Prelude Therapeutics Incorporated (PRLD) Earnings Call Transcript & Summary

Thank you for the invitation to present. I'm Jane Huang, President and Chief Medical Officer here at Prelude. We're really pleased to be with you today. Just to orient you, we have very deep research routes which has allowed us to develop a highly differentiated pipeline of products. Just the standard disclosures here on this next slide. And this is our slide about our portfolio and the history behind our company. For those of you in the audience who are new to Prelude, we are a clinical-stage precision oncology company solely focused to discovering and developing innovative small molecule medicines for patients with underserved cancers. Central to our core mission is our R&D engine that is run by a proven experienced team that has consistently delivered 1 Imd every 12 to 18 months since our inception, and I'm confident that we'll continue to do so in the future. Our pipeline consists of highly differentiated molecules that were designed and optimized to effectively block key oncogenic pathways in hematologic and solid malignancies to address very important unmet needs in patients with cancer. We see significant commercial potential for our clinical candidates, given the large addressable needs that we are pursuing in our development plans in our pipeline. On this slide, you can see our discovery and development approach, which is very distinct from a number of other early-stage precision oncology companies. And it's based on technology that is -- that are based on technology or target platforms. We have a balanced organization of discovery, preclinical and clinical development, led by proven and accomplished leaders from the -- on the executive team for each of the individual functions. And these teams work in a highly integrated fashion to drive the full range of R&D functions from target selection to finding our target candidate profile, biomarkers, translational and clinical development approaches for all of our programs. As you can see, what we think about is that we look at what targets might be interesting and important for those patients with highly unmet needs. We discover and target those targets through thinking through very carefully what is the best approach to go after them. So whether it be protein-protein interactions, or if they're degrader technologies, we optimize our approach to each of these targets. On this slide, you can see our portfolio of 4 different molecules that are currently in the clinic. This pipeline represents a highly differentiated and diverse set of novel molecules with profiles that were discovered internally to address specific needs of patients with cancer. And each of these molecules were optimized to possess very specific properties that make them unique. In the case of CDK9 on the left-hand side there, you can see that selectivity is a key differentiator, given the history of CDK9s and their experience in the past where adverse events made it difficult to further develop or combine. In the case of MCL1, MCL1 with prior companies have seen a lot of cardiotox programs that went on clinical hold. And our MCL1 inhibitor, we focused on a PK profile that allows for high target engagement for a short duration with -- in order to avoid the cardiotox. And for our next-generation CDK4/6, our emphasis is on selectivity, again, to have an improved adverse event profile, as well as high tissue and brain -- including the brain penetration to avoid, to be able to have a high therapeutic index, as well as to avoid any drug-drug interactions. And finally, SMARCA, which is the latest in the clinic. Selectivity over SMARCA4 is very important and paramount to elicit synthetic lethality. We chose a different therapeutic modality than others have, and we are a first-in-class and potentially best-in-class degrader. This should give you a sense of how we're approaching precision oncology in a very patient-focused manner. In terms of those molecules that are in the clinic that I just highlighted on the last slide, you can see the snapshot of our pipeline and what we've built over the last few years. These 4 programs that are in the clinic are differentiated in first or best-in-class. The data that we will be showing you in the coming year will demonstrate our proof of concept that the molecules are behaving as designed and -- for example, in the CDK9, we recently presented data at AACR that showed that we have very tolerable and safe drug in the patients that were treated in solid tumors. In terms of the MCL1 program, we have also an AACR presented data on the lack of cardiotox seen in 15 patients at the RP2D as well as the lack of cardiotox in the overall program in 26 patients treated in the solid tumor program. We are rapidly advancing this in the clinic for the heme side of things and as well as looking at monotherapy and combination therapy in MCL1. Moving on to the CDK4/6, this has also started in the clinic. We are in dose escalation. We are looking at a variety of different tumors to differentiate us in terms of looking at gliomas. We're looking at head and neck, endometrial cancers as well as HER2-positive/ER-positive breast cancer. This is, again, in Phase I dose escalation at this time, and we hope to show some data early next year around this. The latest in the clinic that we are very excited about is the very first-in-class SMARCA2 degrader. Just to describe this in a little bit more detail, some cancers exhibit SMARCA4 loss of function or SMARCA4 deletions. In order to initiate cell death, SMARCA2 is degraded with our SMARCA2 degrader. And having those 2 hits in these 2 different molecules will initiate the synthetic lethality. Additionally, in the clinic, we recently discussed at AACR that we are pursuing an oral formulations of not just as distinct entities from the IV of the SMARCA2 degrader, and these are forthcoming. Finally, we have additional programs in our discovery that because we have a very strong and robust discovery engine that are constantly looking for additional new targets, as well as areas of a high unmet need. As a result, in terms of what we have accomplished and what we are -- what you have to look forward for the coming year, we have, as I mentioned, presented for the CDK9 program our solid tumor data at AACR. And we have discussed our recommended Phase II dose in the solid tumor program. In terms of the heme side of things, this is progressing nicely, and we hope to update you regarding the recommended Phase II dose in heme in the second half of this year. And we are going to present initial clinical data on the heme side toward the latter half of this year. Secondly, our MCL1 program, again, we did present our 26-patient experience at AACR just a month ago, and we have also progressed our heme program. And we'll be approaching our RP2D in the second half of this year and updating our clinical data. Finally, we have the CDK4/6, again, presenting -- planning to present clinical data. It's in-dose escalation so the data will be preliminary. But we are hoping to show you that we have that differentiated safety profile because there are so many patients that do need better and safer CDK4/6s. And then finally, in the SMARCA program, we have initiated and are actively enrolling our SMARCA program, and we are going to be providing a clinical update in the second half of this year as well. So a very robust year for clinical data that will be coming out of Prelude and in terms of the milestones. And hopefully, in this very brief overview, I have been able to show you that we have a very deep clinical pipeline with a potentially best-in-class and first-in-class medicines, that we have multiple different data points that will be coming out in the next 12 to 24 months, and we will be driving these programs aggressively to these key inflection points. In terms of the emerging data, again, that was just presented at AACR. We have differentiated our safety profiles for the CDK9 and MCL1 programs, demonstrating the potential for class-leading opportunities. Our first-in-class SMARCA2 degrader will potentially be our best-in-class as well. It has significant lead over other competitors and offers a transformational potential for the company. And we have cash runway to the end of Q4 2024. So with that, I thank you for the opportunity to have introduced Prelude to you.