Company Analysis - Celldex & Avant
A robust combined pipeline
A current analysis of Avant's pipeline (Graph 1) shows it to be at a relatively healthy early-to-mid stage, with five products in preclinical development and 6 in clinical development up to Phase II. The exception to this is Rotarix, a novel two-dose oral vaccine against the G1P, G3P, G4P and G9P strains of rotavirus. Developed in collaboration with GlaxoSmithKline, which has exclusive worldwide marketing and development rights, Rotarix already boasts launches in several markets including Australia, Ireland, Mexico and Thailand, as well as approvals in over 90 countries worldwide including within the EU. Rotarix is currently under review by the US Food and Drug Administration, with a response expected in the second half of 2008.
Further down the pipeline, Avant has several projects at Phase II, including CholeraGarde, a live, geneticallyattenuated single-dose oral vaccine against cholera which has already generated positive clinical results. In a Phase II trial in Bangladesh, the vaccine was well tolerated, and gave a favourable immune response in >70% of adults tested. In children aged 9mth-5yr, CholeraGarde 200 million cfu produced a protective immune response in 77%. Also in development is Ty- 800, another single-dose oral vaccine, in this case against Salmonella typhi, the cause of typhoid fever. Avant has received Phase I and II grants from the US National Institute of Allergy and Infectious Diseases and the vaccine is currently in a Phase II trial in 180 adult volunteers to evaluate safety, reactivity and immunogenicity, with results expected in the first half of 2008. In a previous Phase II trial, Ty-800 was found to be well tolerated, and was immunogenic over a wide range of doses.
At the preclinical stage, Avant has a variety of products under investigation, including vaccines against Escherichia Coli, Shigella and Campylobacter infection.
In terms of development status, Celldex brings a very similarly-weighted, if somewhat earlier-stage, pipeline to the table (Graph 2), with 5 preclinical projects ongoing and 4 in clinical trials. However, breaking down the pipeline by indication shows a very different focus from Avant, particularly with regard to Celldex' efforts in oncology and chronic viral infection. This variety will give the new company a greatly diversified portfolio (Graph 3), undoubtedly an important base on which to build for the future.
In testament to the importance of Celldex' APC targeting technology, two of these pipeline candidates are derived from this platform. CDX-1307 is a fusion protein-based vaccine incorporating a mannose receptor-specific MAb conjugated to the ß-chain of human chorionic gonadotrophin (hCG) and designed to induce CTL responses in patients with ßhCG-expressing tumours. Phase I trials in colorectal, pancreatic or bladder cancers have already yielded positive results, with Phase I trials in breast cancer also underway. CDX- 240 is another APC-based vaccine, under development for HIV prophylaxis, which is expected to enter Phase I trials in 2008.
Crucially, Celldex also brings the newly-formed Avant's leading product, CDX-110. This peptide vaccine targets the naturally-occurring mutant epidermal growth factor receptor (EGFR) vIII, a functional variant of epidermal growth factor. In a Phase IIa trial in 23 patients with primary glioblastoma multiforme, CDX-110 administered with granulocyte macrophage colony-stimulating factor demonstrated minimal toxicity without evidence of autoimmunity, and generated both humoural and cellular responses against the EGFRvIII peptide. CDX- 110 is now in a Phase II/III trial for this indication.
