Milestones awards

JessicaYoon

We are considering milestone awards at the ends of Round A (for teams that qualify to register their clinical trails) and Round B (for teams that qualify to conduct their clinical trials; learn more about the phases of the competition here).

Round A milestone awards might go to cover the expenses of submitting a proposal to the FDA or equivalent regulatory body.

Round B milestone awards might go to cover the expenses of the clinical trial.

Do you think such milestone awards are needed? Are there other milestone awards we should consider? How big should these awards be?

NickOttens

@Steve_Liebich, @techspeaker, @Navonica, can I ask your feedback on milestone awards for the Age Reversal competition?

We're considering milestone awards for teams that a) qualify to register their clinical trials, and b) quality to have their trials carried out.

Does that seem appropriate to you? How big should such awards be? Are there other milestone awards we should consider?

Also check out the proposed rounds of the competition here.

NickOttens

@RickyM, @siimsaare, you may also have insight on this question.

Once teams competing in an age reversal XPRIZE have qualified to register their clinical trial, and then to carry out their trial, how much money should we give them in the form of milestone awards to ensure everyone can participate in the competition?

NickOttens

Our thinking about milestone awards has changed.

Since we want the prize to be more open-ended, with teams possibly registering one or several years into the competition, teams won't be progressing at a similar pace.

Instead, we're thinking of milestone awards for teams that are the first to get their clinical trials approved in a certain category.

For example: gene therapy, or epigenetic reprogramming, or stem cells, or repurposed drugs.

An additional benefit would be that each milestone award could be funded by a different sponsor. A company that has an interest in gene therapy could sponsor a, say, $1 million gene-therapy milestone award. An individual with a particular interest in epigenetic reprogramming could sponsor a $500,000 milestone award in that category.

Our questions for you:

• Which categories should we consider?
• Could milestone awards in different categories differ? We ideally want to incentivize audacious treatments, so a milestone award for, say, gene therapy might be higher than one for repurposed drugs. (This would, of course, also depend on how much money sponsors are willing to put it.)

Other thoughts are welcome too! @goya, @markjayct, @pscheck, @danbelsky, @mario_perez, @Umbertog, @amoskalev, @Wally, please let us know what you think!

NickOttens

@stepha51, @DavidGiampaolo, @bschurman, @Shiza, @ThomasS04, @lbratkovich, @stepha51, as investors, entrepreneurs, and marketing strategists, I'd like to ask your take on this, since it also goes to fundraising and marketing for an age reversal XPRIZE - what do you think would be valuable milestone awards?

mario_perez

Could milestone awards in different categories differ?

I think so. And I believe the focus should be on innovative treatments instead of repurposed drugs.

Those treatments that target the primary hallmarks of aging (genomic instability, telomere shortening, epigenetic alterations & loss of proteostasis) need to have a higher priority than drugs that target some downstream effects (e.g. metformin). That's my feeling.

p.s. I'm biased with reversing telomere shortening as the best candidate which influences the other primary hallmarks.

NickOttens

Thank you for your comment, @mario_perez! We agree we want to incentivize audacious, innovative treatments, so the milestone awards for the first teams to get their clinical trials approved in those categories may be higher.

@Muslim_Chechenov, @Longevity_Analytics, @GuyBahat, @mharte, @CraigM, @dave, and @sruiz, I'd love to get your perspective on this from an investor/fundraising perspective. We're thinking different milestone awards could be funded by different sponsors. For example, an investment fund with a particular interest in gene therapy could fund a $1 million gene therapy milestone award. A pharma company with an interest in repurposed drugs could fund a $500,000 milestone award. Etc.

Do you like that idea?

Which companies, organizations, and individuals do you think may be interested in funding such milestone awards?

Categories could include:

• Stem-cell transplantation
• Genetic engineering & gene therapy
• Epigenetic reprogramming
• Nano-robotics

DidierC

Hello,
Sorry, maybe I'm saying something wrong since I had no time to understand all aspects of the competition. But I think one important milestone would be to demonstrate lifespan of mice considerably exceeding the normal lifespan.
Didier

NickOttens

Thanks for your comment, @DidierC! However, we decided against including animal experiments in the competition and only incentivize the development of rejuvenation treatments for humans.

DidierC

OK, thks for the fast feedback!

NickOttens

@jewhitson, @grahampawelec, @marky, would love your input on this as well. What do you think about our plan for milestone awards in an age reversal competition?

jewhitson

@NickOttens I think that milestone awards are a great idea. Age reversal is going to be a marathon, not a sprint. It's extremely unlikely that any "magic bullet" will be discovered given the complexity of the aging process in humans. This means that progress is going to be very incremental and rewarding each step along that path is going to be a more successful venture than just providing a reward for a very long term goal. I also agree with @DidierC that adding a mouse milestone would be a good idea. I understand the desire to focus just on human studies but the fact of the matter is that no rejuvenation treatment is going to go to clinical trials without first being demonstrated to work in mice. If the lifespan of a mouse could be say doubled, it would be a massive leap forward for the field of geroscience. If you want to reward people along each leg of this marathon, it's worth including.

mario_perez

@jewhitson from what I know that has already been shown by Maria Blasco's group. In fact, they are now moving into clinical trials in humans for curing pulmonary fibrosis:
https://www.cnio.es/en/news/publications/paved-the-way-for-future-gene-therapy-pulmonary-fibrosis-associated-with-ageing/

jewhitson

@mario_perez Thanks for sharing! However, it seems that they have only demonstrated a potential method to cure an age-related disease, rather than actually reversing aging or extending lifespan in the mouse model. There are lots of studies in mice to treat age-related diseases and, while I acknowledge the importance of them, I agree that it doesn't make to have an award for them in this context. However, a demonstrated method to dramatically increase lifespan in mice would be a big step forward and something that no one has yet done.

mario_perez

@jewhitson you're welcome! Although they proved that extending lifespan was possible:

Finally, telomerase-treated mice, both at 1-year and at 2-year of age, had an increase in median lifespan of 24 and 13%, respectively.

https://pubmed.ncbi.nlm.nih.gov/22585399/

One injection was enough for the proof of concept. I guess if they had more injections the lifespan would have increased more.

They're focusing on age-related diseases because you can't just do clinical trials for reversing aging. Once you understand aging though, it's possible to intervene in those diseases.

jewhitson

@mario_perez Oh for sure, it's great work and the increase in median lifespan is significant, but it's not the dramatic increase in lifespan I am talking about. Many different treatments have been shown to increase median lifespan modestly in the same 10-25% range in mice. However, something that could increase maximal lifespan by 100% or more in mice has never been demonstrated and would be far more significant for coming up with a way to slow aging.

NickOttens

It's still on the table, but our thinking is that age reversal may very well be achieved in mice in the next few years without an XPRIZE, so it wouldn't be audacious enough for a milestone award. Especially when we're thinking the competition could take anywhere between 5 and 10 years.

mario_perez

@jewhitson @NickOttens I feel animal experimentation shouldn't be the focus of the competition. Rising that number to 100% won't necessarily translate to the same number in humans. In my opinion, there's been enough proof that aging is malleable. There are way too many age-related diseases and we should start to tackle them.