Calico represents a sizable investment in research and development related to aging and age-related disease. Unfortunately, all the signs have pointed towards this effort going into projects that cannot possibly do more than very modestly affect aging. The publicity materials here further confirm this view of their strategy. They are not targeting the underlying damage that causes aging, but rather manipulating stress response mechanisms in order to try to tinker the aged metabolism into a state that is slightly more resilient to that damage. Upregulation of stress responses, as illustrated by the practice of calorie restriction, can have interesting effects on life span in short-lived species, but does comparatively little for longevity in longer-lived species such as humans. This is not the path to meaningfully large outcomes. It will not change the world, the shape of a life, the late stages of decline, to a great enough degree to matter.
Calico Life Sciences and AbbVie today announced clinical-stage programs in two areas - immuno-oncology and neurodegeneration, currently in Phase I studies. In addition, the companies are advancing a strong pipeline of novel targets that includes more than 20 active programs in discovery or preclinical development in age-related diseases. The lead Calico immuno-oncology program is focused on PTPN2 inhibitors which act at multiple steps in the cancer immunity cycle. There are two molecules currently in Phase I development, ABBV-CLS-579 and ABBV-CLS-484, both of which are novel, orally bioavailable PTPN2 inhibitors. The two molecules are being developed by Calico in collaboration with AbbVie.
The lead Calico neurodegeneration molecule (ABBV-CLS-7262) is an eIF2B activator which targets a key regulator of the highly conserved integrated stress response pathway. Inhibition of this pathway has therapeutic potential in a number of neurodegenerative diseases, such as ALS, Parkinson's disease, and traumatic brain injury. ABBV-CLS-7262 is currently in Phase I studies with plans to begin a study later this year in patients with ALS. "We believe that at the root of every great advance in medicine is a deep understanding of the biology that underlies a specific disease pathway. The quest for this depth of understanding has been our primary focus at Calico in the areas of aging and age-related diseases. Our approach requires patience, perseverance and great collaboration both internally and with external partners such as AbbVie and the Broad Institute, who not only share the same philosophy, but are able to execute upon it."