Arvinas, Inc.

Thank you for standing by. At this time, I'd like to welcome everyone to our Venus third quarter 2024 earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you'd like to redraw your question, again, press the star one. I will now turn the conference over to Jeff Ball. Please go ahead.

Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our third quarter of 2024 financial results and a corporate update, which can be accessed in the investor section of our website at our venice.com. Joining the call today are John Houston, our Venice Chief Executive Officer, President and Chairperson, Noah Berkowitz, Chief Medical Officer, and Andrew Sake, Chief Financial Officer. Angela Cacchetti, our Chief Scientific Officer, will join for the Q&A portion of the call. Before we begin, I want to remind you that today's discussion will contain forward-looking statements that involve risks, uncertainties, and assumptions. These factors are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which I urge you to read. Our actual results may differ materially from what is discussed on today's call. I'll now turn the call over to John Houston, our CEO, President, and Chairperson. John?

Thanks, Jeff. Good morning, everyone, and thank you for joining us for our inaugural earnings conference call. So, why are we starting earnings calls now, some six years after our IPO? Well, we have a truly exciting year ahead of us, and we are on the cusp of a huge transition for the company as we await our first pivotal data readout coming by the end of 2024 or the first quarter of 2025. In addition, we continue to make significant progress with a novel approach to discover, develop, and commercialize a new class of medicines for the treatment of cancers and neurodegenerative diseases. As we look now forward to providing updates each quarter as we move closer to our goal of becoming a multi-product commercial stage organization with a robust pipeline across several indications. We have a lot to discuss this morning, so I'd like to provide an overview of the topics we'll be covering. I'll begin with a brief overview of our VINUS, our ProTac discovery platform, and an update on our pipeline. Noah will then provide an overview of our expectations for the variant TAC2 trial and discuss our confidence in the combined ability of VEP-Degastrant or VEP-Deg with other metastatic breast cancer treatments. And finally, Andrew will provide an overview of our third quarter financial highlights. I'll add some closing remarks, including what we believe is the opportunity for VEDVEG, both as a combination and monotherapy, before opening the call for Q&A, when, as Jeff mentioned, we will be joined by our Chief Scientific Officer, Angela Kikasi. In the 11 years since our founding, we have taken major strides towards our mission to improve the lives of patients with serious diseases. Our pipeline of proteolysis targeting chimeras or protein degraders have been designed to harness the body's natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. This groundbreaking protein degradation platform has enabled us to create an exciting pipeline driving some of the most significant breakthroughs in targeted protein degradation in the industry. These breakthroughs include designing degraders with drug-like properties that are orally bioavailable and, when needed, able to cross the blood-brain barrier. Very soon, we'll have in hand the first-ever Phase III data readout for a ProTag. While the majority of our call this morning will be focused on our progress with VetDag, we will also briefly cover the advances we've made with our other clinical programs. In future calls, we will provide a deeper dive into our exciting pipeline that spans oncology and neuroscience. Our most advanced program, VetDeg, is an orally bioavailable protein degrader specifically designed to target and degrade the estrogen receptor for the treatment of patients with ER-positive, HER2-negative breast cancer. VETDEC works by degrading the estrogen receptor to block signaling through the ER pathway. By degrading the estrogen receptor, we believe VETDEC could potentially benefit patients with breast cancer who have ER-positive HER2-negative disease. As a reminder, in 2021, we entered a global 50-50 collaboration agreement with Pfizer to develop and commercialize VEDD-EGG as a potential next-generation ER-targeting backbone therapy of choice in breast cancer, as both monotherapy and in combination with other therapies. Together with Pfizer, we initiated the first-ever phase three trial with the PROTACT, the VERITACT2 trial. This is a randomized, open-label, multi-center trial of VET-DAG versus Fulvestrin in patients with ER-positive, HER2-negative advanced breast cancer whose disease progressed after prior endocrine-based treatment for advanced disease. The readout of data from this pivotal Phase III clinical trial will be a landmark event for Arvinas. We are on track to share top-line data by the end of 2024 or the first quarter of 2025 based on timing of events. If positive, these results will support our first new drug application and our potential transition to a commercial stage company. If proven effective, VETDIG can offer an oral monotherapy treatment in the second line setting, which could be a promising option for appropriate patients progressing on a CDK4-6 inhibitor-based regimen. For context, approved ER targeting treatments provide a few months of progression-free survival in this setting. a once-daily oral monotherapy that offers a clinically meaningful improvement in PFS and is well-tolerated, could be an important advance for patients and commercially very attractive in a highly fragmented second-line treatment landscape. Additionally, we continue evaluating VET-DEG in combination with other agents, including the approved CDK4-6 inhibitors, ribocyclib, and abemacyclib, in the ongoing Phase 1b2 TACTIV-U umbrella trial. We look forward to presenting initial Phase 1b data from the Abema Cyclob substudy of TACTIV-U in a poster at the San Antonio Breast Cancer Symposium later this year. The TACTIV-K trial, which is evaluating VetDeg in combination with Pfizer's PDK4-selective inhibitor, Atiramosaclib, continues to enroll patients. I will now turn to our earlier stage programs where we see exciting potential opportunities for PROTACs across oncology and neuroscience targets. First, neuroscience is an area where the unique properties of PROTAC degraders are particularly well suited, especially given the potential drawbacks of other drug modalities like antibodies and antisense oligonucleotides. Our most advanced neuroscience program, ARV102, is a novel oral prototype designed to cross the blood-brain barrier and target leucine-rich repeat kinase 2, or LARP2, which is a large multi-domain scaffolding kinase. We have shown that ARV102 achieves deep brain region penetration and degradation of LARP2 in non-human primates. We've also observed differentiation from inhibitors by showing improved effects on lysostomal dysfunction and movement of disease-relevant biomarkers in the central nervous system in preclinical studies. We intend to explore the potential of ARV102 in two severe neurodegenerative disorders that are linked to LRRK2 dysregulation. Progressive supernuclear palsy, a disease with a strong genetic link implicating LRRK2 with faster-progressing disease, and Parkinson's disease, where LRRK2 has been shown to contribute to the pathology of the disease. Earlier this year, we initiated dosing in a first-in-human phase one clinical trial of ARV102 in healthy volunteers. This ongoing Phase I trial is primarily designed to establish the safety of ARV102, but will also measure LRT2 degradation in the periphery and cerebrospinal fluid, or CSS, to establish the ability of ARV102 to cross the blood-brain barrier and degrade LRT2 in humans. The learnings from this Phase I trial will be valuable as we strive to address the incredibly high unmet needs in neurodegenerative diseases. We look forward to sharing initial data for ARV102 in 2025. We are also working with the Michael J. Fox Foundation's Parkinson's Progression Markers Initiative to identify novel LART2-dependent proteins that are altered in non-human primate CSF following administration of ARV102. We recently presented at the Michael J. Fox Foundation's annual Parkinson's Disease Therapeutics Conference where we disclose new preclinical biomarker data for ERV102. To our knowledge, this is the first data set to demonstrate that the degradation of LRRK2 in just these changes in pathway biomarkers of liposomal function and inflammation in the CSF of non-human primates, an exciting discovery suggesting that the PROTAC mechanism may lead to differential outcomes versus LRRK2 inhibitors. The presentation is posted in the scientific publication section of our website. Turning now to our third clinical program, we are also pleased with the preclinical profile of ARV393, a PROTAC designed to degrade B-cell lymphoma 6 protein, or BCL6, a transcriptional repressor and a major driver of B-cell lymphomas. The BCL6 protein facilitates B-cell tolerance of rapid proliferation and somatic gene recombination through the repression of cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response, which become dysregulated in several types of non-Hodgkin lymphomas. Protact-mediated degradation has the potential to overcome the traditional undruggable nature of BCL6. We are recruiting patients with non-Hodgkin lymphoma in a phase 1 clinical trial of ARV393 and look forward to updating you on our progress next year. Finally, we are preparing to file an investigational new drug application in 2025 for our KRAS G12D program. KRAS is a driver oncogene in several major tumor types and is associated with poor prognosis and resistance to standards of care. We are also developing a novel pan-K-RAS degrader and look forward to sharing more about this as we progress the promising program. With that, I'll turn the call over to Noah for a more detailed overview of the VETDEG program. Noah.