Not all the results from stapled peptides are as promising.In Nov., researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Parkville, Australia, in collaboration with scientists from Genentech in South San Francisco, California, tested a chem. reinforced peptide that, like Walensky′s drug, targeted BCL-2 proteins.Unexpectedly, the stapling actually destabilized the peptide in its normal protein state, so it couldn′t target and kill cells as well as hoped (ACS Chem. Biol. doi:10.1021/cb3005403, 2012).Joseph Yanchik, Aileron′s president and chief executive, remains unfazed by the findings. "To use the WEHI work as the basis for general conclusions about stapled peptides is a bit of a stretch," he says, noting that the study used a particular stapled peptide that Walensky′s group had previously intentionally weakened for structural experimentsGenentech′s parent company, Roche, doesn′t seem too concerned by the data coming from its subsidiary, either.In 2010, the Swiss pharmaceutical giant inked a deal with Aileron worth up to $1.1 billion, and last year the two partners started to present work stemming from the collaboration at scientific meetings.Most recently, in Dec., Lane and his colleagues showed that stapled peptides can successfully reach and reactivate a tumor-suppressor protein called p53 to block cancer cell growth (ACS Chem. Biol. doi:10.1021/cb3005148, 2012).The true test, of course, will come later this year when ALRN-5281 enters the clinic. "Promising results from the first series of clin. trials would serve to validate an entirely new therapeutic approach for treating human disease," Walensky says.