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Calico, As Expected, is Working on Low Yield Projects in Aging


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#1 reason

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Posted 24 February 2021 - 11:11 AM


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."

Link: https://www.calicola...inical-programs


View the full article at FightAging

#2 RvrseTheCrse

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Posted 13 May 2022 - 07:08 PM

Hi Guardian Reason,

 

I read the comments at the link at the bottom. What's the deal with the hate for Calico? The argument is they should be trying harder to come up with a drug that is universally capable of significantly altering, delaying the aging process over a targeted therapy for the CNS of ALS patients? Seems we're still some years away from the former, no?

 

Also, do you know the difference between ISRIB and the EIF2b activator in clinical trials with Calico?



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#3 Mind

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Posted 14 May 2022 - 09:57 AM

Hi Guardian Reason,

 

I read the comments at the link at the bottom. What's the deal with the hate for Calico? The argument is they should be trying harder to come up with a drug that is universally capable of significantly altering, delaying the aging process over a targeted therapy for the CNS of ALS patients? Seems we're still some years away from the former, no?

 

Also, do you know the difference between ISRIB and the EIF2b activator in clinical trials with Calico?

 

The original promoters of rejuvenation and unlimited lifespans, such as those who read Reason's blog and post here are striving for much greater things than Calico. Most are upset to see billions of dollars going into Calico that could have been spent on smaller efforts/start-ups more focused on rejuvenation. Calico "looks" like the beginnings of another big parma company that produces a marginally effective product with a long list of side effects - just effective enough to get government approval but not effective enough to move the needle very far on human life extension. Whatever they produce or license will also likely be incredibly expensive.


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