Exscientia Plc

of Strategy and Investor Relations. Chin, you may begin.

Thank you, Operator, and welcome everyone to Accenture's first quarter 2024 financial results and business update conference call. A press release and 6K were issued this morning with our first quarter 2024 financial results and business update. These documents can be found on our website at investors.accenture.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. These may include statements about our projected growth, revenue, business models, preclinical and clinical progress and results, and business activities and performance, as well as our anticipated cash runway. Actual results may differ materially from those indicated by these statements. Unless required by law, Accenture 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 Dr. Dave Hallett, Interim Chief Executive Officer and Chief Scientific Officer, and Ben Taylor, Chief Financial Officer and Chief Strategy Officer. And with that, I will now turn the call over to Dave. Thank you, Chin.

While the first quarter of 2024 has been my first officially leading Accenture. The turn of the year marked the beginning of my fifth year as a senior executive at the company. With this experience and perspective in mind, I firmly believe that 2024 will be a year of opportunity for Accenture to continue making substantial progress on our mission to shift the curve of the pharmaceutical industry. The tangible benefits of our investment in platform and infrastructure are gaining pace. When we at Accenture refer to shifting the curve, we are referring to reducing the cost and timelines of contemporary drug discovery, design and development, while also increasing the probability of success. We have already demonstrated a repeated ability to lower the cost and time in the discovery phase of drug design projects. Our clinical pipeline has multiple shots on goal this year. to start to improve upon the low probability of success historically seen by the wider industry. These include our most advanced program, GTA-EXF617, or 617 for short, a potential best-in-class CDK7 inhibitor. We expect to present top-line clinical data from the dose escalation phase of the elucidate phase 1-2 study in the second half of this year. EXS4318 or 4318, a selective PKC theta inhibitor designed by Accenture and licensed by Bristol Myers Squibb for immunology and inflammation indications. 4318 has shown positive early results in its phase one study and has the potential to be a first in class immunology drug. And two compounds designed for sumitomo pharma, which are currently in psychiatric disease that could read out this year. All these candidates were created by Accenture because traditional methods have resulted in compounds with major developmental issues. Initial data from several programs will begin to demonstrate that our design solutions can significantly improve probability of success in the clinic. Today, we are providing updates for our highly differentiated LSD1 inhibitor, EXS74539, or 539, which continues its progression towards a phase one clinical trial in acute myeloid leukemia patients. And for the first time, announcing our plans for our MORT1 inhibitor, EXS73565, or 565, as a potential treatment for B-cell lymphomas, including chronic lymphocytic leukemia. We have built a platform with a focus on the efficient discovery, design and development of highly differentiated small molecule compounds. Our first of its kind automation lab integrating our AI design capabilities with automated design make test loops launched towards the middle of last year. We have already transitioned three programs over to the facility and will continue to add more during 2024. Prior to the opening of the lab, Every compound we have designed has been synthesized at a CRO or by our partners. We have analyzed synthesis data from these legacy campaigns and believe that at least 75% of these multi-step compounds and 90% of the overall reaction types are automatable and could have been run through our facility. This is important as we aim to push through the logistical and time bottlenecks of working with third parties and reduce the CRO costs associated with these activities. We are already starting to see an initial positive impact from the studio with like for like biology resource requirements coming down by at least 75% and in many cases by more than 90%. We develop and optimize assays directly on the platform rather than through an intermediate step. We have started to run unattended overnight assays, are executing multiple assays on the same plate and providing the teams with great opportunity to collect data. The active learning-driven nature of our entire approach from AI-driven design through automation and across the entire experimentation cycle means we can accelerate the discovery process even further than before and in a more cost-effective manner for Accenture. We are seeing operational efficiencies from the multi-year investments into our integrated platform. With these developments in mind, we are continuing to shape our business. around the automation of the design, make, test, learn loop, and ramping up activity through the automation lab. Our laser focus on this process creates the necessity to scale back or discontinue legacy activities that are not directly aligned with our core transformative purpose, automation, advancing our design platform, pipeline development, and partnerships. As part of this process, we intend to anchor our precision matching capabilities on those aspects that directly influence our pipeline or contribute to our discovery and translational activities. As a result of the sharpened operational emphasis, we expect to make a total reduction in headcount of somewhere between 20 and 25% of global staff, including reduced activities at our Vienna site. These changes will result in at least $40 million of annualized savings beginning in 2025. These changes are the natural progression for a technologically driven company and reflect our deep-rooted commitment to efficiency, not only with respect to what we do, but critically, how we execute and deliver it. Importantly, this step reaffirms our commitment to the key value drivers of our business, meaning our pipeline, our partnerships, and our drug design and automation capabilities. As I have already mentioned, we will share a few key updates across our pipeline as we look to build long-term value for our business, starting with 539, our LSD1 inhibitor. As a reminder, we believe that in 539, we have designed the first LSD1 inhibitor that uniquely combines a reversible mechanism of action with an appropriate half-life and CNS penetration. CNS penetration is an important property. because it has the potential to address brain metastases, which are prevalent in advanced disease. We believe that having a reversible mechanism of action is important because irreversibly deactivating LSD1 can contribute to poor control of platelet levels. Having a long half-life has the potential to have the same effect, and so the pharmacokinetic properties of the compound are also important. We have previously demonstrated in rodent studies that platelet levels are able to recover even with super efficacious doses of 539, whereas they remain depleted even for intermittently dosed irreversible LSD1 inhibitors. This unique combination of properties offers 539 best-in-class potential. The stoplight chart on this slide is color coded to show how close a profile compound is to an optimized target product profile. Green represents no deviation from the ideal property range, amber, a minor deviation, and red, a major deviation. The column on the right-hand side represents 539, which is green for all profile properties. The first two columns represent two LSD1 inhibitors developed by other companies. Both compounds have major deviations, both have long human half-lives, and neither are CNS penetrant. the Phase I-II compound also irreversibly deactivates the enzyme, compounding along half-life and presenting a challenge to managing platelet levels. What is interesting is that despite these deviations, the Phase I-II compound has been able to achieve proof of concept in an AML study, achieving complete responses in 33% of patients. On the face of it, this is a good result. However, it should be noted that to achieve this, Patients had to be dosed intermittently, and even then, high rates of grade 3 and 4 platelet count decreases were seen. We have previously shown data that demonstrates 539's preclinical efficacy is comparable to this compound. If this activity translates into the clinic, 539 has the potential to be just as efficacious, but with a better safety profile. With this in mind, we plan to submit an IMD to support a phase 1-2 trial in AML in the third quarter of this year, with the aim of opening the first clinical trial site across the end of 2024. We retain an interest in the development of 539 for solid tumors, including small cell lung cancer. By entering AML first, we are de-risking our program where clinical proof of concept has already been established. We believe we can leverage what we learn from this regulatory process for future opportunities for 539 and other indications. This Phase 1-2 trial will initially have a monotherapy dose escalation phase to help us identify the appropriate dose for testing, followed by a seamless Phase 2 dose expansion to assess safety and efficacy at that dose. Throughout this, we will continue to pursue our precision medicine approach to help support with biomarker selection and patient response prediction. In addition to 539, I'm also going to provide updates about 565, our MALT1 inhibitor. 565 has been precision designed to be highly selective, including over the enzyme UGT1A1. UGT1A1 mediates bilirubin glucuronidation, and inhibition contributes to hyperbilirubinemia. Hies' law is an assessment of high fatality risk from drug-induced liver injury that is based on elevated levels of liver enzymes and total bilirubin in the absence of other factors, for example, viral hepatitis or alcohol abuse. Many of the current standard of care treatment options that could be used in rational combination with a mortal inhibitor, such as BTK inhibitors, are known to cause drug-induced liver injury with concomitant elevations of liver enzymes. This would make combination with BTK inhibitors difficult in practice for those malt water inhibitors that do not share 565 selectivity profile. We previously shared data at ESMO late last year showing in vivo activity of 565 as a monotherapy and in combination. The combinations with ibrutinib demonstrated tumor growth regression in animal models. We have also recently generated compelling data in-house for combinations with next-generation BTK inhibitors, which we look forward to sharing at a medical meeting later this year. 565 is currently progressing through IND-enabling studies, and we plan to launch a clinical trial for patients with B-cell lymphomas, including chronic lymphocytic leukemia, in early 2025. It has been demonstrated from preclinical data that there are synergies between MOT1 inhibition and current standard of care treatment options. It has even been demonstrated that malt 1 combinations have the potential to overcome standard of care treatment resistant for some B-cell lymphomas. As you can see from the slide, there are approximately 22,000 B-cell lymphoma patients who fall into the second line of treatment each year. Our clinical development strategy will lay the groundwork for our ultimate goal of using 565 in combination with current standard of care treatment options. We will take the first step towards this by submitting either an IND or CTA application before the end of this year. I will now hand over to Ben to walk us through the business and financial updates.