Moderna个性化癌症疫苗三期临床机制与数据

It's the first time there is a cancer vaccine working. The field has been doing that for 20 plus years, more than a thousand clinical trials that have all failed.

What was different this time? What is it about mRNA technology that enables the immune system to learn in a way that other approaches were unable?

We all have cancer cells all the time in our body. Our immune system is very well trained. Basically notice those cancer cells very early and get rid of them. But if your cancer grows, then the question is how can you retach immune system? We're going to basically take a biopsy of your tumor. We're going to read all the letters of its DNA. And then we're going to do the same things with a healthy cell of your body.

And we're going to literally compare letter by letter, nucleotide by nucleotide. And then we're going to use an algorithm to identify which one of those mutations are the most relevant. And so when this is injected in your body, it teaches the immune system the signature of your cancer cell that it missed.

What gets regulated here? Because every dose is different. So obviously every dose doesn't get approved.

Busy feet.

Hi. Um, welcome to the A16Z podcast. Uh, I'm Horge Kai, a general partner on the A6Z bion health team. I am thrilled today to welcome back Madna CEO Stfan Bonsel. Um, for folks that have been longtime listeners may recall, uh, Stfan joined us on the A6Z podcast back in December of 2020. um when we were talking about all of the work Madna did to uh bring us the the mRNA COVID vaccine and at the time um if you can go back and listen to that episode you'll hear um how quickly um Madna was able to react to the existence of the virus to analyze it uh to essentially print a vaccine um that would protect people against an uh against the the the co 19 uh vaccine and hence put us in a much better position uh with respect to the to the co pandemic.

We titled that episode the the machine that made the vaccine and the reason why we're talking again today in August 2026 uh is because Madna has uh put out news uh on a really big advancement on what they can do with mRNA technology when it comes to cancer. And so I want to hand it over to you uh Stefan uh again a very big welcome. Thank you for coming back. But maybe the place to start is let's uh let's lead with the news.

Um you uh Madna and Merc uh announced uh earlier this month in August that uh you had uh uh conducted a phase three clinical trial in melanoma and have gotten uh very encouraging results. So why don't I hand it over to you and tell us uh what have you announced? What have you seen in this phase three trial and then I do want to dig in into what Madna is doing in cancer.

Wonderful. So Roy, thank you so much for having us back. We're very happy to be to be with you. So indeed uh last week now uh we shared the news with our colleagues at Merc that after working 10 years on a individualized uh treatment against cancer using MR&A technology that the phase 3 was positive it's a it's a first of many it's a first time that there is an agent in melanoma that is better than kudra alone so it's a big deal for patient of course with melanoma it's the first time there is cancer the vaccine working.

Uh the field as you know has been doing that for 20 plus years. I think more than a thousand clinical trials that have all failed. Um and um if you look at the phase two data because what we announced last week is that we met the primary endpoint of the study which was recurrence free survival i.e. people having the cancer back or dying

that we met and then to our own surprise because this was the first interim analysis. This is not the end of a study. It's a first interal of a study and what was a surprise even to us is we met the secondary endpoint which was distant metastasis free survival which is of course takes more time to mature because it means that you have distance metastasis from your primary tumor and we also made that uh endpoint which was great again unexpected from our side but again means it is really good.

Um we will share the data very soon at a big medical oncology conference which is as you know what the field does. But just to give you a sense maybe to orient kind of directionally we showed at ASCO the big you know oncology conference in the spring of 2026 a few months ago that our phase 2 study which was also randomized against ketra alone. So the same type of study showed that around 50% of people had recurrence free survival versus people only getting kudra and this is 5 years after treatment and as you know incology five years is considered by doctor like a cure and so it's a big big deal and if you look at the data from organ that phase two you had around 80% of people that were disease free five years after their treatment and their surgery of melanoma And so we're very excited about what it means for the field.

Uh we are working very hard already with regulators to file so that the drug can be available to patient as soon as possible and we hope in 2027 and we're going to try to make it as fast as we can. Uh the factory is ready in Massachusetts but we have figured out how to make and scale a product for every human being at the at the time.

Well, there's I mean there's so much to to unpack here. So I um this is an extraordinary uh advance uh for the the treatment of in this case melanoma and hopefully over time cancers more broadly. Uh so let's unpack some of this if we could Stefan. Uh the first one um uh uh talk to us uh for folks that are less familiar with cancer treatments. Uh why is Kuda what is Kruda and why is Kruda alone not sufficient? Why was Madna necess or the the the this particular mRNA cancer vaccine necessary in conjunction with Kruda?

Sure. So if you look at Kudra which is kind of one of the leading imunotherapy that people might have heard of is basically if I oversimplify for nonbiologist it's basically a molecule that basically open the gates for letting the dogs out that are going to go and attack your cancer from your immune system if you want. Um the the thing about checkpoints is when they work they're fantastic because those people 5 years after treatment are in the cured in the sense they have no remaining disease.

Uh but only 60% of people are disease free after five years if you look at the phase three published data of kudra. So again for those 60% of people it's amazing but it means that there's 40% of people where you go through the treatment you're fighting for cancer and the treatment doesn't really work for you and also what is difficult is those treatments are wonderful but they a lot of time come with very serious side effects very different from chemotherapy or radiotherapy the side effect of imunotherapy are mostly immune disease

so you see people if you look at the label or the clinical studies people that get checkpoints Whether it's Kudra or any other type of checkpoints from other companies, they end up having type 1 diabetes, lupus, chron disease, these type of things. Of course, it's better to have those disease than of course being dead from your cancer, which is why those have become standard of care. But think about those 40% of people who don't respond to checkpoint.

They get an autoimmune disease most of the time and they don't get the benefit of a medicine. And so what we try to do with Merc and is really a technology that emerged from Mona Labs back in 2015 2016 when we did a partnership with Merc as we're looking for one of the best company in imotherapy to partner and to have a complement approach the idea that we have at the time using our infectious disease learning from our infectious disease vaccine.

We learn a lot about the immune system and how mRNA interact with the immune system. We thought we could develop a mechanism of action that was totally orthogonal. So very different from imunotherapy because you will be able to start from a sequence of your tumo