[Music] Welcome to this week's episode of The Read Out Loud, a weekly biotech podcast from staff. I'm Allison D'Angeloos. I'm Adam Forrestine. And I'm Elaine Chun. It's Thursday, June 4th, and on this week's episode we'll speak with a mother of two boys who is diagnosed three years ago with metastatic pancreatic cancer. She joins us to discuss her diagnosis and treatment, which is included revolution medicine's directs and rassib in a clinical trial. But first, a recap of the week's news and a word from our sponsor. [Music] I'm Mika Kakathuda-Durink, SPP of Oncology at Gilead Sciences. At Gilead & Kite, our work in oncology starts with a simple question. How do we make progress truly meaningful for patients? Since 2020, our therapy has been used to treat more than 75,000 people worldwide with metastatic, triple negative, and HR positive, her two negative breast cancer. We'd bring that same patient first mindset to other areas of high-end met need, including CAR-T cell therapy for people with difficult to treat blood cancers. Today, over 34,000 patients around the world have been treated with CAR-T cell therapies from our portfolio. Across oncology, this perspective guides how we design clinical trials and pursue innovation so patients can access potential advances throughout their treatment journey. Learn more at gilead.com So, Adam, how was Chicago? Chicago was great. Elaine, you live there. You know, it's a nice time of the year to be in Chicago, the weather was fantastic. No rain, it was in the 70s. I didn't get to do a lot of sightseeing or fun stuff because obviously we were working, but it's always a nice time to be there. I have to say, the way that Chicago utilizes the lake front, I think is really special. There's just miles and miles of walking past and trails along the lake, which I don't really like that. People make fun of the concrete beach, but at least we have the lake front. I would honestly rather lie on a beach than lie on a concrete slab than on sand. I'm very anti-sand personally. I'm also anti-sand because I just burn, but that's another story. Should we get into the biotech news, folks? Sure. Well, it has been a blood bath for biotech stocks this week. As of yesterday's close, the XBI has fallen 5%. I know there's a lot of people out there that are saying, damn, just as the XBI was really starting to regain traction. Elaine, tell us about one of the companies that experienced a major drop. Yeah. Let's talk about ABBAVACS, which I should caveat is not actually in the XBI, but it was a major sell-off broadly in the biotech industry. ABBAVACS specifically reported this week that it's experimental treatment for ulcerative colitis, showed significant efficacy in a closely watched maintenance trial, potentially the best long-term efficacy we've seen in ulcerative colitis so far. But investors were focused on a few cases of cancer among treated patients. Specifically, in this trial, there was one case each of prostate cancer, breast cancer, and colonic dysplasia in the group taking the highest dose. But investigators determined these cases were unrelated to the treatment. There were also four cases of non-melanoma skin cancer in the highest dose group. ABBAVACS said two of those cases were deemed to be not likely or unlikely to be related to the drug, and among the remaining two cases, one patient had a history of skin cancer. Majority of cases, at least according to ABBAVACS, not related to the drug itself. Yet we saw this huge fall in their stock. Do you guys think the market reaction was overblown here? Because the efficacy was really great. It was a crazy reaction. When this happened, it was Monday night, Monday evening, East Coast time, and I was actually in the newsroom or the press room at Asco. So it wasn't paying super attention to it. I guess the initial reaction that I saw, like Elaine, you said, was really positive. This maintenance effect that the drug, I guess we'll call OB, because that's what I have. It's the nickname OB. It was kind of the best in class. Then I just happened to click over to see how the stock was reacting, because I figured it would be up a lot. I saw the stock was down like 15-20 percent and they're like, "Huh, what's happening?" And that's when I started hearing about this malignancy, this cancer risk that had come up in the study. It was crazy. This is a very, you mentioned Allison, that this impact that this had on the broader market. This was a very widely held stock. It's not in the XBI, but it's a very widely held stock because of the potential for this drug OB in all sorts of colitis and other I and I conditions. I'm prone. I'm prone. I'm prone. Exactly. That coupled with a couple of other stock companies that had some setbacks and failures at the same time, I think kind of contributed to the sharp sell-off overall. As to whether it's recovering, I mean, the stock does seem to be recovering. If you looked at yesterday and Wednesday and today, the stock does seem to be coming back. I think, Elaine, to your point, that there's now, maybe with a little bit more time and analysis and thought that these cancer diagnoses that were picked up in the study were kind of random. This was not something mechanistically that would be attributable to the drug. There's probably still going to be kind of an overhang and I don't know how long that persists and it's something that will have to watch as this drug, this longer follow-up. It was quite the reaction. Something pretty unusual to see. Adam, how much do you peg this to kind of larger things that were happening on Wall Street earlier this week? Or even the fact that biotechs can fall into a bit of peril in larger markets when there's nuance or things that need to be dissected in clinical data or considered, as we're seeing here with these cases of cancer and the question of whether or not that's related to treatment. Yeah, I think it's all that. Alison, one of the issues here, the concerns is that this this drug works in an entirely new way. It's a different mechanism to tackle ulcerative colitis. And so therefore, there's always going to be some uncertainty about the benefit, but also the safety because we have seen cases when you do test a drug that has never been tried before in a new way of targeting a disease. Biology, things happen. Biology can throw surprises at you. And so we don't know, ultimately, that's kind of the long-term question. Is this something related to that mechanism or not? And again, there seems to be indications that it's not, but we'll have to wait and see. And then, yeah, just the broader market, you always have this idea of biotech, how it exists within the broader market. You're competing with tech companies and AI and all these other different kind of investments. And it's difficult. Particularly if you look at the broader market, how investors are just in love with anything AI related these days. And so biotech gets a little bit of the cold shoulder. Yeah, but it's kind of related to what Alison was saying. I feel like biotech is just not an industry that's kind of suitable to the way that kind of trading and investing typically across where there's like a binary like this is going to be. It is very nuanced. And yeah. No, I agree with that. Yeah. I mean, again, it's the kind of the one industry where literally you can wake up and news comes out and either your stock is up 5x or it could be down like 99%. That's there's so much volatility. And it's one of the reasons why people like investing in biotech. But it's also another reason why a lot of people just avoid biotech. Okay, so let's get into some of the data that was presented at ASCO last weekend. We got new data from Ivanismab, the bi-specific antibody developed by the Chinese company Akizou and its American partner Summit Therapeutics. They reported that Ivanismab reduced the risk of death in patients with squamous non-small cell lung cancer by 34% compared to a standard treatment. And this was in a trial conducted entirely in China by Akizou. So the result was good. It exceeded a lot of oncologist expectations, but it also added the debate around
whether trials conducted in China lead to better results than what we would have expected with studies conducted anywhere else. - I think that's a really good last point to hit Elaine because the big question that has been circling around a Kizu for what the last two years is to what extent the clinical data collected in China will translate over to American and European patients. And so I don't think that the presentation at ASCO really answered that question. - Yeah, and I was there. It was a very long like three plus hour plenary session. I was in the room. And these exact questions were raised by the discussing Julie Braemer from Hopkins who analyzed and discussed the Ivo, Ness and Meb, clinical trial. And that's one of her big takeaways was that we're not, based on these results in the way the study was analyzed, patient characteristics, that's still an open question. Will this benefit seen in the study translate into a broader global population? That study is being done. Summit is running a basically identical clinical trial. It's called Harmony 3 and those data will be out. Well, at least the overall survival data will be out a little bit later this year. We did learn earlier, a month or so ago that, that they did run an interim analysis on a progression-free survival endpoint that did not at least meet that sort of high hurdle at the interim, which has raised some question marks about the translatability of all this from the Chinese study. But that is definitely an open question as we left As we left Asco. - We also got some interesting follow up to a conversation that we had on this very podcast in April. Listeners might recall that two months ago, Eli Lilly announced it was buying a colonial therapeutics in a $3 billion deal. We had venture capitalist Brian Roberts on the podcast to talk about the company's really rocky road up to that point. And on Sunday, Colonia presented an update that gave an idea of why Lilly opened its wallet. They presented data that among 18 patients with advanced multiple myeloma, a one-time infusion of Colonia's In vivo CAR-T therapy resulted in a complete response rate of 28%. And an overall response rate of 100%. All 18 patients achieved minimal residual disease negativity, meaning that there were no detectable cancer cells on an ultra-sensitive blood test. So another good win for Colonia. - Yeah, you know, when we had Brian Roberts on the podcast, Alison, you know, we joking with him, we said, well, we, you know, we clearly, there's more data that we haven't seen. And Lilly has seen those data, which is why they're spending billions of dollars to buy Colonia. And so yes, these are the data or among the data that obviously Lilly had gotten a chance to see before any of us. I was in the room, I was in a sci-sad in on this presentation as well. I was busy in Asuka this year. But Lilly's chief dealmaker, Jake Van Narden, was also he was sitting the row, actually sitting the row ahead of me. And we did chat, he goes, you know, this is before the presentation. He said, yeah, these data like science fiction come to life. That's what he said. So, you know, they were clearly excited about it. And the data looked good. You know, this is, as we had mentioned, you know, this is a new approach to CAR-T therapy for multiple myeloma. These, this is an in vivo CAR-T. So these are, they're, you know, editing cells inside the body versus outside. It's an unproven approach, but something that would be very beneficial potentially to patients. So, you know, still early days, but you can see why Lilly was excited. - Okay, Adam, but tell us about the most boisterous room at Asuka this year. - Yeah, so it will be no surprise to anybody that the headliner at Asuka this year was Revolution Medicine's drug, their Ras inhibitor, Diraccin RASIV for advanced metastatic pancreatic cancer. Yeah, it was a pretty traumatic, like I said, this was in the plenary session. It was the same session where the Ivanesimab data were presented. And, you know, the, the presenter was up there, Brian Wulpin from Dana Farber, Kent's Institute was presenting the Phase 3 study, you know, we just near doubling of overall survival, you know, really striking results. He's going through the presentation and just as he starts to talk about the survival benefit, the room breaks up, breaks open into applause and cheers. And when I say room, think of like half of an ice hockey arena, so we're talking like 18,000 people in one - Oh wow. - Shy normus. Exhibition hall auditorium, okay? We're not, this is not a little room with a few hundred people. This is literally like 18,000 people listening to this presentation, this talk. And right in the middle, standing ovation. I've been going to Asco for many, many years, have seen other standing ovation during talks, including plenary presentations, but never interrupting a talk like mid, mid talk. That was a first. And it was really quite, it was quite, and I think it was an emotional moment for a lot of people just given how challenging and how lethal pancreatic cancer is and how profound these results are for patients. All right Adam, thank you for the Asco dispatch. Elaine, next week, we're going to get an ADA dispatch from you, you're going to be covering that conference. Tell us what you're looking forward to. Yeah, so the American Diabetes Association conference is this coming weekend. It's diabetes, but really it's, in recent years, become more of an obesity conference. We'll have some key readouts that people are watching. So we'll have data on the GLP-1 drug developed by Metsera, which Pfizer acquired. This is supposed to be ideally a once-monthly GLP-1 drug, which Pfizer thinks will make it more attractive than the weekly injectables we have on the market. So we'll see data there. We'll see more detailed data on the least triple G drug, red or true tide. We'll also get a GLP-1 glucagon dual agonist developed by Boeing or Ingolheim. This is a more unique combination of GLP-1 and glucagon. It's supposed to be especially targeted towards people with fatty liver disease or mesh. And then a GLP-1 small molecule pill developed by AstraZeneca. So we'll have a lot of data this weekend. Stay tuned next week for more obesity news. We're gonna spend the rest of the podcast. Oh, actually, Leana, I should say that there will be a part before this where we kind of go over all the data and talk about it. So we're not gonna waste your time with that. Okay, we go. We're gonna spend the rest of the podcast talking more about pancreatic cancer and directs and rassib. Importantly from the patient perspective. Leana Stokes lives with her husband and two sons just north of New York City, where she is the manager of a gymnastic facility. In 2023, Leana was diagnosed with metastatic pancreatic cancer. Leana joins us to discuss her diagnosis and treatment, which is included directs and rassib in a clinical trial. Leana, thank you so much for taking the time to be with us today. Absolutely, thank you for having me. Leana, so as we just mentioned, you were diagnosed in 2023. Tell us about the circumstances behind your diagnosis and behind your decision to seek medical help at that time. Absolutely. So when I was diagnosed, I was at a point in my life where I was taking care of my son who was one year into active treatment for ALL, leukemia. So at that time, I wasn't taking care of myself. I was putting my own health on the back burner and drinking coffee on an empty stomach and eating late in the day. And I had what to me was a stomach ache and turned out to be acid reflux just from poor habits when my mind was elsewhere. And my primary care doctor, he wanted to just check the boxes and send me for an ultrasound, which he says is not common when it's an acid reflux issue that kind of resolved on its own and with not on its own, but with my attention to diet and such. Luckily, he did send me for that ultrasound and that led to a CT scan, which led to my stage 4 diagnosis in 2023. Exactly a year after my son's diagnosis. So to say that it rocked our world is the biggest understatement. And I think the circumstances behind your diagnosis, Liana, you know, so to run your scur as how one of the big challenges with pancreatic cancer, which is, you know, early tumors grow and they're really aren't kind of the symptoms that alert a patient or a physician to the fact that someone has cancer here. Of course, and my
labs, my standard lab, CBC, CMPs all came back normal. And at the time, I had one mass in my pancreas and hundreds in my liver. And my liver function on my CMP was normal. So even something like that, my white count was not elevated. You know, there's just so many other indicators that with so many other different diagnoses that you might see that with pancreatic cancer, it just doesn't come to be. And I remember he called me back in for labs after I had my ultrasound before having a CT scan. And he, I say, I'll say fifth. And he told me he was doing more extensive of a liver panel because he said there was confusion in the liver. You know, he kind of knew what he was looking at, but didn't want to scare me just yet. And that's when he did my tumor markers. And obviously that is something my CA 1999 and my CA, those are indicators of the pancreatic cancer, rather than a regular standard blood test. So it is. It's scary because so much of pancreatic cancer goes undiagnosed until it's late stage. And this, as you were saying, is happening during a really difficult time for your family, you're actively, you know, helping your son through his own leukemia treatment process. How did that experience and everything that was happening in your life impact your decision making when it came to your treatment plan? And what kind of options you were going to pursue? Right. I, by the time I was at MSK, because I did my biopsy elsewhere, got a confirmed diagnosis elsewhere. So by the time I got to MSK and in front of Dr. O'Reilly, who is a world renowned doctor in pancreas cancer, by the time I got in front of her, it wasn't emotional. It was, tell me what I have to do. I've seen my son go through it sadly at the age of five, he was diagnosed. Strong as you could imagine chemo treatments in the morning, doing obstacle courses in the backyard in the afternoon. He was unbelievable throughout his treatment. So in my case, it wasn't, it wasn't, will I be treated, it was, I'm going to be treated by the best. I'm going to find out what I'm going to do and I'm going to give it everything I have and throw everything at it and try my hardest to kind of also supplement what Dr. O'Reilly is saying with some lifestyle changes to make sure that I'm giving it my best chance. So when you went to see Dr. O'Reilly, your tumors were analyzed and you learned that you had the K-RAS G12V mutation. Correct. Did that mean anything to you at the time? What did Dr. O'Reilly tell you about that? At the time it meant nothing until she told me about it. She explained to me exactly what it was and how important it was to have that and kept talking about this drug that was in trial that we have this drug and it's groundbreaking. It was very early in trial at the time of my diagnosis, but she kind of like kept it in her back pocket. She was saying, this is for the future, this is for the future. So I did two lines of chemo before it was my turn for the Dr. X and RASIB. So for me, it was an option in the future and no matter where I was in my treatment plan and still to this day, I just look for options. That's always been my goal is because I don't want to like so many other oncology patients. You never want to run out of options. So to hear such a promising option that was set in the future was really something special. We kept talking about it and kept talking about it and I kept plugging along in my chemo treatments until it was time. You said you include I guess two different rounds of chemotherapy and they were helping you for a while. The cancer came back and I guess it was at that point where Dirac and RASIB became an option for you as Dr. O'Reilly had said to you, tell us a little bit about that and what you told you about it and how you came to take the drug. Sure. So I did a total of 34 rounds of chemo and it was a combination of a Fulferinox Fulferic combo as well as a gem site of being a brachsane combo and it was always in the future, the trial. When it came time, I was put into a trial without randomization because I've had two lines of chemo. So there was the type of trial that with one line of chemo there was randomization to either a systemic form of treatment or the trial drug. So when I went in, once it was presented to me as this is your option, that's where Dr. O'Reilly and the team kind of took a back step and they didn't really say much and looking back now, I know now it's more because she wanted me to make my own decision and that was a decision that I had to make with my husband and my family to decide to, in my mind, how I put it was abandoned chemo. So when you abandoned chemo, it's kind of like that safety net is no longer there. It's a safety net that I had for at the time a year and a half and not, it was a great safety net but chemo is not fantastic but you know, you take that away and you put your trust into something that's being tried out. So they kind of took a step back the whole team and they let me make that decision on my own. Once I made that decision, it was like the doors opened and they vocalized just how fantastic of a decision I made and how promising this is and they really dove into that arena of this is groundbreaking, this is going to be huge kind of thing. Once I've, once I made my decision, which I completely respect, I think that this is a very personal decision for every individual. It's a very big life changing moment for many people and it was something that I had to do on my own without the influence of the doctors and I was happy that I made that decision at the time and we started pretty quickly. I had to go through some testing, some biopsies to get on trial but it was a great decision. Yeah, how did your body, your cancer, respond to directs and rassib? So it was a very quick response at first and the activity in my liver shrunk very quickly. After a while, it plateaued and I was fortunate enough to be able to be on the trial drug for 10 months and the thing that they're, I think, investigating along with side effects, of course, which is a huge thing is your bodybuilding resistance. That's what I got to in the end of the 10 months but at the beginning it was a very quick response that my activity shrunk very drastically in my liver and the biggest change, obviously you want shrinkage, obviously you want your disease to respond to the drug but it gave me my life back and that's the biggest part. For 10 months I was able to work five days a week, be mom, be a wife, you know, go to the beach with my kids, ride bikes, have a catch, all the normal things that I would do as a mom and a wife and an employee and a boss and all these things that are normal life for me, that's what it gave me back. So I know so much of it is about data and statistics and numbers and shrinkage and that's great but I think that there's a quality of life that goes along with it that is equally as important. What were your experience with side effects? You know there's been discussion about the rash for you personally what were the side effects that you experienced. It started out mostly as a face rash on my chest on my back. I worked very closely with the dermatology team at MSK to try to get that under control which it did. The hardest part because the face, I didn't get, I got to a point where it was painful and it was and it was pretty bad but we got under control which was great and that was, that was perfect. The hardest part I had were, I had open wounds on my cuticles and that was difficult because at any given time I had anywhere from two to seven fingers out of commission. So it was hard. I got to a point where I did ask for a break at one point during treatment because I couldn't tie my shoes, I couldn't wash my hands, I couldn't put my kids socks on. So it was, that was challenging. It was the hands, I think, was the hardest part. The rash on the face, once it was under control, I was able to manage it but it was the hands, the functionality wise, I couldn't tie it, it was very challenging. As we mentioned in the early part of the podcast, direction.
and Rasa was the headliner at the just concluded ASCO cancer conference. And you know, the study results showing a near doubling of survival for pancreatic cancer patients. And that data, those results were met with this just incredible standing ovation from the oncologist and researchers who were in attendance. Leana, did you hear about that? And what's your reaction to that? Yes, I did. I saw some of the videos from ASCO and it was, I got chills. It is, it's a very important ground breaking moment in this disease and it brings such joy to me that I was a part of something that I, that my data was taken and I was a part to hopefully have this approved and this can be used for so many other patients going forward. It feels special to me and I hope to be able to use the drug myself in the future once it's been approved because I did gain a little bit of a resistance to it and I had to come off. However, Dr. O'Reilly is very, very open to the possibility of getting back on it and hopefully seeing a disease response again after some time, taking some time off. So I am just very excited for the future of this drug and the breakthroughs that have come from, from all this research. Yeah, one of the messages that was coming out of ASCO this last weekend from oncologists who treat pancreatic cancer patients, including Dr. O'Reilly was that Ras inhibitors like Diracson Rasib represent a really fundamental change in how this type of cancer is treated and they're really optimistic for patients. How are you feeling about all of this? How are the other patients that you talk to feeling about this? I am feeling very hopeful about it. I think that it's something that is, is going to be a great tool in the future and I know that there's talk about it being utilized as a first line of treatment which is even better to be able to utilize this type of a drug prior to needing chemo. You know, obviously stage matters if there's metastases where it has metastasized to. There's so many other factors but the fact that this can be used in such a wide range of patients because the Ras mutation is so common in pancreas cancer that I'm very hopeful for the future of treatment for pancreas cancer and I'm hopeful for myself because I'm still in it. It's not others, it's me too. So I'm hoping that this just continues to see good results and gets that fast-tracked approval by the FDA so that it could be used more widely for myself and other patients. One of the criticisms you hear or read is that the improvement in survival that's seen with the Ras and Ras and Ras and maybe it's not enough or it's not meaningful or impactful and obviously you've lived through this and I was wondering how you respond to that. When you see the results and you think about what is the drug that's done for you, what's your perspective on that? I think any improvement to survival time is an improvement especially when it's personal. It's easy for somebody to say that when they see it on paper, when they see it at a presentation, you don't see the personal side to that. You don't see the personal story behind those numbers. When you see the six months versus the 13 months that they're talking about, that's not somebody's personal life. That's a number on a screen so that's a big difference for somebody that's going through it. That's why I think that those numbers are very important for the patients and I have been very fortunate. I am two and a half years into treatment. I don't take survivor totals lightly. That was also one of the decisions that made me jump into the trial was that when it was first being presented to me, I was looking at the previous data sets and I had surpassed the months they were talking about while on chemo. It made me say, "Why not? If I can extend my life and I have two beautiful young children and a husband and a wonderful family and a wonderful support system and the longer I can be with them, the better off I am." The difference of months may not be huge to some people but to every individual patient that that data set is talking about, those months matter. Yeah, Leana, how are you doing today and how is your family doing? What has this whole experience done for you all? Being able to be on directs and rasive changed our normal back to normal. That was something that I do not take for granted the 10 months I was on it. Like I said, I was able to get my normal back and be myself and I found myself again and that was fantastic. Unfortunately, I did gain the resistance. I am back on chemotherapy. We have a lot in the pipeline, Dr. O'Reilly and myself, between some radiation and possible hysterectomy. I do have a lot of things in the works. As far as my family, we are fortunate to have been able to have those 10 months of normal C. This is not a setback. I do not think it is the last time I will take it. I am hopeful that I will be able to be on it again and experience that normal C as long as I can get there and it gets FDA approved and I can plug along on my current plan that Dr. O'Reilly has for me. Myself and my family, we are very hopeful that it will be a part of my future. We are very grateful that hopefully that can come to be soon. Well, Piana, thank you so much for coming on and sharing your story and we are hoping the best for you. Yeah, Liana, thank you so much and best to you and your family. Thank you so much. I really appreciate it. That does it for another episode of The Readout Loud. Thank you to Hyacinth and Banado for producing this week's episode. Our senior producer is Alyssa Ambrose. Our executive producer is Rick Burke and our theme music is by Brian Joel. And we love to hear from you. 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