Cord Dorhrmann
Analyst · Morgan Stanley. Your line is now open
Thank you, Werner. And good morning and good afternoon to everybody on the call. Today, we would like to give you a little more background to the field of targeted protein degradation, Evotec’s approach to it and why we feel fortunate to have BMS as our partner here. Let's move to Page 16, for this. The field of targeted protein degradation is one of the hottest fields in the pharmaceutical industry as it harbors enormous potential. Small molecule therapeutics are the mainstays of the industry because they have proven to be highly effective. Furthermore, due to their all availability, they are particularly compelling when it comes to the ease of use. However, there are limits to traditional small molecules, in particular, the fact that many high potential drug targets lack proper small molecule binding sites to inhibit their function means that many high potential drug targets are essentially undruggable by our traditional small molecule approaches. The discovery that small molecules can also be used to specifically trigger the degradation, disease causing proteins very significantly expands the universe of drug targets that can be treated by a small molecules. This is the main reason why this field is drawing so much attention by the pharmaceutical industry. During the last two years, many pharma companies partnered with biotech companies to access technology or capabilities or know how to support their small molecule efforts in targeted protein degradation. At Evotec, we have been collaborating with BMS in the field of targeted protein degradation since 2018. Yesterday, we announced the extension and expansion of this collaboration into a long-term strategic partnership. And the cornerstones of this deal are summarized on Page 17. The aim of this partnership is to build an industry leading pipeline based on molecular glue degraders, which is expected to deliver multiple novel drugs into the market. The partnership between BMS and Evotec is a formidable match that BMS being an established pioneer and leader in targeted protein degradation, whereas Evotec will contribute industry-leading platforms including but not limited to, EVOpanOmics, and EVOpanHunter, but also a suite of AI machine learning tools supporting the whole drug discovery value chain. Evotec the receive $200 million dollars as an upfront payment and potential milestones in total of over $5 billion. In addition, Evotec is eligible to receive significant tiered royalties on each and every product developed through this partnership. Page 18, is putting this collaboration in context of other deals signed in the industry. Many pharma companies are not only interested in the field, but also signed sizable partnerships with biotech companies. One of the largest transactions was the acquisition of [Indiscernible]. Most of the other deals focused around small number of projects, or even just one project. When it comes to our partnership with BMS, we are excited about the opportunity to continue and expand our partnership to the leading company in the field. We believe that the scope, the length, and depth of the collaboration is unique in the industry and set Evotec take apart from all the other players. But let's take a step back and briefly talk about how a targeted protein degradation works, which is shown on Page 19. Targeted protein degradation works very differently from traditional small molecules, which usually functionally inhibit target proteins by binding to one of the active sites. In contrast, small molecule degraders also bind to the target proteins, but here the binding triggers proteolysis of the target protein and thus complete abrogation of the target protein as well as all its function. Triggering the degradation of the target protein is a multistep process as shown here. It involves a specific binding of a small molecule to a target protein, that the concurrent recruitment of an E3 ligase. The E3 ligase is then able to ubiquitinates the target protein, which subsequently goes through the proteasome. And this is where it's then ultimately degraded. Once again, proteolysis of the target protein not only abrogated function on a particular active site, but completely removed the protein with all its functions. Through this very different mechanism of action, molecular glue degraders have enormous potential in the field of small molecule therapeutics, which we briefly want to discuss on Page 20. As I already mentioned, small molecule therapeutics are the main thing of the industry, taking a drug orally is clearly the preferred way of administering a drug. Unfortunately, many potentially high the effective drug targets lacks suitable small molecule binding sites to inhibit their function effectively by a tradition of small molecule inhibitors. Small molecule degraders have demonstrated the ability to target even these historically undruggable target proteins. This is particularly important considering that about 90% of the human proteome cannot be targeted via traditional small molecules. So small molecule degraders are expected to significantly expand the universe of small molecule drug targets and thereby open up opportunities to develop novel breakthrough drugs and that orally available therapeutics. Besides being able to target drug targets that are historically seen undruggable small molecule degraders have also a number of other advantages over traditional small molecule inhibitors. Small molecule degraders work catalytically that means that once they have triggered the degradation process of a target molecule, they can do this again and again, and therefore require usually smaller doses and traditional small molecules. Furthermore, as they degrade the target protein, they are less likely to lead to the development of resistance. These advantages, and the tremendous potential of targeted protein degradation has obviously been recognized by the industry. On page 21, you can see that as of today, more than 150 protein degradation based therapeutics have been reported to be in discovery and development in the industry. Currently, the vast majority of these are being explored in the context of oncological indications but others are assured follow. What is interesting to note though, is that the focus is currently still on protect molecules rather than molecular glues. PROTAC which stands for proteolysis targeting chimeric molecules are fairly complex molecules, and are not very drugged like. They usually have two functional lens connected by a linker, which makes them bulky and unattractive from a number of factors. On the other hand, we have the molecular glues, which are much more elegant and drug-like molecules, and they have a number of advantages over PROTAC, which are summarized on the next page. In contrast to PROTAC’s molecular glues are more drug-like and also have better pharmacological properties. In addition, they're usually more synthetic -- synthetically tractable, and for this reason, are also more attractive from a cost of goods perspective. However, historically, PROTAC can be -- or more easily pursued via a rational drug design approach against almost any particular target. For molecular glues, rational drug design against a particular target has been more challenging because the structure activity relationships were less obvious for these kinds of molecules. However, combining BMS extensive experience and unique and extensive molecular glue library with Evotec’s high performance omics platforms, is the first unbiased and highly systematic approach to identify and develop a pipeline of medical glues, and as a great opportunity to develop a joint pipeline of molecular glue-based therapies. BMS is clearly the key pioneer and leader in the field of targeted protein degradation and in particular molecular glues as you can see on Page 23. They were the first to elucidate the mechanism of action of molecular glues. BMS has successfully built an exciting pipeline based on molecular glues. And of course, BMS generated over $15 billion dollars in sales based on drugs, which act is molecular glues already. Furthermore, over the last three years, they have assembled a unique industry leading library of molecular glues, which is genuinely refer to CELMODs, CELMOD stands for cerebellum E3 ligase modeling drugs. This is just another way of describing a molecular glue. Together with BMS, we created partnerships to explore if it was possible to systematically identify molecular glues using an omics-based approach and this is shown on Page 24. This collaboration, which initially was exploratory in nature, proved to be highly productive in identifying high potential molecular glues. This is the reason why we decided to extend and expand this collaboration into a long-term strategic partnership. As I already mentioned, Evotec will contribute a number of platforms but most importantly our panOmics and panHunter platforms which are uniquely suited for this purpose. On Page 25, we just want to give you a little bit of flavor on what sets EVOpanOmics phenomics platform apart from other maybe similar platforms in the industry. At Evotec we have built a unique proprietary omics generation platforms specifically for transcriptome and proteome data generation. These platforms, which are called screen, so I can screens PEP, are not only highly versatile when it comes to what cell and tissue types can be analyzed. But it even more importantly, these platforms operate at unprecedented scale and deliver unprecedented quality of data. I just want to mention a couple of metrics. Our transcriptomics platform operates at high throughput in 384 well format and still qualifies up to 15,000 genes per sample. This is a resolution that is usually only achieved via deep sequencing. Similarly, our proteomics platform is able to process tens of thousands of samples annually, quantifying up to 10,000 proteins based on single shot proteomics. So what makes Evotec’s platforms unique is really the overall performance. They are unique, highly industrialized platforms which operate at unprecedented scale, and deliver highest quality data in the most cost-efficient manner. As our platforms are delivering absolutely huge amounts of omics data, these data require a unique infrastructure for analysis, which is shown on Page 26. Exactly for this purpose, we have developed a platform that we call panHunter. PanHunter can manage and integrate huge amounts of omics data coming from patient samples, as well as a pharmacological data. The user-friendly integration of these datasets together with embedded AI machine learning data analysis tools allows data scientists to focus on answering key questions to drive their project forward rather than struggling to apply an AI machine learning algorithm to a particular set of data. This enables us to better select the most promising molecular glues, even very early in the process, we can better predict the efficacy and safety profiles of these compounds, and accelerate the transition from leads to candidates to INDs, as well as ultimately select the most appropriate patient populations for clinical development. We hope that this presentation has given you a little more insight into our strategic partnership with BMS in the field of targeted protein degradation. And in many ways the field of target protein degradation is still at its very beginning, there are clearly further opportunities in the space that go far beyond PROTACs and molecular glues, and even the proteasome driven targeted protein degradation. At Evotec, we continue to invest into these areas to create further partnership opportunities in the future. And with this, I'd like to thank you for your attention and hand you back to Werner.