Hello everyone and welcome to CrownCast, the podcast from Crown Bioscience exploring emerging trends and perspectives in oncology, drug discovery, and drug development. I'm your host for today's episode, Michelle Dawn Mooney, and today we are discussing the important role that biomarkers play in advancing precision medicine and improving drug development. Joining us is Julie Mayer, Vice President of Crown Bioscience's Global Biomarker Platform. Julie brings extensive experience in molecular diagnostics, translational medicine, and biomarker strategy. Before joining Crown Bioscience, she held leadership roles at NeoGenomics Laboratories and previously led laboratory operations and clinical assay development across several organizations focused on advancing precision medicine. She earned her undergraduate degree in biology from the University of California and later completed both a Master's degree and PhD at the Keck School of Medicine at the University of Southern California. Julie, thank you so much for joining us today. To get us started, can you tell us a little bit about yourself, your background, and ultimately what led you to your current role at Crown Bioscience? I landed, here at Crown because we're doing some exciting things in the area of research and translational medicine. Happy to be a part of Crown and leading the global biomarker platform to, you know, advance medicines to patients quicker. So, thanks for, chatting today. And thank you for sharing that. So I want to begin with the basics. When people hear the term biomarker, what exactly does that mean, and how are biomarkers used throughout drug development and clinical programs? Sure, yeah. Biomarkers are pretty general term, right? So they can be everything from normal biomarker functions and processes to pathogenic processes, or even responses to therapeutic indications. So, biomarker as a term is very broad and can be used in a variety of ways. I can think of, you know, there's like target identification, you know, you can use them to identify pathways of disease, things like that, or mechanism of action, patient selection, as we move towards translational and clinical. Gosh, people use them for safety, efficacy, dose selection. I think biomarker in general is a very broad term. And, you know, lots of platforms and things to be used that way. But in general, yeah, we do a lot of testing across this and the organization. And, you know, a lot of drug development companies will be using a very targeted biomarker strategy to move forward. So when a company begins developing its biomarker strategy, what advice would you give? What are some of the most important considerations organizations should be thinking about early on in the process? Gosh, the first thing that comes to mind is start early, right? Think about biomarkers ahead of time. Of course, because I lead the biomarker platform, I'm thinking that at the forefront. But, you know, if you start to think about that early in your strategy, you can develop it in your pipeline during target selection. You know, this allows a very specific approach to your strategy. Develop it comprehensively. Look at it throughout your strategy. You know, address key clinical questions biomarkers can be used for. There's, again, many biomarker types. So there's predictive and pharmacodynamic and kinetic and pharmacogenomic and so on and so forth. Think about the broad phases that you're in and how things can be used throughout the process. Of course, you want to ensure quality and reproducibility across your strategy. And, you know, my favorite, plan for companion diagnostics in the future. You know, how are we going to bring this test to market? How are we going to implement this in the clinic today? What are we going to do? And it sounds like establishing that strategy early can have a significant impact on later stages of development from selecting the right patient populations to helping address potential challenges before clinical trials begin. So I want to talk about biomarkers in clinical practice. What are some of the most common types of biomarkers being used today? Yeah, exactly. Diagnostic, prognostic, predictive, PK, response biomarkers, susceptibility and risk biomarkers, monitoring safety, those kind of things. I think on the area of diagnostic biomarkers, there's plenty of examples of those that are in use today in the clinic. Things like ER/PR, HER2 for breast cancer or PSA for prostate cancer. These are routinely used, you know. Additionally, that's put forth a lot of biomarkers in production use for solid tumors, things like EGFR for lung cancer, or KRAS, ALK and ROS, all of the latest markers that are actively used in clinical trials today. And I think the list goes on and on. First, solid tumors, hematological tumors as well, right? For CML, for instance, BCR-BL has been a key biomarker that has had dramatic impact in the clinic today and on outcomes. But yeah, prognostic things like BRAF mutations, for instance, for melanoma, and how those are predicting response, or EGFR can be considered predictive. I think the list goes on and on for all these variety of classes. And companies like Crown are testing for that and doing research on this every single day. Crown Bioscience has extensive experience supporting both preclinical and clinical biomarker programs. Can you explain the differences between biomarker testing conducted for research purposes versus testing that supports clinical trials and patient care? What additional requirements come into play there? Yeah, I think, clinical biomarker testing is, you know, an essential component of personalized medicine and, particularly guiding cancer treatments. So, the closer you move into the clinic, the more validated, these markers are for their intended use. I think where things differ are, you know, the level of quality assurance and compliance. There's a lot of regulations and as you move into the clinical space, in addition to the ISO certifications, there's CAP CLIA and of course, FDA requirements here in the US, and other global regulatory implications and agencies across the world that you must comply with to bring things to market globally. But we are doing our best to participate in external quality compliance testing to try to ensure harmonization across our sites, and that we're doing things in a very harmonized way. Again, I mentioned FDA, I think we're moving towards this in the states for even LDTs. So I think there will be more over the next few years on that as it develops with the FDA. But our labs are CAP accredited and moving towards CLIA certification, in the US. But yeah, I think we were trying to stay on top of it. We're trying to maintain our, you know, continuous education across our laboratory staff and make sure that we're on top of all the latest education and topics. As biomarker testing moves into regulated clinical environments, validation and quality standards become increasingly important, as you know, to ensure consistent and reliable results. Have you seen examples where proper biomarker validation, or maybe the lack of it, has significantly influenced the success of a clinical program? You know, you want to make sure that you're validating, to the intended use of your assay. Otherwise, the drug will not proceed forward to make it to the clinic, or it won't be effective. So, I think it's important that we aim to standardize the validation requirements. That's what these large agencies do. They ensure to harmonize and that folks are meeting the same requirements, right? Not only to bring this to market, but also to some companies and diagnostic labs to get paid, right? So it's important to improve overall health outcomes for patients. I always love hearing about the real world stories. So can you share a few examples where biomarkers have made a meaningful difference in improving patient outcomes? Sure, yeah. I mean, mentioned earlier, I think BCR-ABL, I think, is probably the most, one of the most notable success stories, right, for CML patients. So I think pretreatment overall survival rates for imatinib, right, as the drug, were somewhere in the thirty percent to fifty percent range for five year survival, and now they're above ninety percent. So I think it's quite a success rate when you identify a target, a biomarker target that you can treat a patient with. I think that's key here, prescribing patients the right medicine at the right time for patients. And that's important. I think we can mention a few others that have led since then, right? HER2 for breast cancer has been quite impactful with trastuzumab and a variety of other drugs since then. And even lung cancer now, right? We're constantly innovating and bringing new drugs to market to create a longer lifespan and give more hope to patients. Progression free and overall survival is what we're going for. But yeah, there's a lot of biomarkers in this space that we're bringing. You've spent many years working in this field. How have you seen biomarker technologies evolve from early single gene assays to today's multi omics approaches, spatial biology, digital pathology, and other advanced technologies? I think when we started, they were very single gene assays, right? PCR assays or IHC assays, and they have progressed to more multi omics based approaches where you have many targets. And, you know, we're realizing that pathways are interrelated and things are connected. And so, you might have a biomarker that says you should do one treatment, but then you have another biomarker that's positive that indicates you may have resistance, or you may not be a good candidate for other drugs. So, I think overall, we are progressing, we're becoming more omics related, we're integrating, we're getting more diverse in our testing strategies. And I think the future is being shaped by these technological advancements that we have. And it's exciting to see that these are all data driven, these are, you know, really moving towards the area of precision medicine. So, you know, there's a lot of key trends in the space. You touched on the multi omics. I love the aspects of liquid biopsy and being able to be less invasive with testing. I've spent a long time, in this space, and, I think we can detect things a lot sooner and have better outcomes as a result of certain, testing modalities like that. With these increasingly sophisticated technologies comes an enormous amount of data. How important has bioinformatics become in helping researchers analyze and then interpret all of that information? Absolutely. Yeah, I think as data becomes more complex, then so does the analysis and the software algorithms that are developed as a result of it. Again, more exciting outcomes because the more data you have going in, then the more data there is coming out, right? So, you can identify things faster rather than one gene at a time, or, you know, one protein at a time, you're doing a lot of things at once. So, I think this is going to touch in in the future on AI and AI generated algorithms. But again, I think moving towards non invasive and large data sets, large omic platforms. You mentioned proteomics. I think proteomics today is yesterday's NGS. So I think we are moving into this space because that's the active area of growth. Looking ahead, what trends or innovations do you believe will have the greatest impact on the future of biomarkers over the next several years? I mean, I really do think it's going to continue in the areas of AI, integrating these large proteomic, genomic, just multi omic kind of data sets and cohorts to predict therapeutic responses and outcomes. But, you know, yeah, the integration and complexity will be an initial hurdle, but I think software developers and bioinformaticians will quickly advance this space. I think things are going to move towards more liquid biopsy type, noninvasive methods to diagnose or identify these faster. I think you're seeing that trend. And just the non traditional aspect of growth. I mean, the traditional methodologies will always be there. They'll get more complex and more multiplexed or more innovative kind of technologies that come out to kind of speed things up, I think we're moving in a more multi omics integrated kind of fashion. I think that trend will continue, but being able to do more with the samples you have will be interesting to see how that unfolds. How important is it for organizations conducting global clinical programs to work with partners that have an international footprint and consistent capabilities across multiple regions? Yeah, I think it makes it easier to easier in one regard to help harmonize across the globe and to actually bring novel platforms to market across areas that may not have access to some of these technologies or access to some of these results that they could be driven. On the clinical aspect, this allows for global clinical trials to happen and in a very harmonized kind of way, but meet the local regulatory requirements. Having labs globally. I think a lot of companies are moving towards this trend as well. Hard to believe we're almost out of time. Julie, before we wrap up, are there any final thoughts or advice you'd like to share with researchers and organizations looking to strengthen their biomarker strategies or maybe learn more about this rapidly evolving field? I think just continue to aim to standardize testing across the globe, right? Bring these novel biomarkers to and medicines to patients faster. I think that's the goal here. We want to improve overall patient care and outcomes. And we're on a mission to try to do that, right? To improve overall health and make an impact to the patients that are diagnosed with cancer. So appreciate the time everybody, and thanks for listening to the end if you made it this far. Look forward to having more conversations in the future on biomarkers. Thank you so much, Julie, for sharing your expertise and your insights today. Appreciate your time. It's a fascinating conversation, and we do appreciate you taking the time to join us today. So thank you for being here. And I want to thank all of you for listening today. We hope you found today's discussion informative and valuable. If you enjoyed this episode, be sure to subscribe on your favorite podcast platform, or you can visit www.crownbio.com to learn more and explore additional CrownCast episodes covering the latest topics in oncology and drug development. Thanks again for listening. I've been your host, Michelle Dawn Mooney, and we'll see you next time on CrownCast.
