Orchard Therapeutics plc

Good day and welcome to the Orchard Therapeutics Q4 2021 earnings call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session and instructions will be given at that time. As a reminder, this call may be recorded. I would like to turn the call over to CEO and co-founder, Bobby Gaspar. You may begin.

Hello, and welcome to Orchard Therapeutics' fourth quarter and year-end 2021 financial results and corporate update webcast. I'm CEO and co-founder Bobby Gaspar. Before we get started, I want to remind everyone that this presentation contains forward-looking statements. Please refer to this slide and our latest SEC filings for more information. Three colleagues will be joining me on today's call. Braden Parker, our Chief Commercial Officer who many of you know from prior events, is here to discuss early launch execution with Lumaldi and our overall commercial strategy. Frank Thomas, President and Chief Operating Officer, is also with us, and I'm pleased to announce Frank has extended his transition through at least the end of the year to help oversee this next phase of our development and ensure Orchard is in the strongest possible position operationally and financially. This continuity will will be important as we progress our business and implement some of the changes to our portfolio that will be discussed today. Additionally, Fulvio Movilio, who recently joined the Orchard team as Chief Scientific Officer, will be available for Q&A following our prepared remarks. I've known Fulvio for many years, going back to his early career as a co-founder of the San Rafael Telethon Institute for Gene Therapy. He is a gene therapy pioneer, having made several contributions in the field and was most recently Senior Vice President of Translational Science at Odentos. As we'll outline during this webcast, our HSC gene therapy platform, including the research programs intended to treat larger indications, is a key component that will drive our growth and value creation strategy. So we felt now was the right time to introduce Forvio to the investment community. The business environment that we're operating in today has changed tremendously. as compared to just a few years ago. Within biotech, valuations have come down substantially, and the gene therapy space has been impacted even more dramatically, given factors such as the regulatory environment and commercial and reimbursement landscape. At Orchard, we are not standing still. We are responding to the current environment by ensuring our portfolio, our organization, and our strategy align to support our vision of bringing these incredibly valuable medicines to patients around the world. It is against this backdrop that we announced in this morning's press release our decision to strategically narrow the focus of our platform to synergistic indications where we believe HSC gene therapy is scientifically and clinically differentiated to deliver the most value. Importantly, the decision to narrow our portfolio and focus on the MALDI, our clinical stage MPS programs and key research programs is expected to extend our runway into 2024 and enable us to reach several critical value-creating milestones. For Ludmilde, this runway extension will give us more time to grow revenues in Europe and establish the appropriate commercial model. You'll hear from Braden later of some of the recent accomplishments that give us confidence that this is the right strategy. Also, we need to ensure our runway takes us well through the regulatory approval process in the US in 2023. An increased focus will allow us to continue to support and even increase our investment in diagnostics, newborn screening, and to expand into new markets in Europe and around the world. The runway extension also provides more time for our pipeline to mature and to continue to demonstrate why HSC gene therapy is the right modality for the programs we are advancing. For the research programs, the additional runway enables us to generate exciting data that could support the move into the clinic on our own or with partners. So we still have an ambitious set of programs, but with a more therapeutic focus that can provide leverage with manufacturing, distribution, and commercialization. We now have a deep body of evidence that demonstrates the potential durable effects of HSC gene therapy for the treatment of certain severe genetic diseases, including MLV and MPS disorders. Across our platform of current and former programs, we have generated data from more than 160 patients across seven diseases. All told, that is collectively more than 750 years of patient data that now stretches back to more than a decade of follow-up in the earliest treated clinical trial patients. The insights we gleaned from having one of the most extensive, if not the most extensive, data sets in the field of gene therapy are the foundation for our go-forward strategic focus and underpins our vision of ending the devastation caused by severe genetic diseases. By executing and delivering on a mission that has guided us from the start, we're confident we can create significant near-term value for our shareholders and the many other communities we serve. Now let's take a deeper dive into why we think our platform is best positioned to address certain rare neurometabolic conditions and why we're encouraged that we can ultimately translate the clinical outcomes observed to date into regulatory and commercial success. I'll now turn the call over to Braden to highlight our near-term neurometabolic milestones and the Maldives commercial progress.

Braden. Thanks, Bobby. Since Lameldi's approval and launch in Europe, we continue to build commercial momentum with positive engagement with health technology assessment bodies and payers throughout the region, as well as treating the first patients in a commercial setting. As Bobby and I will highlight in the next few slides, we are investing in the European launch of Lameldi to ensure we're identifying as many treatment-eligible patients as possible. And in the United States, we are working urgently to submit our BLA to the FDA in late 2022 or early 2023. Our experience with Lomeldy is what fuels our confidence in maturing our next wave of programs for neurodegenerative disorders. By the end of the year, we plan to initiate a pivotal trial for OTL203 and MTS1 Hurler syndrome and report data from the OTL201 proof of concept trial for MTS3A or Sanfilippo syndrome. These additional indications represent exciting commercial opportunities that can leverage much of the investment we are making in LaMeldie today. Since the launch, we've invested in priority activities and initiatives we believe will generate the most value for LaMeldie patients and providers. First, we activated five specialized treatment centers with relevant transplant and neurometabolic expertise in geographically important countries throughout Europe to administer LaMeldie. These same centers would be utilized to support future potential launches in similar indications. Second, on the access and reimbursement front, discussions with health technology assessment bodies and payers continues to progress well. In February, we announced a historic agreement with the National Health Service securing reimbursement for all eligible MLD children in England and Wales. In Germany, we received the highest possible therapeutic benefit rating in presymptomatic patients by the Federal Joint Commission. We're continuing to advance reimbursement discussions in the region, including Italy and France, and we are on track to secure an agreement in at least one additional market in the first half of the year. So we believe the progress in Europe and the value recognized by payers has differentiated this product and our team and demonstrated a willingness to ensure access for MLD patients across the continent. We hope to build on this success in additional European markets and eventually in other parts of the world. In order to help ensure we are identifying as many eligible patients as possible, support for early diagnosis through newborn screening continues to be an area of focus. We have four studies ongoing in Europe and one in the United States. These studies are intended to generate data to advance screening and diagnosis at birth and support the adoption of regular screening at the state, national, and regional levels as appropriate. These programs could also identify MLD patients to be treated commercially if reimbursement is in place at the time of diagnosis. While our near-term focus is on Europe and the United States, we're also assessing how to best expand our geographic footprint over time into other areas, including Latin America and Asia Pacific, in a way that's scalable, sustainable, and supports our long-term vision for value creation. Our partnerships with Genilac and GenPharm in Turkey and the Middle East, respectively, are examples of how we have expanded our geographic footprint in a capital-efficient manner. These partnerships are already bearing fruit as we previously announced the patient from the Middle East has been identified and referred for reimbursed international treatment abroad at OSR, our qualified treatment center in Milan, Italy. I'll hand it back to Bobby to discuss our U.S. regulatory plans and the rest of the portfolio.