S5E29｜重金押注抗衰老公司，硅谷真的可以做出长生不老药吗？
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碰撞 世界， 生动活泼。 嗨 大家好， 我是 科技 早知道 的 节目 监制 刘灿。 今年 9月麻省理工 科技 评论 报道， 亚马逊 创始人 贝佐斯 已于 近期 投资 了 专注 于 抗衰 方向 的 生物科技 公司 L S 这是 一家 今年 4月才 成立 的 致力于 推动 重 编程技术 的 抗衰老 公司。 科研 团队 包括 2012年 诺贝尔奖 获得者、 诱导性 多功能 干细胞 知名 研究 学者 山中 声明， 在 尚未 有 任何 产品 诞生 的 情况下， got to slap 在 今年 的 上半年 已经 吸引 了 至少 2.7亿美元 的 投资。 投资者 的 名单 还有 另外 一位 硅谷 的 亿万富豪 尤里 米尔纳。 事实上 这 已经 不是 硅谷 富豪 们 第一次 入局 抗衰 领域 了。 早 在 2018年， 贝佐斯 就和 十 人 陪 跑 的 联合 创始人 彼得 蒂尔 共同 投资 了 E D D biotechnology。 这是 一家 最早 实现 靶向 清除 衰老 细胞 药物 商业化 落地， 并在 2018年 成功 上市 的 公司。

如果我们 要 继续 追诉 硅谷 富豪 投身 抗衰老 领域 的 故事， 其实 还 可以 从 2013年 谷歌 创始人 的 李 佩奇 宣布 10亿美元 投资 calle 启动 抗衰 研究 项目 开始 讲 起。 我们 有 理由 相信， 在 颠覆 互联网、 物流、 制造、 航空航天 等 领域 之后， 硅谷 的 下一个 目标 就是 通过 生物工程 技术 实现 人类 长生不老 的 梦想。 本期 节目 我们 邀请 到了 同样 在 抗衰 领域 被 视为 明星 公司 的 硅谷 新贵 古 dian 的 首席 科学 官 Martin walsh Johnson。 Martin son 在 硅谷 湾区 知名 的 巴克 衰老 研究所 从事 衰老 领域 的 研究 工作。 他 和 主播、 导演 一起 讨论 了 硅谷 富豪 们 投资 l lives 等 生物科技 公司 背后 的 原因 是什么， 他们 在 关注 哪些 技术， 又将 向 哪些 方向 继续 发展， 这些 技术 最终 将 通过 什么 途径 实现 商业化 落地？ 最 重要 的 是， 人类 真的 可以 突破 目前 120岁 左右 的 寿命 上限， 实现 想 活多久 就 活多久 这样 听起来 不可思议 的 目标 吗？

由于 本期 节目 是 英文 节目， 这里 我 先 为 大家 总结 一下 本期 节目 的 精彩 亮点， 希望 这 能够 帮助 大家 更好 的 理解 本期 内容。 节目 中 Martin 首先 介绍 了 衰老 领域 的 研究 发展 历程。 他 从 科学家 tom Johnson 80年代 通过 对 蠕虫 基因 的 研究所 绘制 出的 人类 历史上 第一个 长寿 基因图谱 开始 讲 起， 论述 了 衰老 是 如何 在 短短 近 二十多年 成为 一门 单独 的 学科。 他 强调， 由于 衰老 涵盖 多种 疾病 和 技术 领域， 目前 的 头部 抗衰 公司 主要 都是 各自 专注 在 干预 或者 是 治疗 与 衰老 密切相关 的 一些 疾病， 就 比如 阿尔茨海默症、 眼病、 关节炎、 糖尿病、 癌症 等等。 这个 赛道 受到 大家 关注 的 玩家， 除了 近期 大热 的 alto slaps， 还有 老牌 的 明星 公司， 比如 city about telloh 和 以及 A I 驱动 的 insurance medicine， 还有 平台 型 的 初创 公司 比如 audio 和 gero stay alpha。

当 大家 问起 主流 的 抗衰 技术 都有 哪些 时， Martin 介绍 道， 目前 有 常见于 免疫治疗 的 雷帕霉素 靶 蛋白 抑制剂， 也就是 M2 抑制剂 和 常见于 糖尿病 防控 的 二甲双胍 靶向 抗衰老 治疗 技术， 俗称 T A M E， 在 抗衰 领域 里面 用 的 比较 多。 当然， 随着 更多 的 抗衰 领域 的 新发现， 包括 干细胞、 重 编程技术、 靶向 杀伤 衰老 细胞 的 小分子 药物 C O latics 也 逐渐 受到 了 研究 人员 和 投资 机构 的 更多 关注。 就 目前 已经 面市 的 抗衰 药品 而言， Martin 提醒 我们的 像 elsa health 所 推出 的 basis， 这种 产品 更 多是 定 位于 N A D 加 N M N 类 的 膳食 营养 补充剂。 它是 没有 经过 F D A 的 药物 监管 流程， 所以 产品 的 抗衰 效果 其实 有待 长期 观察。

在 讨论 这 一波 的 投资 热潮 时， 马丁 也 提到 他的 观察。 他 认为 不仅仅是 富豪 们 的 家族 信托基金 对 长寿 抗衰 领域 表现 出了 极大 的 热情， 还有 像 legibility vision fund 这种 长期 的 专注 于 抗衰 领域 的 细分 V C 以及 on dressing horses H V C 这种 头部 的 风险投资 人和 投资 机构， 都 对 长寿 抗衰 领域 表现 出了 极大 的 参与 热情。 当 被问 到 如何 去 看待 这个 赛道 的 超长 投资 周期 时， Martin 认为 虽然 这个 领域 大部分 的 投资 要 等到 产品 面世 后 才能够 获得 回报， 但 一般来说， 只要 实验 进入 到 二期 或者 三期 的 临床试验 阶段， 早期 的 风险 投资者 就可以 看到 比较 好的 投资 回报 了。 马里 也 认为， 目前 二级 市场上 unity cobo A G X 这种 抗衰老 的 概念 的 公司 之所以 出现 股价 低迷 的 状况， 是因为 二级 市场 的 投资者 他 更 关注 药物 实验 失败 对 公司 收入 的 负面影响。 但 其实 药物 在 二期 或者 是 三期 的 临床实验 中 出现 失败 是 很 常见 的 状况。 当然了， margin 也 提到 为了 规避 单一 药物 研发 失败 所 带来 的 商业 风险。 像 郭 立 恩 这样 关注 抗衰 技术 整体 路径 优化 和 成本控制 的 平台 型 公司， 在 商业模式 上 确实 会给 投资者 争取 到 更 低 的 边际 风险。

在 探讨 到 素有 硅谷 最 神秘 的 生物科技 公司 charle 的 发展前景 时， 马林 认为， 各家 公司 在 基础 基础上 的 研究 是 共通 的， 主要是 看 谁 能够 更好、 更 早 地 把 产品 落地。 事实上， mary 提到， 目前 抗衰 领域 最大 的 挑战 就是 弄清楚 衰老 的 机制， 理解 具有 衰老 表征 的 疾病 和 衰老 本身 的 因果关系 是 一项 浩大 的 工程， 如果 能够 发现 更多 的 衰老 标志物， 研究 人员 就可以 加速 生物 衰老 领域 的 量化 研究 能力， 真正意义 上 及时 有效 的 干预 衰老 的 过程。 因此， 像 古典 这样的 公司 就 设立 了 自己的 研究 奖学金 项目， 鼓励 更多 学者 关注 衰老 标志物。 如果 收听 我们 节目 的 小伙伴 中， 有人 正在 领 工作， 也 欢迎 大家 踊跃 尝试。 申请 的 链接 我们 已经 放在 了 本期 的 show note 节目 的 最后， 法院 邀请 Martin 分享 一些 个人 的 养生 秘诀。 Martin 非常 真诚 的 表示， 只要 规律 作息， 健康 饮食， 戒烟 戒酒， 加强锻炼， 我们 每个 人都 可以 做到 离 长寿 更 近 一步。 当然 他 也 提到 了 间歇性 断食 这种 方法， 不过 这个 因人而异， 如果 有 收听 节目 的 小伙伴 想要 尝试， 记得 先 咨询 医生。

除此之外， 在 本期 节目 中 大家 还会 听到 拥有 巴克 研究所 的 西海岸， 是否 比 东海岸 在 生物技术 领域 上 更 高一筹？ 长生不老药 L Z M 的 basis 试用 测评 到底 好 还是 不好， 以及 bio villa 的 C E O 伊丽莎白 帕 什 在 自己 身上 尝试 抗衰 药剂， 这样的 极端 例子 在 业界 是否 常见 等等 有趣 的 讨论。 另外 在上 一期 邀请 tiger graph 的 慧 松 讨论 图 数据库 的 节目 播出 后， 也有 小伙伴 在 评论 区 提到 他们 对 图 数据库 的 概念 和 案例 还有 很多 想 进一步 了解 的 地方。

10月20日 tiger graph 牵头 举办 的 graph 在 AI2021 中国 线上 峰会， 或许 能够 给 大家 带来 更多 的 启发。 大会 的 报名 链接 可以在 上期 的 生动 词 里 找到， 有 需要 的 小伙伴 记得 及时 点击 链接 报名 参与。 好的， 我的 介绍 就 到 这里 了。 接下来 就请 大家 在 打印 和 Martin 的 交谈 中， 一起 探索 长生不老药 的 真实 面貌。

Hello 大家好， 我是 丁 叫， 欢迎 收听 全 新一集 what next 科技 早知道。

Lady basis invest in anti aging company called auto slab, a company that is presumed biological reprogramme technology, a way to rejuvenate cells. Actually, IT is not the first time bases investing and thi aging tech companies, tech billionaire, a long tradition investing entire aging drugs, teg supplement or ever hacks. Where are we in terms of the understanding the cause of aging and when we can expect to see some breakthrough today?

Our guests is Martin bosh, Jason C S. O, A gordian bell technology, which is the first vivo therapeutic tic screening platform to improve drug development for a complete disease of aging before cofounded gordian, his poster and k ninety nine fellow at the book institute for research on aging. Hi Martin. welcome.

I am to be here.

So um maybe give a little bit about like what the school dian do.

Basically what gordian has advances since we started a couple of years ago is a way to put many drugs into one living animal test whether any of them do what you want, whether they prevent disease or reverse disease or reverse aging. And the reason this is important for biology of aging is that aging, and, you know, will get into this in the show.

But aging isn't like one thing, that one clock that's ticking down in all yourselves, and we know exactly what IT is. It's kind of a complex thing that happens within your organism, between the different parts of your organism. So the only way to really know whether something works in the context of aging is to be inside of a living animal. So that's why we admitted that technology.

So it's like a cocktail that injected into the animal, right?

Yeah but with the ability so you know some people will put you know three different drugs in to try and treat something, but they can't tell whether one or all of those are working together or individually. So what gordian has is that we can put many their peace in and individual cells inside of that animal. We can tell which therapy that sell got and whether IT was working. And so we can test hundreds of different therapies independently inside of the same animal, instead of getting just like a big, smoothly makes up of all the effects of the different drugs.

I know you have a background, you got a fellowship at the back institute. So maybe a lot of people they don't know about bug institutes, kind of like a prestige research institute. Aging, right?

Yeah, that's right. In the U. S. I would say this is the main research institute for aging. It's in located just northern empanel o and there is, I think, two hundred and fifty researchers, something like that with labs focused on various different kinds of aging, from new to generation to reproductive aging to specific mechanisms like sales. So I did my post before that. I did my psd at the main government research center for aging, which is the national aging part of the national institute .

of help in the U. S. The initial .

donor who paid for this big building, it's almost literally an ivory tower, is a big White building on top of the designed by I M. pay. There was an initial donor, the book family, and since then, they are supported both by grants from the government, like, you know, all the other research universities, as well as from various private donors.

Is there anything that kind of on the market already works still? Like how long has been this institute existence?

IT started, I believe, in nineteen and ninety nine, although then they had to build a building. So it's about two dede's ades old, but IT is a basic research institute. So the goal there is to understand aging and to generate knowledge around aging. However, there are several companies that have fun out of the book. Most well known probably is unity biotechnology.

Wow, unity is from there 哈。

Interest from the backend for male clinic, one of the scientific founders uh judy compete is uh at the book and I was actually the company was physically inside of the bar institute renting space there until they to south empties ago. Um and then more recently I think an apathy peos and B N B therapeutics and gear state alpha and I think that's IT in terms of being out.

So the other day I was talking to your code their friends is co IT is kind of weird because Normally when you think about biotech companies, they are mostly in bus in east coast and all the anti aging company is in the bay area like a lot of them. Is that because the bug institute?

I don't think that the only reason um the west coast tends to be more adventurous. Lets say right like there's a reason that the people who want to go to mars aren't launching from boston. It's like california, right? And the people who build A I and robots and all these things.

So boston is definitely a big by a take up, but IT maybe a little bit less sort of frontier. And I think the aging longevity definitely falls into that category of artic research. So that's my guess, although I do think that the buck probably played a role in creating a big hub here for longevity research. And I would say yes, sympathetic o is probably the in the U S. The top hub for uh, longevity research.

that's cool because this has been a domain has not been very little very hard for the past few years because has been in late AI. Like bitcoins, like crypto s those kind of domains are always like hot on the front of the newspaper, but not the entire aging. But yeah, I know the .

problem with the aging research is that you trying to make things live longer. So the experiments kind of take a long time. So it's not as fast as you know, doing stuff on a computer, but it's been growing.

I mean, certainly, i've been in the field a bit over ten years when I first joined. I was not like a Normal topic like people didn't really know what you are talking about at this point. There is a lot of interest. You mention altos earlier, obviously calo, a couple of other organizations that are starting up now with like very large budgets. So it's becoming more and more of A A mainstream thing .

that way is that is just because they feel bill in there. They just have their personal interest in this and in the poor money in like why is that or some tech that kind. I just have some breakthrough.

That's why we hear I think it's because stuff works. I mean, I don't mean stuff works as in like I have a drug that I can sell you and I extend your lifespan like we're not there yet. But I mean, animal models, we have a lot of different ways to make them live longer and prevent disease.

And that is relatively recent. The first before, let's say, in the sixty, seventy, eighty, ninety IT was kind of, you know, people were talking about, they have been talking about aging for thousands of years, but nobody knew anything. People didn't know. Like there is a big problems of the field paper that I read from like one thousand, nine hundred and seven years, something like that.

And one question was, are there any genetic changes that make you age slower like that, that wasn't known? And then in the late nineties, two different lives, tom Johnson and consequences in the okay, ian identified mutations in in this worm species that often used in lab experiments that made them live basically twice as long as Normal. And so, you know, there was a fundamental discovery for the aging field, but IT wasn't well known by any means, and there was no aging field.

So now that many people were paying attention. But before that, we didn't even know that we could, that you could extend lifetime right then. Since then has been kind of a steady trickle from like a little bit in the minds and then more in the two thousands where we found different ways where kind of modulate the rate of ageing in animal models, and that's just got more and more robust.

And now it's getting noticed that, oh, that's actually a thing you can do. And when you think about IT, that's like it's totally crazy if you could like double the lifespan or even add fifty percent of healthy lifespan to an organism like a human, we can do that yet. But the prevalent would be something like the elves of talk in, or something like that, right? Like just this, like totally different created is that have a total different perspective on life.

So when you think about the possibility the rate of aging can be change, that starts to be kind of a big deal. And I think that people like bases and various others are getting interested in IT because IT is such a big deal. The only reason that hasn't been a big deal before is is big bin like A A snake oil sort of area for a very long time, right?

I mean, we've had court on, quote, aging cures for thousands of years. They were, I think, the first time proof china supposed he was pedal quick silver by his anty eighteen people, right? I'm chu ong.

So it's been an area with where people have been promising things for a really, really long time and there has been zero delivery. And so I think the first things that in the last couple of decades, I started to have any real effect were overlooked for a bit. And now is that kind of they're getting attention.

It's like we are starting to final some like scientific proof that something might work. I know my husband has I think I was like three, four years ago when eliza just came out and then he started like had a subscribe of the elisia. And then I asked him, like, why did you stop? Like, why I did you feel anything after taking his like, no, I don't see you anything. You are not supposed to be anything after taking is how do you know that it's gona work? You can't .

exactly. And it's tough for you know these two problems for a company like elisia. One of them is that the benefits are gonna a be like decades from now, right? So humans aren't really mentally geared to that degree of delayed gratification.

Um and of course, there is some uncertainty like you don't know if that works and you won't know for a long time. And so it's hard to maintain enthusiasm to keep doing something. I mean, certainly to do a diet or something, eating appeal is easier. But and then the other problem for a company like elisia is that they are selling a product that is not going through fd approval. And so that means that it's not that regulated what they are allowed .

to sell and supplement and private on their description .

yeah exactly. And the problem for them with that is so releasing was trying to be a science based company and dunk trials and have evidence and so forth. But they're competing against people who don't necessarily, I want to do any of that.

So they are kind of spending some of their resources on billing scientific, but someone else with a different supplement if their Better sales per you know, they can just come and make things up and say things that aren't true. And then you know most people won't know what's true and what's not. So that's one reason why most of the companies, uh, in the longevity space are focused on making F, D. A approved or whatever comes they're approved, their peace for specific diseases because when you then go that you run into the talents that coron code aging isn't the thing that you can treat like you can't get a drug proof for just that IT has to be targeted that specific diseases.

So maybe we can to talk about a little bit like what are the mean approaches that people are developing their drugs, like we talk about all that they're doing reprogramme. We there's some other ways to accomplish the goal. So maybe you can give us little like a round down like what art approaches .

yeah to hopefully accomplish the goal. Um so in terms of the pute approaches, I would say the earlier I kind of follow on what happened in the research fields of the jing but you know like one decade later. So the earliest approaches which still exists have focused on biology around sensing of nutrient.

So there's especially two pathways, the incident sensing pathway, and which called the m tor pathway, with center protein we found in the animals that you, for those pathways, ge, you can make the animals live longer. And so they are drugs that are trying to target that kind of biology. Maybe the best known is called rap micon, which targets in tour.

In fact, in tour stands for a malian target of reproaching. So the protein was found to be the target of a drug. And the promising is an improved drought for uh, immo suppression during transplants.

But when you give IT to mice, to all mice, they live significantly longer. And so there are some companies that are trying to make sort of variance of that kind of biology to improve aging. There were some companies focused on telemeter telemeter.

This kind of dozens actually seem to be that important for aging and probably an insulting some people here. But certainly at one point they was considered just the big thing. Now IT seems more like they play some role, but it's not like an answer to everything.

Instead, one thing that has become a very interesting topic since the two thousand and tens is the idea of synthetic cells. And so these are our cells out in your body. You could think of them as like grump y retired cells. It's any cell in your body can turn into this state and IT kind of stops doing what is Normally doing in large a bit and then sits there and spits out various um signals including a information molecules and that seems to be bad for you in variety of ways, causing accelerated aging of different tissues.

And so a unity which we talked about before was um I think the first company to try to find module drugs that kills and decent cells specifically but leave Normal cells alone and they started I see I think there was in two thousand and twelve and since then there's, I don't know, two thousand and other companies that are trying to to kill ls and themselves. So that has been A A popular approach. And then much more recently is this partial reprogramming that you mentioned that our choice is focusing on.

This is yeah, we should probably have a whole thing on that. It's a interesting approach where you're trying to basically harness developmental biology and the biology that your body Normally does to turn cells into a not a Younger state but a more embryo like turn yourself kind of like into an egg again, almost. That's how you can visualize IT.

It's not strictly what's happening and there were a couple of papers in two thousand and sixteen and another one in two thousand and twenty one um that show that if you do this but you don't totally reverse yourself state, you just do IT partially IT seemed to reverse various features of aging. And so that's a new topic that still very fresh. Let's say that there are a lot of kinks to iron out. There's a lot of sort of how well does this really work. It's in the experimental stage.

We sure of these approaches are more like events where I kind of closer to the market. Can we say that?

yeah. So there have been clinical trials face two clinical trials on variants of replacing some cells. So unity had a clinical trial face two for australia riders, which failed a couple of years ago but still there now trying to push some eye drugs and their other companies doing listen cell. So I would guess that within the next, I don't know, five years it's gonna some version of uh republican and some version of the nesson still killing that's looking good. And in criminal trials, the reprogramme stuff is gonna more than ten years.

ten happening.

You can also say that we already have the first stuff on the market if you believe that you know republican is already an approved drug. There's another compound called mid formin, which is a drug uh given to type two diabetics .

for diabetic right yeah exactly.

So that's already you know lots of people are taking that um if you have diabetes and there are some data from animal models that aside from having a positive effect on diabetes IT also may have a general positive effect on aging. Now this hasn't been sort of proven in clinical trial and humans yet. There are people who are trying something called the tame trial T A M E uh whether y're trying to test made form and just for diabetes and theyve been trying to get funding for that trial for a while.

I heard that people in the entire aging space, and they're all taking that.

Is that true? Not at all, but some people are. Yes, there is a range of sort of like how adventurer again you are.

I think for all of these things, we have to remember that until you you've test like biology is tRicky if something works one way in one context and biology IT works differently in a different context and nothing is really, you know, it's not like one dimensional, good on one end and bad on the other end, and you just got to get more and more good stuff and like a very bad stuff IT. All depends on your specific genetics and what else is going on in your life. For instance, if you go on a diet, for most people, on average, that's probably good.

If you're overweight, that's definitely good. If you are under weight, then it's bad for you, right? Like exercise is definitely good for you in almost all circumstances.

But if you're out of food and your sort of walking through the desert, you shouldn't be doing push ups. So everything depends on, you know, the situation you're in. And the same is true for these drugs that they're tested in animals that are in a very controlled environment.

And we need to know what they do in in humans. And will they work in some people or in all people and so forth. So until that those things have been tested directly, we don't know for sure. And then the question is question that faces all these people in the eating field.

Um should you take my form in anyway which comes down to do you think that like the odds are in your favor, do you think that there a Better chance that IT does something good than that IT does something bad for you? And for my format, for instance, I think one reason that one is popular is that know tens or hundreds of thousands of abet s have been taking IT for a long time. So we're pretty sure there are not sort of serious negative effects. So the odds of IT being good don't have to be as high as you know, some other thing that might have orrible side effects.

Yeah I know this space. There's a lot of scientists, and they're doing a lot like a hacks on themselves like this. A article I was reading, the CEO of bio viva liz parish.

A SHE been injecting herself was to sly cockup virus and gene land for years. And SHE does look Young SHE just like anna doing that on herself tray herself like a patient zero. Is that like a Normal in this space?

And especially, I would say, the people who go to that degree of sort of biohacking. I don't know what your definition of sciences is, but if it's like I work at research lab at a university and I have A P S D, that tends to not be the people who go for the sort of treme mental stuff. There are some people. I think it's mostly um you know what gets covered in the news and in the media and so forth, right obviously the most extreme cases or what gets covered but ninety five percent of people at the buck institute or the action stood on aging or a place like that like aren't doing anything that not like everyone in the country, uh.

is doing so in terms of like the capital. So are there a lot of vcs are interesting to space right now or mostly just from like private family offices? Were lake just individual rich people?

There are interest from both of those. There are some things that are specifically focused on longevity things. So just sort of going off the top of my head, there is long gevalia und, which is here and this go coorg ming.

There's juba essence, which is based in the U. K. There's lunch ity vision fund. There's Apollo and germany. There is casco in germany, two, three more called some baran of leggett.

So there are a number of B, C funds that are specifically focused on aging biology. And then there are also plenty of sort of biotech funds that are interested in longevity. Unity was bc.

Behind that was arch and church, which is a very well known uh by tech V C. Here in the U. S. So they clearly had some interest there. Yeah and recent horror ves has invested in an activity companies, general catalyst, some of their sort of silicon valley biotech interested funds are also focused on that as well as obviously specific family offices.

Yeah cause I was curious because Normally the return cycle is like a ten years that probably not gonna cover the whole cycle of a drug development for especially at front space like anti aging. So when in terms of like their strategy, I would like why are they investing this place? Because definitely going take longer for their return.

yeah for sure. But you have to remember also that liquidity event for the VC typically comes much before there is an actual drug approval. So the majority of biotic companies that succeed IT or that don't fail that say their fade is to be bought by a former company somewhere around like face one, maybe face two clinical trials.

And so at that point to the bcs get their returns. Another path is that. The company goes public at which point, again, the pcs can cash out where regardless of what happens later in the market right now, you're seeing companies go public sometimes even before they started clinical trials, which is much earlier than I used to be. So I guess that that you know i'm not a busy, but I think that that's what's happening is that they don't need to see you know, most of the these aren't investing in the company hoping to go all the way to drag approval.

We did an episode about secured lic because there were some secured lic company when I P. O. For the past year.

Yeah, I compass for right.

So they just like there are not that far ahead in clinical trial, but they do win public. But in terms of like the space in anti aging, there are company like unity and some other company. But there the start market is not like looking really like kind of buying. So for example, unity when they went public in two thousand and eighteen, share Prices sixteen point seventy five and now is say two dollar and ninety six, kind of like a significant dropped. Like why is .

that for unity? That's very simple. And I think this is the general answer, is that unity had to face trial fail, like biotic companies rest a lot on their first program and maybe their second program.

And so unity had their flagship program and austerity authorities fail, face two clinical trials, and at that point, to their stock just totally tanked. So secondary ary markets, you know, they generally look at how are you doing in the clinic and every little piece of evidence for against is, you know it's gona affect your share prize for unity. They're gonna have a tough time coming back from that failure. They have one more program running. If that doesn't work well, my guess is the company is gonna use to exist.

Do you think that will affect the whole interest? Gent.

space doesn't seem true. You know I have that thought of like, you know, the first companies kind of have to succeed bright. It's Normal that biotic companies fail cynical trials like that's not what you want, of course, but most technical trials don't succeed through face three, most drugs don't work as for in the same way that most tech startups, you know don't become google or anything. So I think it's kind of understood it's not indicative of the aging field. It's Normal for biotech and general that many things end up not working.

What about other company now already went public like a frequency or like cuba, a jx? Those companies yeah koba.

I mean, also just like just the stuff work in the secondary market is just all about can you prove in a clinical trial that you think works? And can you get to revenue, which is usually in the form of our approval? There is considerable revenue that can be accrued from having partnerships with larger farmer companies.

But all that stuff, it's not I don't think it's like I made a view. Gravity companies in any sense is just like do they have stuff that's getting close to approval or that looks really promising in late stage finical trials and they don't. So then the sheer crisis low, if you go to sort of biotic companies, is that and look at their share prize over time, you gone to see these extreme jumps like you know three x or four x from day to day. That's when they announced ed, their clinical trial results, and that's when they went well, when IT doesn't go well, you see the same thing. But they don't .

have many chances really. If you have like one, two fails and they probably the company just like that, they seems to exist.

Most basic companies are centered around either one asset or one sort of drug candidate or maybe a class of drug candidates, but that are very similar to each other and therefore the quite correlated outcomes. And yeah when IT doesn't work, often the company becomes kind of like a omi company. Maybe they're still technically alive, but like nobody is very polish on them and there is a chance that they can miraculous ly pull off a come back.

But usually that doesn't happen nowadays. There is companies like gordian are different uh, in that there what's calls often called platform companies. So instead of being centered around a specific type of biology with one of more assets, the way unity is that was basically we're gona kill.

And then cells, we have these two molecules. We are focused on a platform that can discover a new therapy. So we feel the technology platform that isn't limited to just like a single asset but is hopefully much Better at identifying as is that work than other approaches.

And so that type of company, I think, will have a Better ability to whether the failure of any single drug and with the ride investors, there's a bit more patients. There are sort of the same S S, what you see in tech that okay it's okay that you're not succeeding yet because you're growing and growing and growing. And by the time you start cashing in, it's gonna a really big deal.

And so that type of company is not new per say. You could say that like the first batch company, genetic was a platform company because they just had a way to make new protein drugs. They didn't have a specific single asset. But then there was an interview phase where platforms wasn't really the focus and now they are starting to come back again. And in the last, I don't know, it's hard to put dates something.

but let's say, a decade. So you are selling to other people who are also developing and the aging drugs because your result.

you are the platform. No, not necessarily. So IT can be that you are selling your services to other companies. There are some companies that do that, let's say, uh, atam, why is there are sort of A I drug development or drug design company and so they their business model seems to be to make deals with lots and lots of a other companies and then takes small ownership of each of those drugs.

The dynamics of biotech are such that there are a sort of specific value inflection points where once you have just like a target for a disease for, like how to treat a disease that's not really worth much, then what you have shown in an animal that IT actually reverse this, the biology that you say IT will, then IT becomes worth like a lot more teeth or more. And in once you have any kind of positive data in a human, then you have another value infliction point. And so things aren't really like the golf standard.

Is, does a cure an animal of some model of your disease before that happens? It's not worth a lot. And so if you try to go really, really broad and just partners, everything with other people, your sort of cost of gods, your ability to generate a new thing has to be really, really low before you can make a lot of money there.

What ends up happening with most companies, even if they start out, uh, trying to do that thing, is that they venture decide that they want to have more ownership in the drugs that are coming out of their platform. And so they become like genetic or like moderna, they become a company that has a broader portfolio of things that they're trying, sometimes with interesting business structures where it's kind of spinning out asset as independent companies, sometimes not, but still going abroad by trying to own the drugs themselves. And that's also what god an does like we are a drug development company. Our business model is the same as genetic got.

You can do the same trajectory. And then once you you have a platform that kind also a business model and then you can also develop your own drugs .

yeah the fact for makes you more robust, right? That means that if one thing fails, not everything else, all the value in your company is tied up with that thing. The other reason you do a platform as well, at least for audio, the technology we've built is something that allows us to test dramatically more things in animal models of disease than other companies are able to. And that's because of what I told you before testing IT. What's called in vivo in a living creature is really when the first time that you start having high confidence um in whatever I said you have.

And so we've decided to take that point and really paralyze what how much we can do at that stage, not only because that makes us more robust, but also because we can map out every possible drug that you can imagine for a disease and then pick the one that has the best profile in vivo and move forward with that one into clinical trials because chemical trials are really expensive. So once you commit to one target or one asset and start moving IT into clinical trial, you're locked in for like hundreds of million dollars. And so you really want to know, you know, do I have the best one uh, beforehand.

for example, like google go like what are they doing? Because google has like really deep pocket. Do you think that's like a kind of like a good model to is just like rely on on a big company and basically, you are just good for a long time instead of going public like raising rounds and .

rounds of money? Yeah, I mean, I imagine their process comes the pro is that you don't have to get distracted with like what do investors want right now or once the market want right now now and you can maintain a long term vision. The cn is that you don't have in the same way that I started, does sort of the fear of death, sort of damage constantly have hovering over you .

and you're not working as hard maybe .

um it's calico is pretty secretive. So it's not clear everything they're doing uh IT is clear that they're doing both research that's very basic, you know just understanding how different aging processes work. Basically A D M M, not just similar to what happens at the park.

And they're doing some uh, dark development, mostly with drugs that they've a licensed in from other universities and things like that. Some of the things they're working on seem to be aging, but they also have a portfolio that's honestly just kind of cancer drugs. So of course, cancer is a disease of beeing, but is not really clear how that baLance is going to be moving forward.

And then they say they are doing various types of technology development. But overall, they haven't been doing a ton of publishing and they haven't started lot of sort of high profile trials. So it's hard to say what exactly calico is planning to do, presumably something very long term. They never that money. We talk well .

for drugs like a reproaching and uh, tics. So those are gonna be shorter term. We're gonna see they're gonna come onto the market and then reprogramming and other stuff for longer term. So for example, like what's the heart is like obstacle in terms of developing distrust? Is there still like class trials or is just some scientific like theory does not prove yet?

Yeah I mean, we don't know how aging works. We can say that anyway, we know a lot of things about how aging works, but it's not like we have a complete map of everything that's happening and therefore, we know exactly what to do. So when someone goes and develop drugs for synthetics, it's because there is a lot of evidence that seen the latics play some a role in the aging process and therefore, they have some tie to diseases of beijing.

But they are not playing like the entire role of what's driving aging. And so you are taking a bit to that for this disease killing the us. And cells are moving them in some way is going to have a big enough effect on the average patient, some of who might have developed the disease one way, some of who might have developed the disease a different way, that you are going na pick up a signal in millimeter trials.

And so that's true for all drug development, but it's at least that's true for aging. And for aging, there is a one big chAllenge, which is that most of the basic research that happen focuses on lifespan and making my live longer, things like that. But when you get to the clinical trial stage, you have to go after one specific disease.

And so there's a gap there where you take your aging drug and then you have to decide which disease do we go after. And so unity, different things did a lot of work on different LG diseases, eye diseases, uh of three is proudly others to figure out where do we think it's most likely that this drug on there's one disease is going to have an effect. And that gap well, IT is certainly making a lot harder for by tech companies to go after aging mechanisms because the whole premise of the aging field is that these mechanisms of aging are connected to many different diseases.

And so if you are measuring sort of the end of diseases and you were doing that over a long or period of time, then you should see an effect. That's what you were doing in the lap, right? We're feeding some drug and over time, you see less incidents of diseases.

But that's not how clinical trials are designed. For the most part, they are designed as you have this disease. And we're trying to reverse IT, and we're only looking at one single disease. And so that's A A barrier and a Better understanding exactly how do their biological mechanisms map to the manifestation of specific diseases would be very helpful for the field. The other big thing that's missing is biomarkers, which is ways of measuring what's happening biologging ally in a snapshot.

And so, for example, blood pressure or collect al or biomarkers of heart disease, because we shown over decades of work that if you have higher blood pressure, you have a higher risk of heart disease. What the field really needs is human biomarkers of aging that predict the incidence of multiple diseases. They can can tell you how biological old you are.

Because not only can you then measure those directly in clinical trials and hopefully get an insight into multiple diseases and what your risk of multiple diseases are, but also you can do IT a lot faster, right? Like for Jordan na, typical aging experiment, the way we do in the lab in a ternary trial, you'd have to start giving people a drug when they're forty and then follow them for forty years. We can do that right is impossible. So what we really need is some way to measure right now what's going to happen to you over the next forty years. And so that's a really interesting uh, topic in the field of sort of aging research.

Now we knows like we want to less than our teas, so we know that one of the is get short and then we like spend. So are we just barely scratching, like getting to know breading scratching the surface of the aging science, like how much we know about?

It's hard to say, right? Like what the I can tell you that what of the known unknown is we have, you know, depending on how you slice IT. But let's say, a dozen different types of biology that seems important for the aging process.

So we know that there are these various things within each of them. We certainly don't know everything. We probably know less than half of there is to know about this type of logy.

But maybe more importantly, we don't really know the relationships between these things. We know that short tailed eres can cause system cells. But in your actually body, how often does the nm results from short team? Where is something else?

Like what other relationships between these different biological mechanisms? Are there some that we should target? Because those are upstream of many other things that are happening.

This is a known unknown like we know that is that would be important to figure that out. And we haven't been able to yet. We just sort of slowly being away added. But then the unknown, unknown like what do we even know about aging? That's obviously very hard to say.

I guess my my guess is and this is definitely I guess is that with everything we know now, as I mentioned, we'll be able to develop drugs over the next I don't develop them over the next five to less than ten years, and then you have to run through trials that do something for aging processes and kind of show that they work over the next less than twenty years. And that's going to improve health in a broadway, but also in a limited way. You know, you're talking about, and let's say just guessing, twenty percent reduction of incidents of these different diseases.

Es, something on that scale, not more than that, which is gone to be huge, right? Like the economic impact and the personal so of objective impact of that is would be absolutely massive and easily. The biggest thing we can do, uh, for human health other than eradicating all infected is right. So certain ly, we should do that. When are we going to get like something that just totally blows your mind?

Live to one eighty? Yeah.

live to one eighty. Or take a really old and wrinkle person and they just really become Young. I don't really wanna guess, but probably not the next twenty years, probably. What's gonna. And first is that we're going to do that to some animals, maybe to like people's pets, like dogs and cats. There are some companies going after that kind of thing, which uh regardless of like the market for that as uh consumer sales and all that kind of stuff, if you just take someone's dog and makes IT, you know, make IT live to like twenty five people gonna like .

right yeah the people will buy IT all .

right yeah can I have some I think that kind of thing will probably be a catalyst for the field again and within the next twenty years that then go into that, explore a lot more focus because yeah, I mean, in the reason I spend time on biology of aging is but worth dedicating my life to that is that you look at the a graph of the incidents of most of the diseases that you are worried about getting.

You know, galaxy's s and cancer and heart attacks and IT just goes up like pretty much exponent entity with age. So there's something going on. There is some underlying biology that's making you're vulnerable to all these things when you get old.

And we've shown, you know in the worms and in the mice. And so for that, that underlying biology is something you can modulate. And so you know there's a lot of work to do to get to actually work reliably in humans, but doing that is the biggest labor we have on human health.

So um can I ask you what's your personal like routine to keep usefulness?

Sadly, it's like most of this stuff that's gonna you live longer, you already know it's gna make you live longer.

just exerting exercise.

don't smoke, eat less sugar, eat more vegetables, all those kinds of things right? So I did do um so there's something called intimate and fasting which now means all kinds of things the the aging that we're done IT typically means like eating every other day or if your mouse, that means eating every other day.

And so I did that during my c and part of my post stark for four years total just because I seem to in animals that seems to make them live longer. Now, more recently, we figured out that how much you want to be fasting, and these kinds of things depends on the genetics of the animals. And so what sort of the right could on, quote those of fasting and humans, we definitely don't know that.

Um that's part of the reason i'm not keeping IT up. The other part of the reason i'm not kept IT up is the same as the logic pills, right? Like you feel nothing nothing different and so you can maintain IT. And then when you get super busy, for instance, if you're running a start up, then you kind of just like it's easy to put IT aside because you feel nothing changing. Uh, when you do that.

I just have a co worker and he does uh, fasting every six months or so and then he does the maple syrup with kind pepper thing so he will be drinking that for a week and then I think for the last couple days of that week I can clearly ceda his brain is like super slow and just not working. Um yeah but um it's kind of like a trendy thing in the value is .

still right yeah for sure. And I mean, you know things come and go whether is like ice baths or right.

the trial chAmber, you can just yeah .

exactly and usually there's some kind of evidence that know in some kind of study either doing that to humans had maybe some effect on some markers that might be uh, index of health or you know you did IT to some mice and IT helped them and so there's often some kind of science behind IT. But like I said early in the episode, biog is really tRicky because something works in a certain way in one context.

Doesn't mean IT works in the same way in a different context. If my live longer when they eat every other day, does that mean humans live longer when they eat every other day? Or is IT because like mass, notably ism is faster. The humans are supposed to be like five days on, five days of else like we just don't know.

This is concluded him.

That's why we need by markers. I don't .

think about more question. Do you have anything .

you want to add? I guess I would just some things up as like we know a lot and we know this can work and we know there's a lot to figure out and we need to just do the important work, answer the important questions. I recently launched a grants program where we give sort of uh, academic grants to researchers to focus on.

The many things that we just don't know yet, instead of getting too caught up on, like whenever is the latest and greatest thing is like this is going to be the server bullet. This is going to answer everything like let's get biomarkers. Let's get ways of measuring whether things are working, like let's understand the context dependence of the value we have like there is a diamond mine bear. And I think we should focus on getting to that as fast as we can. I am not like complacent, like we just need to do more researchers want to take infinity like we should as fast as we can towards that, but not try to jump all the hurdles and just assume that something is definitely going to work before we know that that's true.

Got is more like a is still trying different material for the label, but we have more Better tools, Better computer, Better A I to help us to achieve faster.

I look at the right like neural that is not like a miro. It's like you have enough compute to do IT as my limited understanding of the field, right? But like there's a lot of infrastructure that makes all the amazing stuff happen.

cool. Thank you so much morning for joining us. Yeah, I learned a lot .

and he was fun. yeah.

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