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Replies to post #211343 on Biotech Values
For those tracking R&D productivity metrics, antibodies have been a real outperformer: based on a comprehensive data review of clinical success rates, antibody (mAb) programs were found to have a likelihood of approval at IND filing 2x higher than conventional small molecule NCEs (14.1% versus 7.6%, respectively). Further, non-oncology mAbs were even more likely to succeed, exhibiting a 19.3% probability of going from IND to market.
While these metrics are great, and reflect some of their intrinsic, natural advantages as therapeutic agents, there’s still considerable rates of failure: 80-85% of mAbs are discontinued during development. Recent failures of Oncomed’s demcizumab (and earlier tarextumab and vantictumab) and Astrazeneca’s tralokinumab Phase III asthma trial are just the latest examples, and highlight the challenge of drug R&D with any modality. And even once they are approved, failures can continue happen – like Roche’s unexpected failure with Tecentriq in bladder cancer this week.
To frame the mAb landscape, a quick background on the various mAb frameworks is warranted. Early mAb therapeutics were derived from mouse immunizations, which led to the first approved agent, muromonab-CD3 (OKT3). As “foreign” to humans, these murine antibodies were highly immunogenic, leading to anti-drug antibodies (called human anti-mouse antibodies, or HAMA) that neutralize the mAb and prevent it from working effectively. The quest to reduce a mAb’s immunogenicity by relying on increasing amounts of human antibody sequences became an important vector in the field’s evolution since the 1980s. Chimeric antibodies, which use mouse variable domains and human constant regions, were a step forward, but these too are typically immunogenic.
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