What Sets Immunity Project Apart | Naveen Jain & Reid Rubsamen

So Reid, do you want to maybe tell a little bit more about sort of why we're different? Give a little bit more detail? Sure.

What's your name there?

Akshay.

Akshay? So Akshay, you want to be in the pharmaceutical business. You want to make a lot of money, help a lot of people. What's the most business profitable kind of drug you could pitch to a venture capitalist? So you want the venture capitalists to go, I want in, man. I want all of this. What's going to turn those guys on the most? What are they looking for?

Story.

Well, okay, so they wanna make a lot of money, obviously. They wanna put an investment in. So what they want is they want a chronic disease that lasts for your whole lifetime for which there is expensive, effective therapy. They want you taking that pill every day. They want you spending thousands of dollars a month. They want you completely dependent on it. They want it patented. That's what they want. So what are some diseases? So HIV is such a disease in North America. So you can live a normal life with HIV by taking these antiviral medications. They're very expensive. And so vaccines, like, the worst business model, right? 'Cause you give one shot to somebody and they don't get sick. So where's the excitement there? Like, you know, move on with your idea. So it's not easy to get vaccines funded whether you give 'em away or not because they don't sound good in the classical business model of pharmaceuticals. And that's starting to change. Because if you're a government, especially with a single-payer health system, you're gonna hang on to that person for their whole life. So you don't want them to get HPV and get cervical cancer. You don't want them to get HIV or hepatitis C, for which there currently is no vaccine. And so the government of Australia paid for every single adolescent boy and girl to have HPV vaccine because they know if there's cancer later, Australia, which has a single-payer health system, will have to pay for it. So, So we are already different because we're in the vaccine space. We're already— and then we're doubly different because we are trying to use a computer model in conjunction with sort of this basic immunochemistry platform. And we're also using a vaccine platform that doesn't involve recombinant human protein and does not involve any dead or live virus. It's a very simple mechanism that uses only the targets identified by the computer model to attack. So you're not using any dead or live virus? cells that are infected with HIV. And the third thing, of course, is we're trying to do this for free, meaning without getting any royalty stream back to us. So those are very different kind of things. And the first thing we did when we started this project to understand the landscape of potential support out there was to do a crowdfunding campaign. And like people in the— What's a crowdfunding campaign? medical business like me, we don't know a lot about communicating on the internet. And Naveen and Y Combinator, we went to Y Combinator and they helped us do this. It was fascinating for us to see all the support there was for an idea like this out there.

So I think one of the biggest challenges we've faced with Immunity Project is it's It sounds too good to be true. So actually, this is advice that PG gave us. He said, the number one problem you guys are going to have is that it just sounds too good to be true. How is it that you guys have figured out a potential solution for something that many other pharmaceutical companies, many other researchers all over the world have been working on literally for decades, have spent tens of billions of dollars trying to solve, Why are you 2 dudes and your team the folks to figure this out? And so my answer to that question is that I think that the biggest innovations that are going to happen in our world going forward are going to be blends of disparate skill sets, are gonna involve blends of disparate skill sets. So in this case, you have a novel blend of computer science and biology, and I think that is one reason. So if you look at the traditional drug development market, most people who are biologists or researchers sitting in a lab, they're not very comfortable necessarily even with computers. They're very comfortable with lab equipment and doing things in a lab, in sort of a lab environment. They don't necessarily understand, wow, you could use a computer to iterate, to very rapidly sort of test and try to figure out, using an algorithm of some kind, what possible weak points on any given virus might be. So I think that's one reason why I think we're unique versus many other groups that are out there. Second reason is we're attempting to mimic something that already works. So 1 out of 300 people who are living with HIV have a natural immunity to the virus.

Wow.

Now most people don't know that. So 1 out of 300 people living with HIV have a natural immunity to the virus. So these are people that if they come into contact with the HIV virus, it doesn't necessarily progress to AIDS. They might still have a viral load. There are different shades of gray here in terms of how, quote unquote, immune you are to the HIV virus. But these people exist, and we call them HIV controllers. So the question is, And by the way, we're not the only group attempting to ask this question. What makes these so-called controllers different from everybody else, from anyone in this room versus a controller? And by the way, some of you might be controllers. You just don't know it. So what we've sort of figured out, and again, as Reid mentioned, in partnership with Microsoft Research, is we think that they have better targeting capabilities in their immune system. So their immune systems are able to identify these biological markers on the surface of the HIV virus that happen to be the virus's Achilles heel. And when you attack the virus at these locations, it forces the virus to mutate into a dormant state that it can't easily mutate away from, and it renders it essentially inert. And that's how we think HIV controllers work. Now, there are other hypotheses out there, but that's our hypothesis. And so what we were able to do is, working with Microsoft Research, We were able to essentially design software to attempt to reverse engineer these so-called HIV controllers and figure out what are these targets. That was the question we were trying to answer. What are the specific targets on the HIV virus that these so-called HIV controllers are preferentially targeting and therefore rendering the virus inoperable or inert? That's essentially the work then we carried forward with our drug delivery system. And I'll talk about the crowdfunding thing in a bit. But why don't you give a little bit more detail about the drug delivery system that you and our team invented?

Sure. So basically, as Devine said, there's this interesting factoid that 1 in 300 people are controllers. And better than that, there was a guy at Harvard— is a guy at Harvard who actually collected blood samples from several hundred of these people and put them in a freezer. So the researchers at Microsoft were able to go back to that database of blood and using a technique— I won't go into a lot of detail, but it's possible to do a chemical experiment to figure out from the blood itself what part of the virus the immune system of an individual is preferentially targeting. And they did a very elaborate experiment to decode that targeting sequence in each individual test tube. And by using a machine learning algorithm, they were able to go through and get a very specific target list of known targets in HIV favored by the controllers. So they published that list in an article in a journal called Virology last year. At about the same time, we published our article on our platform that we designed working with one of the Microsoft researchers. And our platform uses a biodegradable microsphere the same size as an antigen-presenting cell and some molecules called adjuvants that fire up the immune system and get it all excited about being attacked. So the idea is a Trojan horse. We put a particle inside a subject. And they go, wow, I'm getting a horrible infection. They think that because these signals that we're sending with the adjuvants say, wow, infection present. So the immune system attacks our vaccine and then dissects it, and what it's going to find are these preferred targets in HIV, and it will educate killer T cells in the body to go after those targets if that HIV virus were ever to show up. So it is a— the plan is to get a durable response here where Years later, if you get an HIV infection, your killer T cells will attack and kill any cell that's infected with that virus. So that's the sort of elegant design objective and it really is driven by this natural historical analysis of these marvelous people who have an intrinsically very, very, really randomly but intrinsically happen to attack the virus at these preferred points. It's the firmware of their immune system that does that and we think we can copy that firmware in anybody by the use of this vaccine. It's almost a reprogramming of your immune system to go after these same targets.

So most people don't think about this, but everyone in this room is under attack 24 hours a day, right? So you actually have more bacterial, viral, other sorts of things' DNA in your body than your actual human DNA. And your immune system is what keeps you safe, right? So your immune system is essentially what's protecting you from any of these possible infections from carrying forward. But as everyone I'm sure in this room believes, I know there are people out there who don't believe this, but these things evolve. They change. They're not static. So bacteria are always mutating and they're always trying to figure out how to gain an edge. And your immune system is evolving right alongside. So your immune system is learning, if you will, on an ongoing basis. And you've got marvelous machinery In all of your bodies that execute on this process literally 24/7, every single day of your life. So as Reid mentioned, what we're essentially doing is we're harnessing this natural ability that you all have to learn about anything that your body comes into contact with. Short of something like HIV that is A, attacking your immune system, right? So you have a finite number of bullets, if you will, in your immune system gun. And B, is mutating very rapidly. That's the problem with HIV. That's why HIV is so challenging of a virus to solve. So our thought process is, OK, if we know what the targets are on the HIV virus that are preferred by HIV controllers, is there a way to essentially teach anyone else's immune system about those targets so we can essentially turn them into a controller as well? And so that's what our team has developed, is using, as Reed called them, these biodegradable microspheres. So think really small bubbles. About 11 microns in diameter, right? And we have a patented process where we can essentially take these targets and put them in and around these spheres, right? And combine these spheres with chemicals, call them adjuvants, these are chemicals that cause an immune response. So the idea is that it really is a Trojan horse in the very direct, tangible way of thinking about a Trojan horse, except it's happening within your body in real time. And our goal is to teach your immune system. Yes?

What's the size of HIV? So you said your Achilles heel immunity is 11 microns. What's the size of HIV?

You mean the virus itself?

Much, much smaller. So can we show the video of the phagocytosis? Do you have it on there? Let's see if I can figure that out.

It's the same thing with Trojan horse, right? Just being much smaller.

Yeah, well, of course the Trojan horse is very big and the Romans got inside the horse, right? Where we have the sphere itself is like the horse and the targets are like the soldiers inside. So the dendritic cell says, wow, I'm seeing this thing that I should be concerned about. I'll take it inside my cell. And you can see this is a time-lapse photograph. This shows these are the antigen-presenting cells called dendrocytes here. These big black things are our spheres containing the vaccine. They're taken up by the cell. The cell then disassembles That's here and says, "Oh, I see these targets in there. I'm biologically programmed by nature to make those targets of interest, and I'm going to program killer T cells to kill anything that shows those targets at a later date." And what targets we put in there are precisely those targets that HIV controllers prefer. They're very tiny, eleven amino acid long targets called class one epitopes. Yes, sir. Are you a big killer? Pardon me, sir.

Are you a big killer? No.

No, no. So the next step— actually, I met with the FDA yesterday with the director of the Center for Biologics. And the next step is for us to meet with the FDA, explain all this to them, and then file what's called an investigational new drug application, which is permission to test in humans in the US. And we actually are going to file that in the US. We probably may actually test it in sub-Saharan Africa, where the incidence of HIV is much higher. But we will do that with a US application. Yeah.

So in terms of— does that give you guys a pretty good understanding of how this vaccine works and why we're different?

OK.