419: Assessing Merck and Moderna's mRNA cancer vaccine

0:06Andrew Joseph: Welcome to The Read Out Loud, a weekly biotech podcast from STAT. I'm Allison DeAngelis.

0:11Adam Feuerstein: I'm Adam Feuerstein.

0:13Andrew Joseph: And I'm Elaine Chen. Today, we're going to Spain. Well, Elaine and I aren't. We're speaking to Adam and our colleague Drew Joseph, who were on the ground at the European Society for Medical Oncology meeting in Spain. This is one of the biggest cancer research meetings in the world. About 40 ,000 people were present, including Adam and Drew. And so we are going to get their inside assessment on the latest news in cancer research, including highly anticipated data from Merck and Moderna's cancer vaccine and a monumental new standard in lung cancer treatment.

0:50Adam Feuerstein: But first, a word from our sponsor.

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1:40Andrew Joseph: All right, Adam, Drew, can you hear us? Are you lounging on beaches somewhere? Do you have a I'm back in gray London.

1:49Adam Feuerstein: I am podcasting with a view of the Mediterranean right now. Well, okay.

1:55Andrew Joseph: Before you go back to your Mai Tais or whatever you're enjoying, tell us about ESMO. I want to start off with the juiciest, most eye-catching news of the week, which were these results from Moderna and Merck's cancer vaccine. What did the data show and how did doctors react to it?

2:12Adam Feuerstein: So this was probably the most highly anticipated data. I don't think it was the most impactful data at the conference, and we'll get into that in a little bit. But this is that personalized mRNA cancer vaccine called IntisMiran. We knew the study was positive because Merck and Moderna had press release that back at the end of August. And then we finally got to see the numbers. The top line was a 42 % reduction in the risk of disease progression. Now, antissomirant is given in combination with Merck's immunotherapy, Keytruda. So this is compared to Keytruda alone. And these are adjuvant melanoma patients.

2:52Adam Feuerstein: So these patients have previously had surgery to remove their melanoma.

2:56Damian Garde: And Allison, in terms of what it means, I think there's two avenues we can go down on that. One is what it means for melanoma care. And I think a lot of doctors who would normally treat this group of patients with Keytruda will start considering adding this as well. There are some open questions because some doctors are experimenting with adding immunotherapy before patients have their melanomas removed, and those data are promising as well. And so we don't really have a good comparison between these two approaches at this point. But then the other question is what it means for cancer vaccines, because this was obviously the first phase three demonstration of strong efficacy of a personalized cancer vaccine.

3:32Damian Garde: and doctors have been trying to make cancer vaccines for 100 years without any success approaching this. And so there's a big debate in terms of how broadly these can be used. Is it the type of thing that will only work in tumors that are generally amenable to immunotherapies or could have broader effects? And the two sides in that are mounting their arguments, but really you will only know with more trial data in different tumor types. But the fact of the matter is there's already enough momentum in this field that those studies are being launched or have been launched You know, we've seen some negative studies as well.

4:04Damian Garde: And so that just goes to show that they're not going to work everywhere. They might need certain combinations. So it is happening, but I guess the jury is still out exactly on the full impact.

4:14Andrew Joseph: How do the results of this cancer vaccine study affect cancer treatment more broadly?

4:20Damian Garde: Again, this study looked at combining Keytruda and this vaccine after patients have their melanomas removed versus just using Keytruda, which has been the standard of care for like 10 years now and really did improve outcomes in its own right. However, some doctors, and there's been some studies around this, have been looking at moving Keytruda, an example of an immunotherapy, giving patients that drug before they have their surgeries. and those studies are showing results that that can also add the benefits of just post-surgery Keytruda alone. So there are going to be some questions about which approach is better, this adding a drug post-surgery or maybe trying to treat patients with Keytruda earlier.

5:00Damian Garde: And where that really comes into effect is cost because basically in a few years we're going to have copycat versions of drugs like Keytruda that will be available hopefully at much lower prices, whereas it's quite expected that this vaccine will have a hefty price tag, to say the least. And so in terms of questions of cost and access, some people might look more toward treating patients with a Keytruda-like drug earlier, though, again, we don't really have comparison data at this point.

5:29Adam Feuerstein: And I had a chance to sit down with Moderna CEO, Stefan Boncel, to talk to him, and he reiterated that they are really going to invest aggressively in other types of cancer. They have studies underway. The next study we'll probably see is in kidney cancer, which may read out at the end of the year or early next year. And then the real big test of antismorin is in lung cancer. Lung cancer is really the biggest disease category when it comes to cancer. It's where Keytruda makes the bulk of its money and it dominates that market. So if antismorin can work in lung cancer, that would be gigantic.

6:10Andrew Joseph: So the way that this data was released was actually a little bit unconventional. It was published by this oncology site. They broke the embargo on the data. And when that happened, Moderna stock plunged. So, you know, it sounds like the data are positive. Why did the stock sell off?

6:29Adam Feuerstein: So, you know, we go to these conferences as members of the media. And so we get access to embargoed data. They give us an advanced look at the news that's going to be presented so, you know, we can get our stories together. And I luckily had pretty much written my Merc, Moderna, and Tissa Moran story on the plane over here and had finished it in advance. And then, you know, I was actually walking around on Thursday night and I looked at Twitter and I saw that, uh-oh, someone broke the embargo. and ultimately we published the story that was going to run on saturday we published it on thursday night and yeah there was a little drama there and adam can you explain what you made of the stock reaction um i was not surprised i think you know what we have seen in modernist stock price we've seen an ad about 60 billion dollars in market value since the end of august when they had press released that this study was successful that's a lot of market cap even if you're like the most bullish Intis Moran investor out there who thinks this therapy could work in lots of different kinds of cancer because, you know, they're going to split those sales with Merck.

7:42Adam Feuerstein: So I think this stock in Wall Street parlance, you know, it got ahead of itself. It was sort of overvalued. I was not surprised to see the stock fall, you know, when the data actually were coming out. I think it's kind of a sell on the news type of event. That was pretty much expected.

7:59Damian Garde: Adam, I think what you're saying is no matter how good the data would have been, because they were recognized as pretty good, like quite good, there was going to be a drop-off.

8:06Adam Feuerstein: Yeah, I mean, I think it was no indictment of the data. I think the data were, you know, basically as expected or maybe even a little bit better expected. I mean, Drew, you raised some of the outstanding questions and concerns that were going to be raised regardless of whatever the data looked like. So yeah, I think this is really kind of a market reaction and not really, you know, not indicative of the fact that these were bad data in any way.

8:29Andrew Joseph: So let's talk about some of the other data. I mean, at the top, you guys mentioned this Moderna Merck cancer vaccine may not have actually been the most impactful data set we got at the conference. What did you think was the most impactful data set?

8:43Damian Garde: Yeah, I think sometimes we're a bit more focused on data from new drugs. But I think one of the most impressive results came from a study of Amgen's Imdeltra plus AstraZeneca's MFINZ. And it was in extensive stage small cell lung cancer, which is a really hard to treat disease with not great outcomes. And basically the study showed that this combination, which is two different types of immunotherapy, outperformed MFINZ alone in improving survival. And it actually cut the risk of death by 58 % compared to Infinzi alone. And that translated into a survival benefit of 21 months versus 13 months. And this is the type of data that earns a rare standing ovation when presented in the room.

9:29Damian Garde: This was pretty impressive. And I think this will likely be the new standard of care pending approval and all that stuff. But it just shows that I think, you know, older drugs are finding new groups of patients and interesting combinations of different approaches of medicines can lead to pretty profound results. So I think that was definitely one of the highlights.

9:48Andrew Joseph: So another data set that seemed to impress doctors was one from Roche. Tell us about that.

9:55Damian Garde: Yeah, so this data set was interesting in itself, but it also reflects all the work that's ongoing targeting KRAS mutations, which I'm sure listeners will know from Revolution Medicine's success in pancreatic cancer. Revolution Medicine's now has an approved drug, Razonq? Is that how we're saying it?

10:13Adam Feuerstein: Razonq.

10:15Damian Garde: Okay, excuse me. Revolution's Medicine, Razonq, a little French on that, is approved now for pancreatic cancer and greatly extended survival on that, which was a huge milestone in a drug. And it targets what are known as KRAS mutations. And so there's a bunch of work going on targeting KRAS mutations. This Roche drug target something called G12C. And this was in a study in non-small cell lung cancer, and Roche compared its drug, DivaRasib, to two older KRAS inhibitors, one from Amgen and one from Bristol. And those earlier drugs have basically had so-so efficacy data, and as a result, they've never really taken off commercially.

10:53Damian Garde: But what the study showed is DivaRasib outperformed them. It cut the risk of death by 44 % and cut the risk of progression by 42%. And it was actually tolerated by patients better. So it was kind of like a win across the board. And so it was interesting to see because doctors are like, speaking of standard of care, this will become standard of care in this second line setting. However, doctors are also saying there are other KRAS inhibitors coming. So this drug will have a nice spot on the market, but it could very well soon have some competition.

11:23Adam Feuerstein: You know, we've seen just this consistent improvement in the way companies have been able to improve the chemistry of these drugs and unlock this target KRAS that was once thought to be undruggable. So now that leads us to this Roche drug, Divaracib, which takes this big step forward for G12C-driven cancers. I did spend a lot of time at this meeting looking at other forms of KRAS mutations. Probably the one that is getting the most attention is G12D. There are a lot of drugs that are targeting G12D. I saw some data from in the site that are again used in combination and that's for pancreatic cancer so in this case like a g12d inhibitor plus chemotherapy and the idea here is that you can get better response rates more durability and potentially less toxicity with these combinations so you know the field is just wide open the approval of rosin q for pancreatic cancer really set the race ablaze And now you've got all these companies developing all these different drugs in the KRAS family, all different kinds of combinations trying to improve outcomes.

12:32Andrew Joseph: This is a really interesting, exciting new avenue for treatment, these KRAS inhibitors. And anytime you get like this first approval of a medicine, there's always a lot of companies that are trying to follow on, see if they can develop their own medicines. is this a flash in the pan? Or are we seeing data that show that this could be a really exciting new avenue for treatment of cancer patients? What do you think?

12:58Damian Garde: I think that it is a very big deal, and that it is changing the treatment of certain cancers. And KRAS plays a bigger role in certain cancers versus others. So pancreatic and lung are two of the top targets. You know, it's interesting, there was some debate after the Roche presentation about, especially if those competitors come into lung, how doctors will choose which one they'll consider side effects as well as efficacy, of course. And there was a debate about, is it better to have a KRAS inhibitor that targets a specific mutation or KRAS generally? But the fact that they're having that conversation probably would have seemed like unimaginable even a few years ago, just give the speed of progress targeting.

13:37Damian Garde: And so I think that shows, yeah, this is quite impactful.

13:40Adam Feuerstein: Yeah, I talked to a couple of physicians who focus mostly in pancreatic cancer and, you know, just wanted to ask them, you know, what their job is like these days now that RaisonQ is approved. And, you know, they just have these smiles on their face all the time. Because, you know, before this, talking about, you know, standards of care, you know, it was basically chemotherapy. That's all that you could use to treat these patients with pancreatic cancer. Now they have this one targeted therapy and many more in clinical trials. So I think that they're feeling like, you know, after maybe being sort of left out of all the excitement at these cancer conferences, you know, they're now taking center stage and their patients are benefiting, which is the most important thing.

14:25Andrew Joseph: Drew, Adam, thank you so much for joining us. And please go back to enjoying your cocktails at the beach. Thanks.

14:32Adam Feuerstein: See ya. Sure thing.

14:37Andrew Joseph: Okay, so before we end this week's podcast, we do have some news to share. Sadly, our dear co-host, Allison DeAngelis, will be leaving us. This is her last episode. She is leaving stat, and she is joining Bloomberg News to cover biotech there.

14:57Adam Feuerstein: Wait, I have to get my hanky. Tears flowing.

15:01Andrew Joseph: Adam never cries. He never cries.

15:03Adam Feuerstein: It's usually when the person that I want to win the Great British Baking Show doesn't win, and then I cry.

15:09Andrew Joseph: Adam, you're getting to the heart of why I'm really leaving. It's that I just can't argue with you anymore about the Great British Baking Show.

15:15Adam Feuerstein: I get it. You're going to the great media borg in the sky, Bloomberg. You're going to get that ship implanted in your brain. Have they done that yet, Allison?

15:25Andrew Joseph: That's later. No, I really have had such a wonderful time with you and Elaine over all of these years.

15:34Adam Feuerstein: Allison, I thoroughly enjoyed podcasting with you over these many years. It's been a thrill, a joy, and I will miss it terribly. but maybe I don't know maybe we'll have you on as a guest occasionally maybe you know maybe you'll write a great story and we'll all be really mad over at stat because you know you scooped us on something and then we'll have to have you on the podcast to talk about it I think you mean to say

16:01Andrew Joseph: Adam when I write a great story that you're all going to be mad about over at stat Elaine are we worried about Allison being the competitor now what do you think I am slightly terrified but we'll make it through and Allison you can come on and make us sing anytime you want. Wait, Elaine's gonna sing? Well you can try. You can try.

16:26Adam Feuerstein: And Allison some of our colleagues also wanted to say goodbye to you so take a listen.

16:38Andrew Joseph: Allison this is Hyacinth. I'm sad that I won't be hearing you in the read out loud anymore. Who's going to talk to Adam about the Great British Baking Show. Seriously, congratulations, and I can't wait to read your work at Bloomberg. This is Daphne Zohar, founder and CEO of Seaport Therapeutics.

16:54Adam Feuerstein: Allison, we first met years ago at a networking event, and I'm not a fan of small talk, but you were curious and funny, and we skipped the boring stuff and went straight into a truly interesting conversation.

17:06Andrew Joseph: That same curiosity makes you a great journalist. You're not shy about asking the hard questions, and your stories have a balance that makes them really compelling.

17:15Adam Feuerstein: We loved having you as a guest on Biotech Hangout, and I'll miss hearing you on the Read Out Loud.

17:22Andrew Joseph: Hey, Allison. This is Jason Mast, STAT's general assignment reporter. You were one of the first people to welcome me to STAT, and the first person to introduce me to the restaurant, Din Tai Fung. And for both of those, I am deeply, deeply grateful. It's been an honor to break news with you over the years. You've taught me so much with your tenacious reporting, your relentless sourcing. I wish you the best of luck at Bloomberg and can't wait to see what you're going to do. Hi, this is Teresa Gaffney. I'm a reporter at STAT and a former producer of The Read Out Loud. Allison has been such a kind and generous coworker.

18:04Andrew Joseph: We're really going to miss her. She has helped me out countless times on reporting, on different stories. She's been generous as a friend. She helped me move. She scoured around Somerville and Cambridge to get me boxes so I didn't have to buy any when I was packing up my apartment. She's always down to lend a helping hand. She always brings a smile. And while I'm really sad for the Staten Newsroom, Bloomberg is so lucky to have her. Allison, we'll miss you. Stay in touch.

18:41Andrew Joseph: Oh, you guys. You're trying to get me emotional. Thank you guys so much. I love you guys. We love you too, Allison. We love you too, and we're going to miss you so much. Adam's going to make me lose it. This is not something I want to hear. This ugly crying from Adam.

19:08Adam Feuerstein: That does it for another episode of The Read Out Loud.

19:11Andrew Joseph: Our podcast is produced by Rachel Gottbaum. Our senior producer is Alyssa Ambrose. Our executive producer is Rick Burke. And our theme music is by Brian Joel.

19:20Adam Feuerstein: We'd love to hear from you. Tell us what you like about this week's episode, what you didn't like. And tell us how much you're going to miss Allison DeAngelis. You can do all that by sending us an email at readoutloud at statnews.com.

19:34Andrew Joseph: And if you like what we do, leave a review or rating on Apple Podcasts or wherever you get your podcasts. We'll see you next week.

19:41Adam Feuerstein: We're not going to see you next week.