phase 2 design
Demographics
End of treatment response (ETR)
Sustained virologic response / naïve
IL28B predicts response to IFN therapy
T/T genotype disproportionately represented in AAs
Viral clearance by IL-28 B genotype
ALT normalization at end of treatment
Safety summary
Commercial launch time line
Tarmogen products
Celgene alliance
Exclusive option to all oncology Tarmogens
Economics
$40 million up-front
$10 million in equity
$30 million in R&D funding
In excess of $500 million in milestones
Double digit royalties
GlobeImmune runs development
Alliance governed by joint development committee
Targeting mutated Ras
Unmet medical need
Ras-mutation related cancers ~170,000/year in the US
Ras mutation+ CRC (~40%) resistant to EGFR MAbs
Ras mutation+ NSCLC (~25%) resistant to chemo/TKIs
Primary biology of pancreas cancer (>90% Ras+)
Un-druggable target
GI-4000?immunologic elimination of mutated cells
GI-4000 series targets mutated Ras
GI-4000 program
Randomized Phase 2b in pancreas cancer
Adjuvant study in resected pancreas cancer
Up to 200 patients
Survival data ~YE 2010
Phase 2a in NSCLC (MSK)
Consolidation therapy following successful first-line treatment for Stage I-III Ras-mediated NSCLC
24 patients
Complete enrollment ~YE 2010
First colorectal trial starts Q2 - 2010
2010 milestones
GI-5005-02 final data AASLD
Non-responders
Immunology
GI-5005 pivotal program
Commercial manufacturing process
Expansion of T/T subgroup
End of phase 2 meeting
GI-4000
GI-4000-02 pancreas early data ~ YE
GI-4000-03 NSCLC – immunology and safety data
