NASDAQ:EXAI Exscientia Q1 2023 Earnings Report Earnings HistoryForecast Exscientia EPS ResultsActual EPS-$0.38Consensus EPS N/ABeat/MissN/AOne Year Ago EPSN/AExscientia Revenue ResultsActual Revenue$7.10 millionExpected RevenueN/ABeat/MissN/AYoY Revenue GrowthN/AExscientia Announcement DetailsQuarterQ1 2023Date5/24/2023TimeN/AConference Call DateWednesday, May 24, 2023Conference Call Time8:30AM ETConference Call ResourcesConference Call AudioConference Call TranscriptSlide DeckPress Release (8-K)Earnings HistoryCompany ProfileSlide DeckFull Screen Slide DeckPowered by Exscientia Q1 2023 Earnings Call TranscriptProvided by QuartrMay 24, 2023 ShareLink copied to clipboard.There are 13 speakers on the call. Operator00:00:00Hello, everyone. My name is Chris, and I'll be your conference operator today. At this time, I'd like to welcome everyone to Exensio's Business Update Call for the Q1 2023. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. Operator00:00:28At this time, I would like to introduce Sarah Sherman, Vice President of Investor Relations. Sarah, you may begin. Speaker 100:00:36Thank you, operator. A press release and 6 ks were issued this morning with our Q1 2023 financial results and business update. These documents can be found on our website at www.investors. Exensia.ai, along with the presentation for today's webcast. Before we begin, I'd like to remind you that we may make forward looking statements on our call. Speaker 100:01:00These may include statements about our projected growth, revenue, business models, preclinical and clinical results and business performance. Actual results may differ materially from those indicated by these statements. Unless required by law, Exensia does not undertake any obligation to update these statements regarding the future or to confirm these statements in relation to actual results. On today's call, I'm joined by Andrew Hopkins, Chief Executive Officer Dave Hallett, Chief Scientific Officer and Ben Taylor, CFO and Chief Strategy Officer Gary Perito, Chief Technology Officer and Mike Kremz, Chief Quantitative Medicine Officer, will also be available for the Q and A session. And with that, I will now turn the call over to Andrew. Speaker 200:01:47Thank you, Sarah. Today, we're going to talk about a differentiated approach to personalized medicine, how we use complex, primary patient tissue samples as preclinical models. Combining this with our in house multiormous capabilities, we can go from target identification all the way through to the clinic. 2023 is off to an exciting start as we continue to advance our pipeline and strengthen our business. We've made significant progress across our internal and Partner programs include an advancing 2 molecules into the clinic, EXS-four thousand three hundred and eighteen and EXS-two thousand one hundred and fifty six. Speaker 200:02:24An additional molecule, DSP-two thousand three hundred and forty two was advanced by Sumitomo Pharma, which was a result of an early collaboration with Exensio but is now complete. This marks our 6 novel molecule created for Exensia's generative AI platform to enter the clinical stage. We've expanded our precision oncology pipeline by initiating IND enabling programs for 74,00539, an LSD1 inhibitor and EXS-seventy three thousand five hundred and sixty five, a MULT1 protease inhibitor. More recently, we presented multiple posters of the AACR Annual Meeting, highlighting research that continues to validate our end to end approach and demonstrates the potential of a platform to rapidly advance high quality drug candidates towards the clinic. Our team's commitment to strong execution has enabled us to rapidly move programs from discovery through to the clinic. Speaker 200:03:19We have achieved a number of milestones already this year. In March, we announced 2 new wholly owned precision design molecules, an LSC1 inhibitor, 539, and a multi-one inhibitor, 565. Both programs continue to progress through IND enabling studies. We expect to provide an update on clinical development plans in the second half of this year. We remain on track to meet our target of 4 candidates with meaningful economics for Exensia in clinical development by 2024. Speaker 200:03:48In February, Bristol Myers Squibb initiated the 1st in human study of EXS-four thousand three hundred and eighteen, our potential 1st in class selective PKC Theta inhibitor, 4318, was designed by Exensia and is currently in Phase 1 clinical trials in the United States. Earlier this month, the first patient was dosed in IGNITE, our Phase onetwo trial evaluating EXS-two thousand one hundred and fifty six or 546, Our A2A receptor antagonist. This was the 1st AI designed immuno oncology drug in the clinic And we remain on track to dose the 1st patient in a Phase onetwo study of GTA EXS-six seventeen, our precision designed CDK7 inhibitor co owned with GTI Paragon in the coming weeks. We also remain well capitalized with $553,000,000 In cash at the end of the quarter, this provides us with several years runway to advance our near term programs without the need to raise external capital. On today's call, we'd like to provide more detail on our approach of combining precision design with personalized medicine. Speaker 200:04:58Before handing over to Dave Hallett, our CSO, I want to highlight a recent scientific presence at this year's AACR meeting. We presented data further validating our ability to efficiently design high quality drug candidates and to identify and predict the right patient populations that may benefit the most from treatment. Firstly, for 546, we presented research on our adenosine burden score or ABS. It showed that 506 reverses the effect of adenosine analogs ex vivo in patient tissue samples and other complex models. The ABS has been validated in our ongoing IGNITE Phase III clinical study of 546 and will be discussed further today. Speaker 200:05:42Ignite was designed based on extensive simulations to enable the most effective continuous reassessment method settings to predict and accurately evaluate The anti tumor effects of 546 in combination with checkpoint inhibition. The team also presented preclinical data On EXS-seventy four thousand five hundred and thirty nine, our precision designed LST1 inhibitor. We designed 539 to optimally target LST1 in future Oncology and hematological patient populations. These preclinical data demonstrate that 5C9 has the potential to Lastly, we highlighted the benefits of using data generated with Exensio's Precision Medicine platform in combination with its Proprietary methodology for multi omics and multimobile mapping. By better understanding disease mechanisms, These tools combined can be leveraged to improve patient outcomes by uncovering clinically relevant drug targets already at the discovery stage. Speaker 200:06:50We will go into more depth in this topic shortly. In summary, we have 5 programs of economics that are either in the clinic Or in IND enabling studies, all are a testament to the power of our platform and our approach. We are thrilled in our recent advances and look forward to sharing more details of our clinical development plans in the second half of twenty twenty three. Today, we would like to focus and how we are advancing towards our goal of increasing probability of success within drug discovery and development through an end to end patient centric approach. In our pipeline to date, we have developed precision design compounds with a patient driven data approach in a faster and more efficient way than existing methods. Speaker 200:07:34I'll now hand over to Dave to walk through how we are working towards predicting clinical responses Pre clinically. Speaker 300:07:42Thank you, Andrew. We incorporate the concepts of patient centric drug discovery and development as early as possible in our efforts. Through the use of complex primary patient tissue samples as preclinical models, we are able to leverage our clinically predictive functional imaging platform, especially in translational research. While cell lines and organoid models are scalable and useful in design and development, They do not capture the complexity of actual disease biology, nor do they represent the diversity of patients seen in the clinic. As you can see here on Slide 6, there is a clear difference in the images of the homogeneous cell line compared to the heterogeneous primary patient material we use. Speaker 300:08:26We believe that the heavy use of cell lines as translational models has contributed to the high rate of clinical failure we typically see in our industry. Our answer is to strategically leverage primary patient material for decision making purposes before entering the clinic. By getting as close to the actual patient as possible, we can embrace both the heterogeneity and complexity of disease biology using our patient derived model systems coupled with AI driven technology. In our preclinical studies, We utilized primary material to create complex model systems that better reflect disease and represent patient diversity. These elaborate models are deployed with the goal of identifying indications as well as subpopulations likely to respond to treatment, Uncovering patient enrichment and noninvasive pharmacodynamic biomarkers, understanding the potential for resistance, combination effects and more. Speaker 300:09:27Depending on the program, we take advantage of our precision medicine platform, which has successfully predicted which drugs will work for a given patient as shown in the EXALT study published in cancer discovery in 2021. Functional endpoints in our complex systems allow us to simultaneously quantify what a drug or combination of drugs is doing to cancer, immune and non transformed cells at the single cell level. We can measure anything from cell size to cell death through to pathway activity depending on what we want to quantify. We then combine this functional data with omics readouts from the same patient samples, such as genetic mutations, expression, fusion and transcription events. The omics data provides a molecular understanding of the observed phenotypes. Speaker 300:10:20The union of technologies, Functional and multiomics combined with years of knowledge of how to interpret these datasets in multimodal programs drives a deep understanding of disease biology and population heterogeneity. Exensio's unique proposition is that these data are derived from primary patient samples. This provides a preclinical understanding of how and why a drug is Or just as importantly, is not working in a given patient sample, thus enabling patient enrichment hypothesis generation and the generation of molecular signatures. Today, we will describe 2 ways in which we are combining the use of our functional precision medicine platform with our omics datasets. Once again, an understanding of the effect of adenosine on the cancer microenvironment ahead of the clinical trial in patients and the other for target discovery. Speaker 300:11:15We'll first highlight progress for our 8 0A receptor antagonist 546, which specifically blocks the recognition of adenosine by immune cells within the cancer microenvironment. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment. Adenosine limits the functionality of multiple protective immune infiltrates including T cells, while enhancing the activity of immunosuppressive cell types. Reversing the effects of adenosine driven through the A2A receptor with our antagonist 546 should therefore release the immune system and also help those patients who have become refractory to immune checkpoint inhibition. For patients to benefit from such an approach, 2 critical attributes are required to be present. Speaker 300:12:061, High levels of adenosine in the microenvironment and 2, an immune system primed but suppressed by adenosine. To date, there has been no robust way to measure both immune potential and adenosine levels within the tumor microenvironment. We believe other drug candidates for this target have not achieved clinical success because they failed to enrich for those patients most likely to respond to A2A receptor pathway inhibition. Leveraging our precision medicine platform and scalable in house OBX capabilities, we have identified a patient enrichment biomarker that correlates with adenosine levels in the tumor microenvironment. We call this the adenosine burden score or ABS. Speaker 300:12:53This was found through a detailed examination of multiple primary samples at baseline And after perturbation with adenosine pathway activation. All this work has been done in an effort to maximize the probability of success of 546 in the clinic. On this slide, we show 3 different datasets, 2 from human databases and 1 from mouse data. These include the Cancer Genome Atlas or TCGA and the Reactome database. TCGA is a landmark Cancer genomics program from the National Cancer Institute and National Human Genome Research Institute that characterized at a molecular level Over 20,000 primary cancer and matched normal samples spanning 33 cancer types. Speaker 300:13:40Reactome is an expertly curated to base of biological pathways. At the top in the TCGA dataset when filtering for patients with a high ABS, We observed that these same patient samples are low for published signatures related to inflammation such as the Tumor Inflammation Score or TIS. The TIS has been used to predict anti PD-one efficacy. In the middle panel from the reactome dataset, The ABS anti correlates with the PD-one signaling pathway, indicating that where adenosine is high as measured by the ABS, PD-one signaling is low, thereby nullifying anti PD-one effects. The last chart is an expert curated mouse dataset called TISMO Our tumor immune syngeneic mouse dataset. Speaker 300:14:33This shows that mice considered resistant to checkpoint inhibitor therapy will also enrich for higher mouse ABS, highlighting the rationale for combination therapy in our 546 clinical trial. Taken together, we believe we have discovered a robust specific and sensitive biomarker for adenosine pathway This represents a method for enriching patients likely to respond to our selective adenosine 828 receptor antagonist 546. Comparing the left and right panels, we can see that compared to other disclosed signatures, Ours is much more robust and reproducible across samples. Our signature is comprised mainly of B cell genes towards the later stages of B cell and plasma cell maturation. Similar to that of data from another molecule recently presented at AACR that was discovered retrospectively after a Phase Ib clinical trial. Speaker 300:15:36Our work was done pre clinically and will be validated alongside the IGNITE trial. What we have shown here is that we can generate data ahead of clinical trials using primary patient samples that our peers can only do in the clinical setting. We believe this is a key differentiator for Exensio as we advance additional programs and have implications well beyond our 8 to 8 program. Since our founding, We have aimed to be a learning company with a goal to constantly increase our knowledge from and to reuse all of the data that we produce from discovery through to development. We've just shown you an example of how we can pre clinically identify patient enrichment biomarker hypotheses using a combination of functional and omics data. Speaker 300:16:27I'll now take a moment to highlight how we leverage the same approach in our discovery efforts to understand more about disease biology and target discovery. Using the datasets from preclinical studies, which will be supplemented with information from our clinical and precision medicine studies when available, we can work to understand a disease computationally. I will highlight how we use functional and multi omic data from our primary models to help identify novel targets and druggable pathways for future projects, some of which we believe may help overcome resistance. Here we show an overview of some of the data inputs we use to triangulate and prioritize novel targets. We start with our proprietary data from various programs that take advantage of our functional precision medicine platform And next generation sequencing unit. Speaker 300:17:20All of this data is from patient tissue models and this differentiates our approach from others. We then combine this with well annotated public data such as known drug to target annotations taking into account the drug's polypharmacology And protein protein interactions in a custom unified and extensible computational framework. While the use cases of a program that captures the complexity of a disease in silico are vast, the example I want to describe today is focused on target identification. Our patient centric multi omic platform has the potential to uncover targets with high clinical relevance at the discovery stage as well as support target validation and biomarker discovery. At the bottom of the slide, we see our functional layer of data, target annotations and the interactome come together to prioritize targets using drug sensitivity and protein protein interactions as a guide to identify convergent targets. Speaker 300:18:22Here we put everything together. I want to first show you a diagram of how this data is represented. We use our precision medicine platform to collect functional and multiomics data from patient tissues in combination with proprietary methodology for multi omic and multimodal dataset mapping. Then we integrate it using our computational framework. The outer layer represents the standard of care drugs we use as tools to probe the potential target landscape. Speaker 300:18:53Drugs are connected to their known targets, including off targets on the next layer. Finally, known targets are embedded in the curated Protein protein interaction network allowing us to identify novel targets at the focal points of successful therapies. More than that, we are also able to corroborate and refine our findings using a rich layer of multiomics data such as phosphoproteomics and single cell RNA Seq generated under treatment conditions from the same samples. This approach has the potential to uncover targets with high clinical relevance at the discovery stage and lead to improved patient outcomes. What you see here is an example functional screen performed in 20 ovarian cancer patient tissue samples. Speaker 300:19:42We wanted to understand the cancer specific cytotoxic effect of drugs with well annotated targets. You may recognize this data from one of our recent AACR posters. On the left, we have identified numerous novel sensitivities to a subset of tyrosine kinase inhibitors or TKIs signified by large dark purple circles within a subset of samples. What's important to appreciate here is that the effects we observe for many drugs in patient tissues, the left panel, are not recapitulated in publicly available cell line sensitivity data indicated on the right. This demonstrates how the use of cell lines and other cultured model systems may obscure targetable pathways. Speaker 300:20:29This is likely due to oversimplification of tumor biology since the cell lines lack a complex and diverse cancer environment. Instead, our primary model system incorporates multiple cell types and avoids immortalization or amplification in order to better capture the complex biology of the original microenvironment. But what this does not yet tell us is why specific drugs are having an effect and what they have in common, complicated by the fact that many of them have known polypharmacologies. Overlaying our unique functional endpoints with multiomics data, we use drugs as tools while also mapping sensitive and insensitive pathways across multiple molecular layers and begin to reveal novel biology and target spaces. So here we show the actual data with the targets blinded. Speaker 300:21:24First, we use network integration of patient tissue functional data to triangulate convergent targets. Then we add a layer of data from multiomics measurements that lets us further prioritize them by Such as disease specific expression, mutation profiles or novelty. The diagram from outer to inner circle Shows firstly global compound sensitivities, then known primary targets, and finally, predicted downstream targets. These targets are not impacted by community bias highlighting 1st in class potential. Keep in mind, this is data from real patient samples, grounding us in complex human biology. Speaker 300:22:08This means that we can combine real time multiomics data With the functional biology readouts to directly measure drug response from multiple angles on every sample. This helps us identify novel targets with demonstrated We already have some targets identified from this approach going through tractability and validation internally, And we look forward to keeping you updated on our truly differentiated platform. As I mentioned earlier, Exensio is a learning company, Not just in practice, but also through the reuse and redeployment of collected disease modeling datasets. Here we use a functional profiling as a guide to build computational disease models for Target ID. We are also working to redeploy data for target validation, VASTA patient enrichment biomarker discovery and combination prediction. Speaker 300:23:06We've provided examples here on how complex disease relevant models Combined with a smart analysis and interpretation of many levels of big data can reveal mechanisms of adenosine pathway activation for us to identify patients that may be sensitive to 546 treatment. They're also working on predicting combinations and identifying resistance breaking characteristics for our CDK7 inhibitor 617. We plan to present 617 data towards the end of this year and we'll be adding more data to these models as our pipeline grows and as we recruit patients into our clinical studies. And with that, I will now turn the call over to Ben to walk through financial highlights. Speaker 400:23:49Thank you, Dave. Speaker 500:23:51I'll now take a minute to close with highlights from our financial results. Full results are detailed in our press release and Form Okay. I'll review the results in U. S. Dollars using the March 31, 2023 constant currency rate of $1.24 to the pound. Speaker 500:24:10We ended the quarter with $553,300,000 in cash, equivalents And bank deposits. We believe this provides us with several years of cash runway and the resources to continue investing in our growth. As Andrew noted earlier, we continue to successfully advance our internal and partner projects. At the same time, we have also been executing cost efficiency programs that are expected to save over $20,000,000 during the course of 2023 and more in 2024. This has been a combination of automation through technology and narrowing the focus of our operations on core activities that have a differentiated commercial profile. Speaker 500:24:51We remain cautious in the current macroeconomic environment and intend to continue our cost control efforts through the end of the year with a focus on optimizing workflows and automation. We have a robust business development dialogue and maintain our guidance of Two new deals this year. Earlier in the year, many of the large pharma had substantially slowed their decision making process for new partnerships as they conducted pipeline reductions and budget cuts in response to the IRA and other well noted industry trends. Recently, we have seen a renewed energy and excitement from our potential partners, especially in our core technologies such as personalized medicine In generative AI. It is important to note that we have never stopped investing in new technologies. Speaker 500:25:40While we are being intelligent about burn rate, we continue to see substantial technology advancements even on a quarter to quarter basis. Dave discussed how we had taken a strong phenotypic translational platform and invested to add multimodal data that now can produce personalized cellular signatures at every stage of discovery and development. And this is only one example of our growth. We have over 200 people in our technology group focused on improving the capabilities and predictive powering of our AI across the company. This is how we intend to stay in our current leadership position. Speaker 500:26:17And with that, I will turn the call back over to Andrew. Speaker 200:26:21Thank you, Ben. During our presentation today, we've highlighted the progress of our clinical and preclinical programs. We are bringing new molecules into the clinic and building out our AI powered precision medicine platform. We are confident that our differentiated tech enabled approach will yield strong outcomes. To finish, let me add just how proud I am to lead a global team This talented and determined will help us do everything in our power to deliver on Exensio's promise to transform the way the industry discovers and develops Effective medicines and to deliver the best possible outcomes to as many people as possible around the world. Speaker 200:27:04With that, we'll open up the call for questions. Operator00:27:08Thank you. Our first question is from Alex Stranahan with Bank of America. Your line is open. Speaker 400:27:20Hi, guys. Thanks for taking our questions. I have Two higher level ones. I saw an interesting quote, I think, from Gary that by the end of this decade, design of all new drug candidates will be augmented by AI, what do you see as being the key points that need to be addressed today for this future to be realized either at the basic science level programming Or regulatory levels. And as a follow-up to that, maybe for Andrew, how does a company such as Yes, drive the most value for shareholders. Speaker 400:27:51If this is the direction that the industry is going, is it through more design as a service such as your Speaker 600:28:07Thank you so much for excellent questions, Alex. Really great actually and very topical point as well. Actually, for the first question, as you did actually direct that to Gary, I'm actually going to have Gary to have outlined as CTO what he sees actually as sort of the key Further challenges really expand AI's use in pharma for all drugs eventually to be designed by AI. Gary? Speaker 700:28:31Cool. Yes. Thanks, Andrew. I think I mean, the first thing is we're incredibly proud We've now enabled 6 clinical candidates using AI. And that kind of really shows the promise of the power. Speaker 700:28:45And you've only got to pick up a newspaper or look anywhere really to see how the entire world and the entire world of drug discovery is starting to Embrace the use of artificial intelligence and broader computational methods. So I think there is a natural evolution. I think for us, what's really important to us is how do we stay at the forefront of that. And I think the activities that Exensio is Building out at the moment, particularly in linking AI design to physical automation, robotics and assist robotic Screening is really closing the cycle and enabling us to drive our projects even more quickly in the future. So I think it's developments like this that are going to enable more broad acceptance and utilization of these kind of technologies in drug discovery. Speaker 700:29:36And this field has to be a fantastic thing, doesn't it? You really want to bring medicines to patients faster and more effectively as we're demonstrating technology can do. Speaker 600:29:46Thank you, Gary. Really want to underline Gary's answer actually in how we think about things. To answer your second part of the question, Alex, the way we think about it is that we're incredibly pleased to see that sort of our DesignPro S now and bring in 6 molecules have used generative AI approaches now into the clinic. As you said, actually, the latest Actually being with Dynap and Sumitomo Pharma, which was with an earlier business model called Design as a Service. We're always open to doing many kinds of deals structures, as you've seen, actually, I think our business development prowess over the past few years has actually shown that. Speaker 600:30:21But the way we see that AI is going to create real value is to think about what that product of the future looks like, what that sort of AI enabled drug starts look like. What we see as the hallmark on Exensio drug is a drug that uses advanced compute, Machine learning, AI and physics based methods to design precision design, the high quality molecule, but also venues in our deep learning multimodal approaches that Dave was talking Earlier to really define the patient selection strategy, bringing those 2 together in a model driven adaptive learning approach to learn about the drug. That's what we see. So it's 2 pieces of key IP, the molecule being designed by AI and using AI event to design the biomarker. Voice coming together is what we think is the hallmark of Exensio drug, and that's where we believe in the long term, the high value wealth can be created By effectively creating highly effective medicines with high response by actually designing the best molecule and targeting the right patients. Operator00:31:27The next question is from Vitram Pure Head with Morgan Stanley. Your line is open. Speaker 800:31:32Hi. Thanks for taking our question. This is Steve for Baikung. So I want to ask about the A2A program. Could you Discuss the prior treatment history for the patient you are enrolling into the trial? Speaker 800:31:43And when can we expect to see the initial data? And what's your expectation about The readout. Thank you. Speaker 600:31:51Thank you very much, Steve. For that question, actually, I want to hand the stage over to Mike Kramm, our Chief Quantitative Medicine Officer, who's actually leading our clinical development work here. Mike? Speaker 900:32:03Yes. Thank you very much for the question. So we have recruited our first patient into this program. It's a Phase onetwo study. And we use simulation guided clinical trial design to come up with an approach where we initially have a dose escalation, Aiming to make the correct decision at the earliest time point as to what the dose and treatment regimen is that we will take into a dose expansion phase. Speaker 900:32:29We're going to learn about the operating characteristics of the investigational compound. But at the same time, We are qualifying the adenosine burden score, as Andrew pointed out, as our tool to identify Which are the correct patients who might benefit from an A2A receptor antagonist in conjunction with a checkpoint inhibitor? As to when data will become available, this is a Phase III study in early development in oncology as many others. So it's really very similar to other programs and we are going to provide further guidance as time progresses. Operator00:33:19The next question is from Peter Lawson with Barclays. Your line is open. Peter Lawson with Barclays. Your line is open. Please go ahead. Operator00:33:35We will move on to the next question, which is from Chris Shibutani with Goldman Sachs. Your line is open. Speaker 1000:33:43Hi. It's Roger on for Chris. Just a quick question on 565, the MALT1 inhibitor. You're likely aware that J and J, they debut their Phase 1 data for their MULT1 inhibitor in NHL and CLL. I was just wondering if you'd comment a little bit on the inhibition of UGT1A1 and where do you expect 5 5 to come out in terms of differentiation, noting the competitive landscape. Speaker 1000:34:09Thanks. Speaker 600:34:11Thank you much, Roger. So Great question, actually. It's been a key point of how we have been designed a differentiated molecule. I'm actually going to hand this question over to Dave Hallett, our Chief Scientific Officer, To give you some more color on it. Speaker 1100:34:24Thank you, Anjou. And thank you for the question. I think the publication of the abstract, I think, is coming out Head of a European Oncology Symposium was very timely. So if you recollect the information that we put out Very recently around the design criteria around our MORT1 inhibitor and specifically the topic of Hyperbilirubinemia and driven by inhibition of UGT101. If you remember the takeaway story from those that We strongly believe that our molecule is differentiated from J and J and most likely quite a few other competitor molecules And that it has little to no activity at that particular transporter and is therefore likely unlikely to drive that particular side effect. Speaker 1100:35:14If you actually look into even into the abstract details, it's pretty apparent from J and J, as we would have predicted, that they do see hyperbiliary anemia in the clinic. They've had to take account of that in their recommended Phase 2 dose. I'm sure they would have preferred not to have done that. And So I think we stand by, I think that original assertion is that that was a really important differentiation criteria. I think it will our molecule, we believe, should be free of that particular Potential toxicity. Speaker 1100:35:47And more importantly, as I think as we highlighted is that, when asked to remember, it's very likely that a MOLT-one inhibitor will be used in combination with other agents like BTK inhibitors. And therefore, you need as clear as possible a safety profile so that you could dose that molecule as high as possible. So, no, it was I think it was I wish J and J well. I think obviously as they take that compound forward into patient studies, but I think it supported our notion about the differentiation angle of our own compound. Speaker 1000:36:20Thank Speaker 700:36:21you. The Operator00:36:23next question is from Peter Lawson with Barclays. Your line is open. Speaker 1200:36:28Hi, this is Shay on for Peter. Thanks so much for taking my question. Just wanted to touch base on the biologic side of your platform and maybe some progress And how you're thinking about balancing your biologics versus small molecule development and maybe even when we could see the first antibody program going into the clinic? Thanks so much. Speaker 600:36:44Excellent. Thank you very much. I'm going to hand over this question actually to Gary, who's in team has the algorithms for developing sort of biologics by design Speaker 700:36:58Gary? Yes. Thanks. And thanks for the question. And we mean, we're really excited about the way that we can introduce Biologics into our AI design platform and Professor Shailat, Dean has been working to build out the algorithms and all the technology to actually drive that forward. Speaker 700:37:16We're still at the point where we're developing a robust process and we're starting to run our 1st pilot project. So I think we're a little bit away from talking about a molecule in the clinic right now. But what I can tell you is we are developing actually, I'd say, world leading capabilities in the areas of Predicting structure and being able to do generative design into the antibody space. Speaker 600:37:42In terms of growing the pipeline, we certainly are now looking to think about how we might bring forward sort of our first programs going at and actually how then we start to map then of The antibodies, the capabilities we've been building actually to sort of our key of therapeutic areas sort of focus. One exciting thing is that we've already demonstrated Is that our precision medicine platform actually also works antibodies as well as small molecules. And that's a key thing then, because it allows us then to think about How then as we head towards the clinic, we could also bring to bear our precision medicine technology. And I think that's going to bring a unique differentiator as well actually in this particular Operator00:38:31The next question is from Steve with Morgan Stanley. Your line is open. Speaker 400:38:37Good morning, everyone. This is Gaspar on for Vikram. I have Speaker 900:38:41a question regarding your PKC program. So for the PKC data program in partnership with BMS, I was wondering how much visibility and control do you have Now into the path forward for this molecule and how it might progress through early stage development? Thank you. Speaker 1100:39:00So this is Dave Hallett. Thank you for that question. So in terms of public visibility, because BMS in license that particular program, they both now control the clinical development of that project, But also, obviously, kind of public disclosures that are related to that. As a trusted partner and partner of the GSE, we will receive kind of updates on that program ourselves. But just to reiterate to everyone who's on the call is that that particular asset It's begun a healthy human volunteer study in the United States in the early part of this year, and we look forward to kind of receiving updates from BMS as they progress. Operator00:39:50We have no further questions at this time. We'll turn it back to the presenters for any closing remarks. Speaker 600:39:56Thank you, Chris. As Exensia's CEO and Founder, I am proud to see our company maturing into an end to end precision medicines business spanning from discovery Into early development and supported at each stage by our innovative technology platforms. Our goal is to be as innovative in the clinic As we have been in discovery, our remarkable progress to date is a testament to the strength of the company. Thank you to everyone today on the call Thank you. Thank you. Speaker 600:40:31Operator, you may now disconnect. Operator00:40:35Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.Read morePowered by Conference Call Audio Live Call not available Earnings Conference CallExscientia Q1 202300:00 / 00:00Speed:1x1.25x1.5x2x Earnings DocumentsSlide DeckPress Release(8-K) Exscientia Earnings HeadlinesExscientia and Recursion Merge to Revolutionize Drug DiscoveryNovember 21, 2024 | markets.businessinsider.comRecursion, Exscientia officially combine to advance drug discoveryNovember 21, 2024 | markets.businessinsider.comThe collapse has already startedThe headlines scream tariffs and export bans — but the real damage is happening in retirement portfolios. Tim Plaehn reveals how the 2025 trade war is quietly eroding dividend income — and which U.S.-focused stocks are still raising payouts.May 1, 2025 | Investors Alley (Ad)Recursion: No News Isn't Good News When It Comes To Vanilla PipelineNovember 20, 2024 | seekingalpha.comBarclays Sticks to Its Hold Rating for Exscientia Plc (EXAI)November 15, 2024 | markets.businessinsider.comRecursion and Exscientia Merger Approved by ShareholdersNovember 14, 2024 | markets.businessinsider.comSee More Exscientia Headlines Get Earnings Announcements in your inboxWant to stay updated on the latest earnings announcements and upcoming reports for companies like Exscientia? Sign up for Earnings360's daily newsletter to receive timely earnings updates on Exscientia and other key companies, straight to your email. Email Address About ExscientiaExscientia (NASDAQ:EXAI), an artificial intelligence (AI) driven Pharma-tech company, engages in design and develop differentiated medicines for diseases with high unmet patient needs. The company's lead product candidate GTAEXS617, a CDK7 inhibitor, which is currently in a Phase 1/2 trial to manage the potential toxicities associated with CDK7 as well as optimizing pharmacokinetics for maximizing on-target efficacy. It is also involved in the development of EXS4318, a PKC-theta inhibitor, under Phase 1 clinical trial for inflammation and immunology indications; EXS74539, a LSD1 inhibitor, under preclinical studies for SCLC, AML, and potential additional indications; EXS73565, a MALT1 inhibitor, under preclinical studies for multiple hematology indications; and DSP-0038, currently in Phase 1 studies. The company has collaboration agreements with Merck KGaA, Bristol Myers Squibb, Sanofi, Bill & Melinda Gates Foundation, Charité Universitätsmedizin Berlin, Rallybio, and GT Apeiron Therapeutics. 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There are 13 speakers on the call. Operator00:00:00Hello, everyone. My name is Chris, and I'll be your conference operator today. At this time, I'd like to welcome everyone to Exensio's Business Update Call for the Q1 2023. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. Operator00:00:28At this time, I would like to introduce Sarah Sherman, Vice President of Investor Relations. Sarah, you may begin. Speaker 100:00:36Thank you, operator. A press release and 6 ks were issued this morning with our Q1 2023 financial results and business update. These documents can be found on our website at www.investors. Exensia.ai, along with the presentation for today's webcast. Before we begin, I'd like to remind you that we may make forward looking statements on our call. Speaker 100:01:00These may include statements about our projected growth, revenue, business models, preclinical and clinical results and business performance. Actual results may differ materially from those indicated by these statements. Unless required by law, Exensia does not undertake any obligation to update these statements regarding the future or to confirm these statements in relation to actual results. On today's call, I'm joined by Andrew Hopkins, Chief Executive Officer Dave Hallett, Chief Scientific Officer and Ben Taylor, CFO and Chief Strategy Officer Gary Perito, Chief Technology Officer and Mike Kremz, Chief Quantitative Medicine Officer, will also be available for the Q and A session. And with that, I will now turn the call over to Andrew. Speaker 200:01:47Thank you, Sarah. Today, we're going to talk about a differentiated approach to personalized medicine, how we use complex, primary patient tissue samples as preclinical models. Combining this with our in house multiormous capabilities, we can go from target identification all the way through to the clinic. 2023 is off to an exciting start as we continue to advance our pipeline and strengthen our business. We've made significant progress across our internal and Partner programs include an advancing 2 molecules into the clinic, EXS-four thousand three hundred and eighteen and EXS-two thousand one hundred and fifty six. Speaker 200:02:24An additional molecule, DSP-two thousand three hundred and forty two was advanced by Sumitomo Pharma, which was a result of an early collaboration with Exensio but is now complete. This marks our 6 novel molecule created for Exensia's generative AI platform to enter the clinical stage. We've expanded our precision oncology pipeline by initiating IND enabling programs for 74,00539, an LSD1 inhibitor and EXS-seventy three thousand five hundred and sixty five, a MULT1 protease inhibitor. More recently, we presented multiple posters of the AACR Annual Meeting, highlighting research that continues to validate our end to end approach and demonstrates the potential of a platform to rapidly advance high quality drug candidates towards the clinic. Our team's commitment to strong execution has enabled us to rapidly move programs from discovery through to the clinic. Speaker 200:03:19We have achieved a number of milestones already this year. In March, we announced 2 new wholly owned precision design molecules, an LSC1 inhibitor, 539, and a multi-one inhibitor, 565. Both programs continue to progress through IND enabling studies. We expect to provide an update on clinical development plans in the second half of this year. We remain on track to meet our target of 4 candidates with meaningful economics for Exensia in clinical development by 2024. Speaker 200:03:48In February, Bristol Myers Squibb initiated the 1st in human study of EXS-four thousand three hundred and eighteen, our potential 1st in class selective PKC Theta inhibitor, 4318, was designed by Exensia and is currently in Phase 1 clinical trials in the United States. Earlier this month, the first patient was dosed in IGNITE, our Phase onetwo trial evaluating EXS-two thousand one hundred and fifty six or 546, Our A2A receptor antagonist. This was the 1st AI designed immuno oncology drug in the clinic And we remain on track to dose the 1st patient in a Phase onetwo study of GTA EXS-six seventeen, our precision designed CDK7 inhibitor co owned with GTI Paragon in the coming weeks. We also remain well capitalized with $553,000,000 In cash at the end of the quarter, this provides us with several years runway to advance our near term programs without the need to raise external capital. On today's call, we'd like to provide more detail on our approach of combining precision design with personalized medicine. Speaker 200:04:58Before handing over to Dave Hallett, our CSO, I want to highlight a recent scientific presence at this year's AACR meeting. We presented data further validating our ability to efficiently design high quality drug candidates and to identify and predict the right patient populations that may benefit the most from treatment. Firstly, for 546, we presented research on our adenosine burden score or ABS. It showed that 506 reverses the effect of adenosine analogs ex vivo in patient tissue samples and other complex models. The ABS has been validated in our ongoing IGNITE Phase III clinical study of 546 and will be discussed further today. Speaker 200:05:42Ignite was designed based on extensive simulations to enable the most effective continuous reassessment method settings to predict and accurately evaluate The anti tumor effects of 546 in combination with checkpoint inhibition. The team also presented preclinical data On EXS-seventy four thousand five hundred and thirty nine, our precision designed LST1 inhibitor. We designed 539 to optimally target LST1 in future Oncology and hematological patient populations. These preclinical data demonstrate that 5C9 has the potential to Lastly, we highlighted the benefits of using data generated with Exensio's Precision Medicine platform in combination with its Proprietary methodology for multi omics and multimobile mapping. By better understanding disease mechanisms, These tools combined can be leveraged to improve patient outcomes by uncovering clinically relevant drug targets already at the discovery stage. Speaker 200:06:50We will go into more depth in this topic shortly. In summary, we have 5 programs of economics that are either in the clinic Or in IND enabling studies, all are a testament to the power of our platform and our approach. We are thrilled in our recent advances and look forward to sharing more details of our clinical development plans in the second half of twenty twenty three. Today, we would like to focus and how we are advancing towards our goal of increasing probability of success within drug discovery and development through an end to end patient centric approach. In our pipeline to date, we have developed precision design compounds with a patient driven data approach in a faster and more efficient way than existing methods. Speaker 200:07:34I'll now hand over to Dave to walk through how we are working towards predicting clinical responses Pre clinically. Speaker 300:07:42Thank you, Andrew. We incorporate the concepts of patient centric drug discovery and development as early as possible in our efforts. Through the use of complex primary patient tissue samples as preclinical models, we are able to leverage our clinically predictive functional imaging platform, especially in translational research. While cell lines and organoid models are scalable and useful in design and development, They do not capture the complexity of actual disease biology, nor do they represent the diversity of patients seen in the clinic. As you can see here on Slide 6, there is a clear difference in the images of the homogeneous cell line compared to the heterogeneous primary patient material we use. Speaker 300:08:26We believe that the heavy use of cell lines as translational models has contributed to the high rate of clinical failure we typically see in our industry. Our answer is to strategically leverage primary patient material for decision making purposes before entering the clinic. By getting as close to the actual patient as possible, we can embrace both the heterogeneity and complexity of disease biology using our patient derived model systems coupled with AI driven technology. In our preclinical studies, We utilized primary material to create complex model systems that better reflect disease and represent patient diversity. These elaborate models are deployed with the goal of identifying indications as well as subpopulations likely to respond to treatment, Uncovering patient enrichment and noninvasive pharmacodynamic biomarkers, understanding the potential for resistance, combination effects and more. Speaker 300:09:27Depending on the program, we take advantage of our precision medicine platform, which has successfully predicted which drugs will work for a given patient as shown in the EXALT study published in cancer discovery in 2021. Functional endpoints in our complex systems allow us to simultaneously quantify what a drug or combination of drugs is doing to cancer, immune and non transformed cells at the single cell level. We can measure anything from cell size to cell death through to pathway activity depending on what we want to quantify. We then combine this functional data with omics readouts from the same patient samples, such as genetic mutations, expression, fusion and transcription events. The omics data provides a molecular understanding of the observed phenotypes. Speaker 300:10:20The union of technologies, Functional and multiomics combined with years of knowledge of how to interpret these datasets in multimodal programs drives a deep understanding of disease biology and population heterogeneity. Exensio's unique proposition is that these data are derived from primary patient samples. This provides a preclinical understanding of how and why a drug is Or just as importantly, is not working in a given patient sample, thus enabling patient enrichment hypothesis generation and the generation of molecular signatures. Today, we will describe 2 ways in which we are combining the use of our functional precision medicine platform with our omics datasets. Once again, an understanding of the effect of adenosine on the cancer microenvironment ahead of the clinical trial in patients and the other for target discovery. Speaker 300:11:15We'll first highlight progress for our 8 0A receptor antagonist 546, which specifically blocks the recognition of adenosine by immune cells within the cancer microenvironment. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment. Adenosine limits the functionality of multiple protective immune infiltrates including T cells, while enhancing the activity of immunosuppressive cell types. Reversing the effects of adenosine driven through the A2A receptor with our antagonist 546 should therefore release the immune system and also help those patients who have become refractory to immune checkpoint inhibition. For patients to benefit from such an approach, 2 critical attributes are required to be present. Speaker 300:12:061, High levels of adenosine in the microenvironment and 2, an immune system primed but suppressed by adenosine. To date, there has been no robust way to measure both immune potential and adenosine levels within the tumor microenvironment. We believe other drug candidates for this target have not achieved clinical success because they failed to enrich for those patients most likely to respond to A2A receptor pathway inhibition. Leveraging our precision medicine platform and scalable in house OBX capabilities, we have identified a patient enrichment biomarker that correlates with adenosine levels in the tumor microenvironment. We call this the adenosine burden score or ABS. Speaker 300:12:53This was found through a detailed examination of multiple primary samples at baseline And after perturbation with adenosine pathway activation. All this work has been done in an effort to maximize the probability of success of 546 in the clinic. On this slide, we show 3 different datasets, 2 from human databases and 1 from mouse data. These include the Cancer Genome Atlas or TCGA and the Reactome database. TCGA is a landmark Cancer genomics program from the National Cancer Institute and National Human Genome Research Institute that characterized at a molecular level Over 20,000 primary cancer and matched normal samples spanning 33 cancer types. Speaker 300:13:40Reactome is an expertly curated to base of biological pathways. At the top in the TCGA dataset when filtering for patients with a high ABS, We observed that these same patient samples are low for published signatures related to inflammation such as the Tumor Inflammation Score or TIS. The TIS has been used to predict anti PD-one efficacy. In the middle panel from the reactome dataset, The ABS anti correlates with the PD-one signaling pathway, indicating that where adenosine is high as measured by the ABS, PD-one signaling is low, thereby nullifying anti PD-one effects. The last chart is an expert curated mouse dataset called TISMO Our tumor immune syngeneic mouse dataset. Speaker 300:14:33This shows that mice considered resistant to checkpoint inhibitor therapy will also enrich for higher mouse ABS, highlighting the rationale for combination therapy in our 546 clinical trial. Taken together, we believe we have discovered a robust specific and sensitive biomarker for adenosine pathway This represents a method for enriching patients likely to respond to our selective adenosine 828 receptor antagonist 546. Comparing the left and right panels, we can see that compared to other disclosed signatures, Ours is much more robust and reproducible across samples. Our signature is comprised mainly of B cell genes towards the later stages of B cell and plasma cell maturation. Similar to that of data from another molecule recently presented at AACR that was discovered retrospectively after a Phase Ib clinical trial. Speaker 300:15:36Our work was done pre clinically and will be validated alongside the IGNITE trial. What we have shown here is that we can generate data ahead of clinical trials using primary patient samples that our peers can only do in the clinical setting. We believe this is a key differentiator for Exensio as we advance additional programs and have implications well beyond our 8 to 8 program. Since our founding, We have aimed to be a learning company with a goal to constantly increase our knowledge from and to reuse all of the data that we produce from discovery through to development. We've just shown you an example of how we can pre clinically identify patient enrichment biomarker hypotheses using a combination of functional and omics data. Speaker 300:16:27I'll now take a moment to highlight how we leverage the same approach in our discovery efforts to understand more about disease biology and target discovery. Using the datasets from preclinical studies, which will be supplemented with information from our clinical and precision medicine studies when available, we can work to understand a disease computationally. I will highlight how we use functional and multi omic data from our primary models to help identify novel targets and druggable pathways for future projects, some of which we believe may help overcome resistance. Here we show an overview of some of the data inputs we use to triangulate and prioritize novel targets. We start with our proprietary data from various programs that take advantage of our functional precision medicine platform And next generation sequencing unit. Speaker 300:17:20All of this data is from patient tissue models and this differentiates our approach from others. We then combine this with well annotated public data such as known drug to target annotations taking into account the drug's polypharmacology And protein protein interactions in a custom unified and extensible computational framework. While the use cases of a program that captures the complexity of a disease in silico are vast, the example I want to describe today is focused on target identification. Our patient centric multi omic platform has the potential to uncover targets with high clinical relevance at the discovery stage as well as support target validation and biomarker discovery. At the bottom of the slide, we see our functional layer of data, target annotations and the interactome come together to prioritize targets using drug sensitivity and protein protein interactions as a guide to identify convergent targets. Speaker 300:18:22Here we put everything together. I want to first show you a diagram of how this data is represented. We use our precision medicine platform to collect functional and multiomics data from patient tissues in combination with proprietary methodology for multi omic and multimodal dataset mapping. Then we integrate it using our computational framework. The outer layer represents the standard of care drugs we use as tools to probe the potential target landscape. Speaker 300:18:53Drugs are connected to their known targets, including off targets on the next layer. Finally, known targets are embedded in the curated Protein protein interaction network allowing us to identify novel targets at the focal points of successful therapies. More than that, we are also able to corroborate and refine our findings using a rich layer of multiomics data such as phosphoproteomics and single cell RNA Seq generated under treatment conditions from the same samples. This approach has the potential to uncover targets with high clinical relevance at the discovery stage and lead to improved patient outcomes. What you see here is an example functional screen performed in 20 ovarian cancer patient tissue samples. Speaker 300:19:42We wanted to understand the cancer specific cytotoxic effect of drugs with well annotated targets. You may recognize this data from one of our recent AACR posters. On the left, we have identified numerous novel sensitivities to a subset of tyrosine kinase inhibitors or TKIs signified by large dark purple circles within a subset of samples. What's important to appreciate here is that the effects we observe for many drugs in patient tissues, the left panel, are not recapitulated in publicly available cell line sensitivity data indicated on the right. This demonstrates how the use of cell lines and other cultured model systems may obscure targetable pathways. Speaker 300:20:29This is likely due to oversimplification of tumor biology since the cell lines lack a complex and diverse cancer environment. Instead, our primary model system incorporates multiple cell types and avoids immortalization or amplification in order to better capture the complex biology of the original microenvironment. But what this does not yet tell us is why specific drugs are having an effect and what they have in common, complicated by the fact that many of them have known polypharmacologies. Overlaying our unique functional endpoints with multiomics data, we use drugs as tools while also mapping sensitive and insensitive pathways across multiple molecular layers and begin to reveal novel biology and target spaces. So here we show the actual data with the targets blinded. Speaker 300:21:24First, we use network integration of patient tissue functional data to triangulate convergent targets. Then we add a layer of data from multiomics measurements that lets us further prioritize them by Such as disease specific expression, mutation profiles or novelty. The diagram from outer to inner circle Shows firstly global compound sensitivities, then known primary targets, and finally, predicted downstream targets. These targets are not impacted by community bias highlighting 1st in class potential. Keep in mind, this is data from real patient samples, grounding us in complex human biology. Speaker 300:22:08This means that we can combine real time multiomics data With the functional biology readouts to directly measure drug response from multiple angles on every sample. This helps us identify novel targets with demonstrated We already have some targets identified from this approach going through tractability and validation internally, And we look forward to keeping you updated on our truly differentiated platform. As I mentioned earlier, Exensio is a learning company, Not just in practice, but also through the reuse and redeployment of collected disease modeling datasets. Here we use a functional profiling as a guide to build computational disease models for Target ID. We are also working to redeploy data for target validation, VASTA patient enrichment biomarker discovery and combination prediction. Speaker 300:23:06We've provided examples here on how complex disease relevant models Combined with a smart analysis and interpretation of many levels of big data can reveal mechanisms of adenosine pathway activation for us to identify patients that may be sensitive to 546 treatment. They're also working on predicting combinations and identifying resistance breaking characteristics for our CDK7 inhibitor 617. We plan to present 617 data towards the end of this year and we'll be adding more data to these models as our pipeline grows and as we recruit patients into our clinical studies. And with that, I will now turn the call over to Ben to walk through financial highlights. Speaker 400:23:49Thank you, Dave. Speaker 500:23:51I'll now take a minute to close with highlights from our financial results. Full results are detailed in our press release and Form Okay. I'll review the results in U. S. Dollars using the March 31, 2023 constant currency rate of $1.24 to the pound. Speaker 500:24:10We ended the quarter with $553,300,000 in cash, equivalents And bank deposits. We believe this provides us with several years of cash runway and the resources to continue investing in our growth. As Andrew noted earlier, we continue to successfully advance our internal and partner projects. At the same time, we have also been executing cost efficiency programs that are expected to save over $20,000,000 during the course of 2023 and more in 2024. This has been a combination of automation through technology and narrowing the focus of our operations on core activities that have a differentiated commercial profile. Speaker 500:24:51We remain cautious in the current macroeconomic environment and intend to continue our cost control efforts through the end of the year with a focus on optimizing workflows and automation. We have a robust business development dialogue and maintain our guidance of Two new deals this year. Earlier in the year, many of the large pharma had substantially slowed their decision making process for new partnerships as they conducted pipeline reductions and budget cuts in response to the IRA and other well noted industry trends. Recently, we have seen a renewed energy and excitement from our potential partners, especially in our core technologies such as personalized medicine In generative AI. It is important to note that we have never stopped investing in new technologies. Speaker 500:25:40While we are being intelligent about burn rate, we continue to see substantial technology advancements even on a quarter to quarter basis. Dave discussed how we had taken a strong phenotypic translational platform and invested to add multimodal data that now can produce personalized cellular signatures at every stage of discovery and development. And this is only one example of our growth. We have over 200 people in our technology group focused on improving the capabilities and predictive powering of our AI across the company. This is how we intend to stay in our current leadership position. Speaker 500:26:17And with that, I will turn the call back over to Andrew. Speaker 200:26:21Thank you, Ben. During our presentation today, we've highlighted the progress of our clinical and preclinical programs. We are bringing new molecules into the clinic and building out our AI powered precision medicine platform. We are confident that our differentiated tech enabled approach will yield strong outcomes. To finish, let me add just how proud I am to lead a global team This talented and determined will help us do everything in our power to deliver on Exensio's promise to transform the way the industry discovers and develops Effective medicines and to deliver the best possible outcomes to as many people as possible around the world. Speaker 200:27:04With that, we'll open up the call for questions. Operator00:27:08Thank you. Our first question is from Alex Stranahan with Bank of America. Your line is open. Speaker 400:27:20Hi, guys. Thanks for taking our questions. I have Two higher level ones. I saw an interesting quote, I think, from Gary that by the end of this decade, design of all new drug candidates will be augmented by AI, what do you see as being the key points that need to be addressed today for this future to be realized either at the basic science level programming Or regulatory levels. And as a follow-up to that, maybe for Andrew, how does a company such as Yes, drive the most value for shareholders. Speaker 400:27:51If this is the direction that the industry is going, is it through more design as a service such as your Speaker 600:28:07Thank you so much for excellent questions, Alex. Really great actually and very topical point as well. Actually, for the first question, as you did actually direct that to Gary, I'm actually going to have Gary to have outlined as CTO what he sees actually as sort of the key Further challenges really expand AI's use in pharma for all drugs eventually to be designed by AI. Gary? Speaker 700:28:31Cool. Yes. Thanks, Andrew. I think I mean, the first thing is we're incredibly proud We've now enabled 6 clinical candidates using AI. And that kind of really shows the promise of the power. Speaker 700:28:45And you've only got to pick up a newspaper or look anywhere really to see how the entire world and the entire world of drug discovery is starting to Embrace the use of artificial intelligence and broader computational methods. So I think there is a natural evolution. I think for us, what's really important to us is how do we stay at the forefront of that. And I think the activities that Exensio is Building out at the moment, particularly in linking AI design to physical automation, robotics and assist robotic Screening is really closing the cycle and enabling us to drive our projects even more quickly in the future. So I think it's developments like this that are going to enable more broad acceptance and utilization of these kind of technologies in drug discovery. Speaker 700:29:36And this field has to be a fantastic thing, doesn't it? You really want to bring medicines to patients faster and more effectively as we're demonstrating technology can do. Speaker 600:29:46Thank you, Gary. Really want to underline Gary's answer actually in how we think about things. To answer your second part of the question, Alex, the way we think about it is that we're incredibly pleased to see that sort of our DesignPro S now and bring in 6 molecules have used generative AI approaches now into the clinic. As you said, actually, the latest Actually being with Dynap and Sumitomo Pharma, which was with an earlier business model called Design as a Service. We're always open to doing many kinds of deals structures, as you've seen, actually, I think our business development prowess over the past few years has actually shown that. Speaker 600:30:21But the way we see that AI is going to create real value is to think about what that product of the future looks like, what that sort of AI enabled drug starts look like. What we see as the hallmark on Exensio drug is a drug that uses advanced compute, Machine learning, AI and physics based methods to design precision design, the high quality molecule, but also venues in our deep learning multimodal approaches that Dave was talking Earlier to really define the patient selection strategy, bringing those 2 together in a model driven adaptive learning approach to learn about the drug. That's what we see. So it's 2 pieces of key IP, the molecule being designed by AI and using AI event to design the biomarker. Voice coming together is what we think is the hallmark of Exensio drug, and that's where we believe in the long term, the high value wealth can be created By effectively creating highly effective medicines with high response by actually designing the best molecule and targeting the right patients. Operator00:31:27The next question is from Vitram Pure Head with Morgan Stanley. Your line is open. Speaker 800:31:32Hi. Thanks for taking our question. This is Steve for Baikung. So I want to ask about the A2A program. Could you Discuss the prior treatment history for the patient you are enrolling into the trial? Speaker 800:31:43And when can we expect to see the initial data? And what's your expectation about The readout. Thank you. Speaker 600:31:51Thank you very much, Steve. For that question, actually, I want to hand the stage over to Mike Kramm, our Chief Quantitative Medicine Officer, who's actually leading our clinical development work here. Mike? Speaker 900:32:03Yes. Thank you very much for the question. So we have recruited our first patient into this program. It's a Phase onetwo study. And we use simulation guided clinical trial design to come up with an approach where we initially have a dose escalation, Aiming to make the correct decision at the earliest time point as to what the dose and treatment regimen is that we will take into a dose expansion phase. Speaker 900:32:29We're going to learn about the operating characteristics of the investigational compound. But at the same time, We are qualifying the adenosine burden score, as Andrew pointed out, as our tool to identify Which are the correct patients who might benefit from an A2A receptor antagonist in conjunction with a checkpoint inhibitor? As to when data will become available, this is a Phase III study in early development in oncology as many others. So it's really very similar to other programs and we are going to provide further guidance as time progresses. Operator00:33:19The next question is from Peter Lawson with Barclays. Your line is open. Peter Lawson with Barclays. Your line is open. Please go ahead. Operator00:33:35We will move on to the next question, which is from Chris Shibutani with Goldman Sachs. Your line is open. Speaker 1000:33:43Hi. It's Roger on for Chris. Just a quick question on 565, the MALT1 inhibitor. You're likely aware that J and J, they debut their Phase 1 data for their MULT1 inhibitor in NHL and CLL. I was just wondering if you'd comment a little bit on the inhibition of UGT1A1 and where do you expect 5 5 to come out in terms of differentiation, noting the competitive landscape. Speaker 1000:34:09Thanks. Speaker 600:34:11Thank you much, Roger. So Great question, actually. It's been a key point of how we have been designed a differentiated molecule. I'm actually going to hand this question over to Dave Hallett, our Chief Scientific Officer, To give you some more color on it. Speaker 1100:34:24Thank you, Anjou. And thank you for the question. I think the publication of the abstract, I think, is coming out Head of a European Oncology Symposium was very timely. So if you recollect the information that we put out Very recently around the design criteria around our MORT1 inhibitor and specifically the topic of Hyperbilirubinemia and driven by inhibition of UGT101. If you remember the takeaway story from those that We strongly believe that our molecule is differentiated from J and J and most likely quite a few other competitor molecules And that it has little to no activity at that particular transporter and is therefore likely unlikely to drive that particular side effect. Speaker 1100:35:14If you actually look into even into the abstract details, it's pretty apparent from J and J, as we would have predicted, that they do see hyperbiliary anemia in the clinic. They've had to take account of that in their recommended Phase 2 dose. I'm sure they would have preferred not to have done that. And So I think we stand by, I think that original assertion is that that was a really important differentiation criteria. I think it will our molecule, we believe, should be free of that particular Potential toxicity. Speaker 1100:35:47And more importantly, as I think as we highlighted is that, when asked to remember, it's very likely that a MOLT-one inhibitor will be used in combination with other agents like BTK inhibitors. And therefore, you need as clear as possible a safety profile so that you could dose that molecule as high as possible. So, no, it was I think it was I wish J and J well. I think obviously as they take that compound forward into patient studies, but I think it supported our notion about the differentiation angle of our own compound. Speaker 1000:36:20Thank Speaker 700:36:21you. The Operator00:36:23next question is from Peter Lawson with Barclays. Your line is open. Speaker 1200:36:28Hi, this is Shay on for Peter. Thanks so much for taking my question. Just wanted to touch base on the biologic side of your platform and maybe some progress And how you're thinking about balancing your biologics versus small molecule development and maybe even when we could see the first antibody program going into the clinic? Thanks so much. Speaker 600:36:44Excellent. Thank you very much. I'm going to hand over this question actually to Gary, who's in team has the algorithms for developing sort of biologics by design Speaker 700:36:58Gary? Yes. Thanks. And thanks for the question. And we mean, we're really excited about the way that we can introduce Biologics into our AI design platform and Professor Shailat, Dean has been working to build out the algorithms and all the technology to actually drive that forward. Speaker 700:37:16We're still at the point where we're developing a robust process and we're starting to run our 1st pilot project. So I think we're a little bit away from talking about a molecule in the clinic right now. But what I can tell you is we are developing actually, I'd say, world leading capabilities in the areas of Predicting structure and being able to do generative design into the antibody space. Speaker 600:37:42In terms of growing the pipeline, we certainly are now looking to think about how we might bring forward sort of our first programs going at and actually how then we start to map then of The antibodies, the capabilities we've been building actually to sort of our key of therapeutic areas sort of focus. One exciting thing is that we've already demonstrated Is that our precision medicine platform actually also works antibodies as well as small molecules. And that's a key thing then, because it allows us then to think about How then as we head towards the clinic, we could also bring to bear our precision medicine technology. And I think that's going to bring a unique differentiator as well actually in this particular Operator00:38:31The next question is from Steve with Morgan Stanley. Your line is open. Speaker 400:38:37Good morning, everyone. This is Gaspar on for Vikram. I have Speaker 900:38:41a question regarding your PKC program. So for the PKC data program in partnership with BMS, I was wondering how much visibility and control do you have Now into the path forward for this molecule and how it might progress through early stage development? Thank you. Speaker 1100:39:00So this is Dave Hallett. Thank you for that question. So in terms of public visibility, because BMS in license that particular program, they both now control the clinical development of that project, But also, obviously, kind of public disclosures that are related to that. As a trusted partner and partner of the GSE, we will receive kind of updates on that program ourselves. But just to reiterate to everyone who's on the call is that that particular asset It's begun a healthy human volunteer study in the United States in the early part of this year, and we look forward to kind of receiving updates from BMS as they progress. Operator00:39:50We have no further questions at this time. We'll turn it back to the presenters for any closing remarks. Speaker 600:39:56Thank you, Chris. As Exensia's CEO and Founder, I am proud to see our company maturing into an end to end precision medicines business spanning from discovery Into early development and supported at each stage by our innovative technology platforms. Our goal is to be as innovative in the clinic As we have been in discovery, our remarkable progress to date is a testament to the strength of the company. Thank you to everyone today on the call Thank you. Thank you. Speaker 600:40:31Operator, you may now disconnect. Operator00:40:35Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.Read morePowered by