Adaptimmune Therapeutics plc

Good day and thank you for standing by. Welcome to the Q3 2021 ADAPT Immune Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Julie Miller. Please go ahead.

Good morning, and welcome to Adaptimmune's conference call to discuss our third quarter 2021 financial results and business updates. Please review our forward-looking statements from this morning's press release as we anticipate making projections during this call. And actual results could differ materially due to several factors, including those outlined in our latest filings with the SEC. Adrian Rockliffe, our Chief Executive Officer, is with me for the prepared portion of this call. Other members of our management team will be available for Q&A. With that, I'll turn the call over to Adrian Rockliffe. Add.

Thanks, Julie. And thank you, everyone, for joining us. About this time last year, we laid out our 2252 strategy. We are now one year into that five-year strategy, and we've made substantial progress against each of the four pillars we set out then. The first pillar was that we wanted to have two marketed products targeting May J4, and the second pillar was to identify further indications for two additional BLAs for our Spear T-cell products. The first product we're targeting for approval is our first-generation TCR T-cell therapy targeting MAI-J4, Afamacel. In June, we presented initial data from the Spearhead 1 trial at ASCO, demonstrating that Afamacel is a life-changing therapy for people with synovial sarcoma and MR-CLS. We remain on track to file our first BLA next year for Afamacel, which we anticipate will be the first engineered T-cell therapy on the market for a solid tumor indication. Based on the data presented recently at ESMO from the SURPASS trial, we have shown that our next-gen MAJ4-targeted therapy, ADPA2N4CD8, is effective with responses in five different solid tumors, an overall response rate of 36%, and an 86% disease control rate. These data confirm the potential of a broader MAJ4 therapy franchise. In Q3, we announced that we initiated the Phase II Surpass II trial for people with esophageal and EGJ cancers. Today, we announced that we will start a second Phase II trial next year called Surpass III for patients with ovarian cancer. We continue to enroll patients in the original Phase I Surpass trial with a focus on rapidly identifying additional indications for late-stage development. Onto our third pillar, five new autologous products in the clinic from our extensive preclinical pipeline by 2025. We've reported substantial progress with additional HLAs, new targets, and next-gen programs, with our most advanced preclinical therapies being the next-generation engineered IL-7 TIL therapy in collaboration with CCIT Denmark, And our next-gen MAI-J4 targeted therapy incorporating IL-7 and CCL-19 developed in collaboration with Noil Immune. Additionally, the translational data we'll present at CTOS and CITC next week show the stellar quality of our translational science teams and how learnings from this research will help us develop better products to take into the clinic. Last but not least is our fourth pillar. to allogeneic products in the clinic by 2025. In this morning's press release, we confirmed that we plan to file our first IND in 2023 for a wholly owned allogeneic product targeting MAJ4. In Q3, we signed a fantastic strategic collaboration with Genentech that has now become effective and for which we will receive the upfront payment of $150 million in Q4. We also announced that we would open a dedicated allogeneic manufacturing facility next year. I believe that our allied platform represents a significant piece of the future of cell therapy for us and our partners, and this progress confirms we are amongst the leaders in the allogeneic T cell space. Looking forward, we will continue to deliver updates from our trials from a clinical and a translational perspective. Following the initial data presented at ASCO for our Pivotal Spearhead 1 trial, next week we will present a fuller data set at CTOS in an oral presentation delivered by Dr. Brian Van Tyne from Washington University. We will also present a poster highlighting translational scientific insights from this trial. At CITSE next week, we will present data demonstrating the positive impact of adding an AKT inhibitor to the expansion phase of our manufacturing process. It's a feature of developing cell therapies that epigenetic modifications during manufacturing have the potential to be as important as the genetic modifications we make to the cells themselves. In this same poster, we will present clinical translational learnings from patients in the SAFAST trial for whom we reported clinical data at ESMO, indicating that these manufacturing improvements, along with the next-gen enhancements, make an improved and more potent sphere T-cell product for people with cancer. These types of translational learnings are critical as we aim to bring forth further next-gen products and enhancements to better address solid tumors with our cell therapies. When looking across the pipeline of ongoing clinical trials with our 2252 goals in mind, we need to pursue our ambitions rapidly and efficiently and critically evaluate what is and is not a product. Today, we announced that we've ceased enrollment in our Spearhead 2 trial with Afamacel in combination with Pembrolizumab. Given compelling activity seen with our next-gen ADPHOM4CVA product across a range of solid tumors, next year we'll evaluate the combination of a checkpoint inhibitor with this therapy. We will not go into details today, but we'll update in due course about the best design and the path forward. We also announced that we have enrolled a sufficient number of patients in our Phase 1 trial with ADPA2-AFP for people with liver cancer, leading us to close screening. We presented data at ELCA demonstrating that ADPA2-AFP is an active product, with several patients receiving clinical benefits, including a durable complete response, and other patients with prolonged stable disease associated with a significant decrease in serum AFP. But the response rate to date is not what we had hoped for. We'll analyze data from the full patient population in this trial and determine next steps, including evaluation of alternative TCRs, manufacturing improvements, and potential next-gen enhancements. So far in 2021, we've delivered clear progress against our T252 strategy, and we will continue to deliver over the next four years. We're on track to file our first BLA. We're showing compelling data from Surpass, confirming the potential of the MAJ-A4 targeted franchise. And we're working quickly to pursue further late-stage trials, starting with the recently initiated Surpass 2 trial in esophageal and EGJ cancers and Surpass 3 in ovarian cancer, which we'll initiate in 2022. We're also planning to explore the use of checkpoint inhibitors alongside our NextGen product with the aim of identifying further treatment regimens for our cell therapies for people with cancer. Beyond our current clinical trials, we've continued to make progress with our autologous and allogeneic preclinical pipeline, including in collaboration with GSK, Estelas, and most recently Genentech. All of our progress this year brings us closer to achieving our vision of being a fully integrated cell therapy company. And you can really see this when you consider that we are filing a BLA and preparing for our first commercial product. while simultaneously building an allogeneic manufacturing facility for future generations of cell therapies for people with cancer. As we close out the year, I'm pleased with our progress and will provide further guidance for 2022 at the beginning of next year. With that, I'll turn it over for questions. Operator?