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

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."



Lack of ambition, waste of money. Calico will disappear in a few years when they will see first real therapies in the market far surpass their "best" lab results. There will be no point to pursue modest results when people will add 10 years of life routinely.

Posted by: Jonathan Weaver at February 24th, 2021 5:39 AM

If they manage to deliver a substantial treatment for ALS it still would be an achievement. It is ironic since calico was founded by Ray Kurzweil who subscribers to the ideas if LEV and has written a series of books of the technological progress. On the other hand Google is known for losing interest in the projects in a year or two. From this perspective it is a miracle that they didn't cancel calico yet..

Posted by: Cuberat at February 24th, 2021 6:17 AM

@Cuberat: "It is ironic since calico was founded by Ray Kurzweil"

My same thought. On the other hand, after shouting wildly optimistic previsions for decades, RK has been very silent during the past few years.
Did he tire, sell out, or lose hope in a speedy solution to the problem?
I wonder...

Posted by: Barbara T. at February 24th, 2021 7:57 AM

I never expected much from Calico from the get go. I saw it as a recycled version of Larry Ellison's foundation, which has also accomplished zilch. Ray Kurzweil was never a bio-engineering guy. He always saw the future in terms of Drexlerian nanotech and AI. This is why I never placed much value in his predictions. I suspect one of the problems with Calico is their reliance on the "advice" of conventional medical researchers.

Posted by: Abelard Lindsey at February 24th, 2021 9:37 AM

I'm a programmed aging guy as opposed to Reason's damage theory. But on Calico, we totally agree. I practically shed tears on the enormous waste of money.

Posted by: Wayne Johnson at February 24th, 2021 1:19 PM

@Wayne Johnson The programmed aging theory have been proven wrong in animal models. Removing damage in animals showed that they rejuvenated. Periodic application of the therapies in animals should keep them young as long as we want, we just need functional therapies for the 7 types of damage, not just one as of 2021 (senolytics).

Posted by: Jonathan Weaver at February 24th, 2021 2:27 PM

The mistake of Brin and Page with Calico is the same than that of Ellison with his foundation, and the mistake that Musk didn't make with SpaceX and Tesla. They are all computer entrepreneurs that, after becoming rich, tried a different technology field. Musk didn't only put his money into SpaceX, he put himself into it. He read a lot, asked a lot, trained himself a lot, and became a decent astronautical engineer, even if he doesn't have a formal degree. He knows pretty well all his rockets and participated in the design of all of them. Brin, Page and Ellison didn't do that with gerontology. They simply put money to hire experts. That's why their projects became business as usual, a copy of the NIA, so they achieved the same than the NIA.

Posted by: Antonio at February 24th, 2021 3:39 PM

@Wayne Johnson
>I'm a programmed aging guy
I have seen too often programming code evolving far from the intelligent design. Once i have witnessed a bug cancelling another bug. Like a mutation undoing another mutation.

Having said that, I think that there will be little difference whether the aging is programmed or just a side effect. It won't be a nice switch with a simple configuration and timer to expire amenable to point genetic editing. Rather it would be something duplicated imperfectly all over the place with implied dependencies. And since the nature doesn't have human type of intelligence for us it would be as good as semi-chaos.

Posted by: Cuberat at February 24th, 2021 4:05 PM

@Antonio I agree, they only care about money, whatever the fields, even those they didn't care at first. Musk don't care much about money, he only want to disrupt fields. The bad news is that Musk already said he won't try to invest/disrupt the anti-aging field, because of his personal moral about it. Neuralink isn't much about rejuvenating, it has a health component but we all know the real goal is human/computer interface. Curing neurologic disorders is just a side-effect, a bonus. Musk will be a trillionaire in 2030 or before thanks to starlink but he won't even give a single billion to SENS. That's really frustrating.

Posted by: Jonathan Weaver at February 24th, 2021 4:11 PM

@Barbara T
He was hired as the head of AI research at Google. he is busy creating the super intelligence that will magically find the solution . Probably he cannot make public statements without consulting with a bunch of lawyers. Besides his predictions were overly optimistic. He still almost comically claims they are "essentially" correct.

Posted by: Cuberat at February 24th, 2021 4:13 PM

@Cuberat: Haha! Perfectly summarised.

Posted by: Barbara T. at February 24th, 2021 4:57 PM

@Jonathan Weaver: Why doesn't Musk support anti-aging? I mean, what's his moral objection??
I actually thought that what he was really angling for with Neuralink was digital immortality. Eventually, at least.

Posted by: Barbara T. at February 24th, 2021 5:02 PM

@Jonathan Weaver: Yeah, I know. We need a different entrepreneur. Also, he is probably too busy with SpaceX and Tesla already and will be so for quite some time. We need a new Musk in the medical field, somebody that can not only invest in radical life extension but also make drug development much much cheaper (including, of course, the cost of clinical trials).

Posted by: Antonio at February 24th, 2021 5:19 PM

I recently had the opportunity to spend time with two researchers from Calico -

Dr. Rochelle Buffenstein -

Dr. Adam Freund -

I disagree with the general "Monday morning quarterback" assessment here

First, these are competent people working on valid longevity science - maybe not SENS stuff, but important work nonetheless

Second, whether giving that billion $$ to Aubrey, or Sinclair, or Mike West, or anyone else in longevity biotech who you wish had it, is debatable based on clinical failures in all of their "wakes"

But thirdly, and most importantly, a modest, late stage, clinical success, connected to the Abbvie / Former Genentech eco-system, connected in some context to "healthy aging", will yield 1,000X the downstream public awareness / pr benefit to support the whole fledgling field, than any other pipeline program

I suggest stop being so obsessed with what Calico has done wrong in your eyes pharamcologically, and start rooting for their success...

Posted by: Ira Pastor at February 25th, 2021 4:17 AM

To be fair solving aging is nothing like building cheaper and better rockets, like Musk has been doing. Basically all the rocket tech already existed, it just needed some refinement and the addition of advanced computerised landing capability. Not to say it was easy, but if solving aging just required an extremely driven entrepreneur, we would not still be sitting here with various arguments over the best approach or even the underlying cause of aging after the best part of 20 years.

I do think aging is tractable and will be solved, most likely in time for many of us. But it isn't the same as Space X or Tesla.

Posted by: Mark at February 26th, 2021 8:58 AM

SENS and Calico have both been financial suporters of Irina and Mike Conboy at Berkeley, so they have some points of convergence. I also remember reading that Calico was investing in the work of Maria Blasco on telomere therapies

Posted by: Jose A at February 28th, 2021 10:26 AM

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