Autolus Therapeutics plc

Q1 2023 Earnings Conference Call


spk09: Hello, ladies and gentlemen, and welcome to the Altalus Therapeutics First Quarter 2023 Financial Results Conference Call and Operational Progress. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising you that your hand is raised. To withdraw your questions, simply press star 11 again. As a reminder, today's conference is being recorded. I would now like to turn the conference over to your host, Alexandra Deschner, Investor Relations Consultant. Alexandra, please go ahead.
spk06: Thank you so much, Eric. Good morning or good afternoon, everyone. And thank you for joining us to take part in today's call for Autolis' first quarter 2023 financial results and operational highlights. I'm Alexandra Deschner, Investor Relations Consultant for AutoList. With me today are Dr. Christian Eisen, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. Before we begin, I would like to remind you that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and or regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements. For discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website. On slide three, you will see the agenda for today's call, which is as follows. Christian will provide an overview of our operational highlights for the first quarter of 2023. Lucy will then discuss the company's first quarter 2023 financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, we will, of course, welcome your questions. Over to you, Christian.
spk11: Thank you, Alexandra, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the first quarter in 2023. Moving to slide number four. We're really pleased with our program and operational progress during the first quarter of 2023, which is highlighted over the next four slides. We're making good progress with our pipeline of CAR-T programs, particularly with our lead product, Obicel, in relapsed refractory adult ALL patients. You will recall that we announced in December that the phase two pivotal clinical trial of Obicel in this patient population have met its primary endpoint. based on a pre-planned interim analysis of 50 patients with morphological disease, and that's verified by an independent data monitoring committee. This positive data triggered a $35 million milestone for our partner Blackstone Life Sciences earlier than anticipated. We're looking forward to presenting the top-line data of the FELIX study in an oral presentation at the American Society of Clinical Oncology Annual Meeting on June 2nd in Chicago. and a second oral presentation at the European Hematology Association Congress being held from the 8th to the 11th of June in Frankfurt. Updates on longer follow-up and additional sub-analyses of the data are planned for the American Society of Hematology meeting at the end of 2023, as well as at medical conferences in the first half of 2024. Operationally, the key goal for OBCEL is the filing for a biologics license application to the U.S. Food and Drug Administration by the end of this year. In February, Dr. Claire Rohde from UCL presented long-term follow-up data from our adult ALL patients in the OLCAR19 Phase 1 study of OBCEL at the tandem meetings of ASTCT and CIBMTR. The data demonstrated that 35% of adult patients remained in complete remission without additional anti-leukemia therapy at a median follow-up of 36 months, with ranges from 24 to 48 months. We're now looking at the broader range of development options for Obicel and Auto-122 beyond adult patients with acute lymphoblastic leukemia. In the Olkar extension study, we have reported Obicel's high level of clinical activity and well-manageable safety profile across non-Hodgkin's lymphoma indications and chronic lymphocytic leukemia. We're completing enrollment in this study and expect to report final data in a peer-reviewed publication. In the Curricel study, we evaluate OB cell in peripheral CNS lymphoma, and we have completed enrollment and continue to see consistent and encouraging safety and efficacy. With adequate follow-up, we are planning to publish the full data in a peer-reviewed journal as well. We're following with interest the early and very encouraging results from the team of Georg Schett and Andreas Mackensen at the University of Erlangen in Germany in patients with refractory systemic lupus and related B-cell-mediated autoimmune diseases treated with an academic CD19 CAR-T product. Considering OB cells' excellent activity and safety profile and combined with our commercial manufacturing base, this set of indications may become an attractive additional opportunity for the program. In an oral presentation at the 49th European Bow Marrow and Transplant Meeting in April, our key investigators, Dr. Sarah Goroshian and Persis Amrolia from Great Ormond Street Hospital in London, presented updated data from Auto 122, our CD19 and CD22 dual-targeting CAR-T product candidates. Kymriah ineligible pediatric ALL patients showed a high level of clinical activity and good tolerability with over 80% of patients achieving a molecular complete remission with no antigen-negative relapses seen with a median follow-up of 8.7 months. Included also were patients who had relapsed after chemariotherapy with CD19-negative disease. Additionally, data on the molecular design of Auto-122 and preclinical characterizations were published in molecular therapy in March and highlighted the state-of-the-art design of OTO-122 with its high sensitivity CD22 chimeric antigen receptor and the efficient core targeting leveraging OB cells CD19 chimeric antigen receptor. Turning to slide five and other pipeline updates. We're looking forward to updating the progress with the OTO-4 peripheral T cell lymphoma program in an oral presentation at the International Conference for Malignant Lymphoma in Lugano, Switzerland in June as well. Finally, we conclude, we continue to enroll patients into the McCarthy Phase I trial of Auto-8 in multiple myeloma and expect first data at the end of this year and expect to dose the first patient in the Phase I trial of Auto-6 NG in neuroblastoma this year as well. Turning now to slide number six, We've continued progress against our strategic and operational goals throughout the quarter. The company's new 70,000 square foot commercial manufacturing facility in Stevenage in the UK has continued to progress on track. Key equipment installation and validation were completed by Autolocin in the first quarter of 2023, enabling operational qualifications commencing now in the second quarter of 2023. This facility will have an initial capacity of up to 2,000 batteries per year sufficient to serve the global demand in adult ALL. Just 18 months from groundbreaking, we are now working on the qualification validation of the nucleus facility and remain on track for good manufacturing practice operations commencing in the second half of this year. We're also undertaking the development work and report generation for the CMC package planned to support a BLA submission to the FDA. Our industry-leading cell programming platform creates opportunities for collaboration and licensing. Through our relationships with BMS at Moderna, we added in Q1 a partnership with Cavaletta, granting them access to our proprietary RQR8 rituximab-induced safety switch, for incorporation into a set of selected cell therapy programs. In January, we also announced two changes to the board of directors. The company's non-executive chairman, John Johnson, who has held the role since September 21, will not stand for reelection at the ODLIS upcoming annual shareholder meeting. Additionally, at the end of February, Dr. Jay Brakstrom, who had served in ODLIS board of directors since August 2020, stepped down from the board after taking on a public CEO role at Scholar Rock. We also announced a change to our management team with Dr. Lucinda Crabtree, our CFO, also on the line today, stepping down or planning to step down in August 2023 to pursue a new opportunity. Searches for successes for these posts are underway. Finally, total cash and cash equivalents and restricted cash at the end of March were $343.4 million. We've had a diversified treasury approach in place, which served us well through well during the Silicon Valley Bank meltdown, and we continue to diligently monitor developments in the financial sector. Moving on to slide number seven, there are also several post-period events I'd like to bring to your attention. Last week, we announced that we had selected Cardinal Health as a core distributor for OVCell, giving us the platform and distribution capabilities required to commercialize a CAR T-cell therapy in the U.S. Cardinal Health's innovative depot model is intended to reduce delivery time by allowing for transit while product release is being finalized. Alongside this, we continue to build out Ottawa's own commercial infrastructure and are working towards onboarding the clinical centers over the course of this year. Also, last week, we held a virtual Capital Markets Day that presented the positioning and commercial opportunity for OB-Cell. The event started with Professor Laurie Muffley from Stanford University reviewing the disease, therapeutic options, and medical needs for adult patients with acute lymphoblastic leukemia. Professor Claire Rohde from UCL then introduced OB-Cell and the initial clinical experience in patients with ALL, followed by a video presentation of one of her patients and her experiences of living with ALL, with an ALL diagnosis, as well as her experience with the treatment regimen. With this deepened understanding of the physicians' and patients' view of this challenging disease, Dr. Matthew Gitlin talked about the ALL market and the perspective payers are taking. In particular, he looked at the cost of patient management and the impact on hospitals and payers, highlighting the substantial impact on cost of managing high-grade cytokine release syndromes and ICANNs. Finally, Chris Van Otelis is Chief Operating Officer Walk through the commercial roadmap for Obicel. We believe it was a very informative and well-attended event. And for anyone who missed it, a replay is on the event section of all of this website available to you. Finally, we recently announced the publication of two papers, the first of which included the publication of the preclinical data for auto 122 in molecular therapy, which I mentioned earlier. And the second, published in Molecular Therapy, Nucleic Acids, focused on a new set of cell programming modules based on novel FAS-TNF receptor kineras. This technology converts a threat to the CAR T cell into an activating or survival signal instead. We're borrowing here from a martial arts principle of taking an incoming blow and rolling with it. Slide eight, OV cell, moving to OV cell, with that, also moving forward to slide nine. OVCell has a unique mechanism of action. What's fundamentally different about our product candidate is that it has an ability to engage physiologically with the target cell, rapidly binding to the target, which delivers specificity, and paired with a fast off-rate for rapid disengagement from the target once the cell kill has been delivered. This unique engagement drives maximal activity while minimizing toxicity and is at the heart of the differentiated clinical profile we are observing for OB-cell in ALL and non-Hodgkin's lymphoma. Moving to slide 10. Our clinical experience with OB-cell in ALL shows a high overall response rate across all patient populations evaluated. In our prior All-Coron-19 study, we have 35% of patients in long-term remission at 36 months of median follow-up with a range of 24 to 48 months after receiving OB-cell and without receiving any further antileukemia therapy. The safety profile is well manageable with low levels of high-grade cytokine release syndrome and ICANs. The midsection of the slide shows the patients with long-term remissions have continued presence of CAR T cells over the entire observation period, pointing to CAR T cell persistence as an indicator for long-term outcomes. The program is developed under an RMAT, PRIME, and ILAP designation. Moving to slide 11. We've now completed the enrollment and dosing of our pivotal study, which we call the FELIX study, in adult patients with relapsed refractory ALL. As I mentioned, we announced in December that we had met the primary endpoint based on the overall response rate at an interim analysis on the first 50 patients followed for at least three months. Clinical benefits. in ALL will be assessed based on patients remaining in a sustained complete remission. We conducted this study in 34 centers, 24 centers in the US, seven centers in the UK, and three centers in Spain, enrolling patients from July 2021 to November 2022 during the peak infection period of the pandemic. It's important to realize that relapsed refractory adult ALL patients are highly immune suppressed the pandemic posed a significant added risk to them. Moreover, due to access restrictions and various other pandemic rules and regulations, we could actually not access our clinical trial sites for the most part of the FELIX study. This is about as difficult a population to work with as you can imagine, particularly in an environment where there is a high risk of infection, and indeed, we did lose a few patients to COVID. In many ways, This was more of a real-world study conducted under difficult circumstances. In addition to patient safety, every aspect of product delivery and logistics were pressure tested during the trial, with massively reduced air traffic and other impacts of the pandemic in our manufacturing teams. Remarkably, manufacturing for all patients from our facility in the UK turned out to be an asset also for US delivery, as the long-haul flights from the US to the UK have priority over domestic flights. We're pleased that we got it done under such challenging circumstances, and credits to our patients and their caregivers, clinical collaborators, and the whole ODELIS team for this achievement. As mentioned earlier, next key data is planned in oral presentations at ASCO and EHA in early June 2023. Moving to slide number 12. This slide summarizes the announcement we made in December regarding the pre-specified interim analyses of the first 50 out of 90 patients dosed that had reached at least three months of follow-up. The primary endpoint is based on overall remission rate, which includes patients in complete remission and patients in complete remission with incomplete bone marrow recovery, or CR and CRI. The ORR was 70 percent. All recent programs in ALL have used ORR as the primary endpoint in their respective studies. Safety analysis was conducted on a larger 92-patient data set and showed an excellent profile with high-grade cytokine release experienced in less than 3% of patients and high-grade ICANNs in less than 8%. ICANNs were fully reversible, and less than 25% of patients had any grade of neurotoxicity. In contrast, to prove T-cell or T-cell-engaging therapies, a very unusual profile in this patient population. And as I mentioned earlier, the data triggered a $35 million milestone from Blackstone. Moving to slide 13. This slide summarizes our current experience with OVCell across ALL. As you can see, the data are highly consistent across the various studies, both on safety and efficacy. Worth noting is that Carpal and Olkar were conducted prior to the pandemic, while both parts of the Felix study were conducted during the pandemic. Both the CAR-PAL and all CAR-19 studies were conducted in the UK, while the FELIX study was largely conducted in the US. What we did pick up is that the patients in the FELIX study were more advanced in their disease based on tumor burden and increased presence of so-called extramedullary disease. This is, in essence, again a function of leukemia that allows it to leave the bone marrow and successfully settle and grow in other organs. Patients with extramedullary disease respond poorly to antileukemia therapies. Moving to slide 14 to look at further into the data we presented at ASH from the old CAR-19 study. When we look into the outcome or long-term observation from the old CAR-19 study where we have up to four years of follow-up, you can see quite an unusual profile. We could see the clinical benefit in these patients is the ability to convert patients into complete remission, sustain them over time without additional therapy. And as you can see, obviously, a substantial proportion of the patients are indeed in sustained therapy. So if you go from bottom up, you can see at the bottom patients that obviously did not respond. We have then a group of patients that did respond but relapsed quickly, including patients that had lost a CD19 antigen. We have then a group of patients that actually relapsed with CD19-positive disease. Those are patients that have lost persistence of the CAR-T product. And then there is the top group with the long green survival lines where you can see patients that actually have continued remission. And in fact, those are also patients that have continued presence or persistence of CAR T cells. Overall, obviously, it gives us a lot of confidence in terms of the consistency of data, the data understanding the reasons when patients actually do relapse and what the causes for that relapse are. and obviously the proportion of patients that are in ongoing remission without any additional therapeutic need. Turning to slide 15, I thought it might help here to give you an overview of the ALL treatment landscape as it stands. The figure on the right represents the NCCN guidelines for the treatment of relapsed refractory ALL, and you can see it is sort of has two main arms. The lower arm actually looks at T-cell lymphoma which is a subset and relatively small group of patients. And the upper two arms actually include B-cell lymphoma, sorry, B-cell acute lymphoblastic leukemia. And with that, the disease setting that we're focusing on. We can also see that we see three novel therapeutics that are being incorporated into that scheme over the past 10 years. The first is Blenatumumab or Blencyto. This is a bispecific T-cell engaging anti-CD19 therapeutic antibody. It's given as a continuous intravenous infusion for 28 days at a cycle. These cycles can be repeated with two weeks of intervals in between the cycles. The patient starts at the hospital and eventually are discharged from the hospital with a container or a bag that actually contains the product that is continuously delivered through a central port. over the entirety of a treatment cycle. These bags are being changed typically once weekly and by a nurse that actually usually visits the patients at home to sort of support the therapy. These cycles can be repeated, but obviously the patient needs to be in a remission for a continued cycle or a next cycle to be received. The product is obviously very active. And it's particularly active in patients that have low disease burden. Now, unfortunately, like with all therapeutic options today available for adult patients with ALL, while the product is very active, it does not actually lead to long-term remissions. And that is one of the fundamental challenges that we have in the field is that we have active therapies, but we have a hard time converting those effects and responses into long-term remissions. The next therapeutic that we're looking at is inotuzumab or bisponza. This is an antibody-conjugated drug therapy. It is directed to CD22, which is expressed on most B cells that conform ALL. And this drug is also associated with a very high response rate, but also, like Blincyto, is not curative and, in fact, is usually used as a bridge to transplant. Finally, the newest product that is available is Brexacel or Tecardis, which is approved in 2021, which is the first CAR T-cell therapy approved for adult ALL patients. Both Blinsito and Tecardis, which are leveraging or utilizing T-cells, do show similar types of immunological toxicities, which are CRS and ICANS, whereas Besponza can cause liver toxicity. Overall, we do have, obviously, a view that if you have a product that has a high level of clinical activity with a well-manageable safety profile, obviously, it's very attractive for patients with the ALL. And if that product actually can translate into at least a proportion of the patients in long-term remission, I think that would represent a big step forward. Moving to slide 16 to look at the data from these programs in the space. Plencyto, as I mentioned, is a T-cell-engaging CD19-targeting monoclonal bispecific antibody that has become the standard of care in relapsed refractory ALL over the last few years. Key to its success have been the well-manageable safety profile. Key focus from a patient management perspective is the monitoring of ICANs, which impact about two-thirds of the patients. And in contrast, if you look at OB-cell, obviously substantially more patients do experience ICANNs. As I mentioned before, we've seen about 25% of the patients experiencing ICANNs with OB-cell. High-grade CRS for Blink-Syto is relatively low at around 5% level. And OB-cell seems to be similar, potentially slightly better in terms of the high-grade cytokine release syndrome level. Now, in contrast to BlinCyto, the CARTUS induces high-grade CRS in a substantially higher proportion of patients, in 26% of the patients, and high-grade neurotoxicity reaches about 35%, while 87% experience of patients experience neurotoxicity of any grade. Forty percent of patients receive vasopressors. This is a challenging safety profile to manage and often requires access to ICU. When we look at inutuzumab, while obviously active, the program has liver toxicity and is primarily used to bridge to transplant. None of the therapies established long-term remissions without subsequent stem cell transplant. Moving to slide 17. The market opportunity in ALL is unchanged, obviously as a consequence of the fact that we didn't actually see any significant move with regards to patients having long-term remissions. And so we still see, as we've seen about 10 years ago, 3,000 patients in high medical need for therapy between the U.S., Europe, and Japan. Moving to slide 18, when we look at the actual size of the market, we always look for good surrogates, and we believe that the sales of Blinzaiter are actually a good surrogate for our product. Firstly, in that Blinzaiter has obviously got a very similar mechanism of action, being CD19 T-cell engaging agents. Secondly, it's used largely in the same indication as a similar, albeit somewhat higher, CRS and ICANN level. So around 80% of the Blinzaito cells come from adult ALL, and around 20% of the cells from pediatric ALL. And very importantly, it's got a similar type of toxicity profile to OB cell as just reviewed above. The safety profile allows use of Blinzaito in a broad range of centers, not just in the academic transplant centers. And indeed, BlinkSight has had a record quarter in Q1, growing 41% year-over-year, with sales of 194 million reached in the first quarter. If we were to prudently assume quarterly sales remain constant and do not grow any further, we estimate that full-year sales could reach approximately 800 million, which corresponds to year-over-year growth of about 33%. This development highlights the meaningful commercial opportunity in adult ALL, which is driven by the well-manageable safety profile of Blincyto. Amgen reports a key driver for the increase is attributable to an expansion of the number of treatment centers where Blincyto is being used. We're also seeing that many CAR T centers are now also expanding their capacity for delivering CAR T cell therapy. So both Blincyto and ultimately Obicel have the potential to be used in a broader range of hospitals. Prices for CAR T therapy in the U.S. are in the range of $450,000 to about $500,000. Moving to slide 19. When we look at the steps forward, first of all, we're planning to disclose Felix data in an oral presentation at ASCO and also DHA. Long-term follow-up and additional sub-analysis are planned for ASH. We're targeting the BLA submission for the program towards the end of this year, MAA filing towards the end of the first quarter in 2024, and the U.K. filing in the second quarter of next year. That sets up very nicely for the key territories that we expect to be initially active in. In addition to the mature clinical data, the submission will also require data from the validation of our commercial manufacturing site. This work has been a key focus throughout the first half of 2023 and will do so into the third quarter. Importantly, our commercial manufacturing facility is set up to cover supply for approximately two-thirds of the estimated market from the start. We've talked about selecting Cardinal Health as our U.S. distribution partner, which is an important step. As we're moving through 2023, we need to prepare the key areas for commercialization. We're creating awareness for the program through a focused medical affairs program, and alongside this, we're establishing the value proposition for payers in our HTA dossiers, and finally, preparing for and starting center onboarding, a process that will take between nine to 15 months, to get each center ready to deliver CAR-T therapy. Slide 20. Moving to slide 21 to talk about the broader opportunity that we see with Obicel. As part of the old CAR extension study, we've been evaluating Obicel in relapsed refractory non-Hodgkin's lymphoma in CLL patients. We see consistently very high response rates combined with a very attractive safety profile suitable for outpatient use. That data will form the basis for the selection of the second indication after ALL. In terms of the life cycle, we're working on the next-generation version of OviCell with Auto-122. What we're looking to minimize CD19 antigen loss during relapses with this dual targeting approach. Building on OviCell, we are adding a highly potent CD22 CAR that can recognize very low amounts of CD22 on the surface of leukemia cells. This program was initially evaluated in children who had failed Kymriah or were not eligible for Kymriah therapy. In this very challenging population, we saw 83% molecular response rate, and this included also patients who had CD19-negative disease, demonstrating the efficacy of the CD22 CAR in isolation. Crucially, amongst the responding patients with a median follow-up of 8.7 months, where there have been no cases of leukemic relapse or emergence of MRD-related antigen escape. Together, these data indicate that combining our optimized CT22 CAR design with the CT19 CAR used in OV-Cell may be effective in preventing antigen loss-driven B-lapse in pediatric BALL. We're working on further streamlining the manufacturing process for Auto-122, knowing that we have an attractive lifecycle option. Timing of investment decisions in Auto-122 will be balanced with additional investments for OV-Cell. Switching gears and headed to slide 23. Our technology platform allows us to engineer a range of properties into T-cells that drive specificity of recognition, resilience against negative signals used by tumors to evade T-cell attack, and provide survival signals for T-cells. Our strength in T-cell engineering drives our pipeline and is also at the heart of the three collaborations that I've mentioned, which were reported on in 2022 and early 2023 with Moderna, BMS, and Cavaletta. On slide 24, we have a quick summary of the earlier stage programs in T cell lymphoma with auto 4-5, auto 6-NG in neuroblastoma, and auto 8 in multiple myeloma. Auto 4 and auto 8 are in phase 1 clinical studies, and auto 6-NG is expected to start during the course of the year. Moving to slide 25. T cell lymphoma is a very high medical need, similar to BALL. In fact, when you look at the NCCN guideline, it basically says that once you're through the frontline therapy and you relapse, you have to look for a clinical trial. Moving to slide 26. With its unique targeting approach, all of four starts to show meaningful clinical impact at the higher dose levels that we have explored. The first metabolic CRs are reaching one year post-treatment, and we continue to follow the patients. In addition, we have streamlined the manufacturing process and are exploring the activity in an additional cohort, and we're planning to report data at the ICML conference in June. Moving to slide 28 to talk about manufacturing. Cell manufacturing is obviously at the core of any autologous cell therapy. Developing a highly reliable, robust, and economical process is critical for the success of any program. In addition, we have to be able to deliver product at scale and matching capacity to the size of the medical need, which is important for a successful rollout of any therapy. Building on the robust and very well-characterized process used to manufacture for the Felix clinical study, we're standing up our commercial cell manufacturing facility called the Nucleus about a mile away from the clinical trial manufacturing site. This proximity is important as we will be able to move our entire staff to the facility, the new facility, and many, in fact, of our employees are already in the process of validating the Nucleus facility. Capacity of the Nucleus and its initial setup reaches 2,000 patient patches per year, or about two-thirds of the adult ALL market size. The Nucleus has been a fantastic project to realize with innovative design and about 75% off-site building to accelerate the building while maximizing the quality of the build. Moving to slide 29, which is the interest slide to the financial section, and with that, I would like to turn to slide 30, and pass the call over to Lucy for our Q1 2023 financial update. Lucy?
spk05: Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the first quarter ended March 31st, 2023. Cash and cash equivalents and restricted cash at March 31st, 2023 totals $343.4 million as compared to $382.8 million at December 31st, 2022. Net total operating expenses for the three months ended March 31st, 23 were $43.1 million, net of licensed revenue of $1.3 million, as compared to net total operating expenses of $41.8 million, net of grant income of $.2 million for the same period in 2022. Research and development expenses decreased by $2.7 million, to $31.3 million for the three months ended March 31st, 2023, from $34 million for the three months ended March 31st, 2022, primarily due to a decrease of $5.5 million in clinical trial and manufacturing costs, which is offset by an increase of $0.8 million in manufacturing material costs due to increased validation activities undertaken, primarily related to our ABCL clinical product candidates. A decrease of $0.2 million in depreciation and amortization related to property, plant and equipment and intangible assets due to the reduction in our depreciable asset base. A decrease of $0.1 million in legal fees and professional consulting fees in relation to our research and development activities. An increase of $1.4 million in salaries and other employment related costs, including share based compensation expense, which was primarily driven by an increase in the number of employees engaged in R&D activities. An increase of $0.7 million related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations. And finally, an increase of $0.2 million in facilities costs related to our new manufacturing facility, the Nucleus, in Stevenage, UK, as well as increases in costs related to maintaining our current leased properties. General and administrative expenses increased by $1.3 million to $9.3 million for the three months ended March 31st, 2023, from $8 million for the three months ended March 31st, 2022, primarily due to the following. An increase of $.7 million in salaries and other employment-related costs, including share-based compensation expenses, which was primarily driven by an increase in the number of employees engaged in G&A activities. An increase of $0.7 million in commercial readiness costs due to increased commercial readiness activities being undertaken. An increase of $0.1 million in general office supplies and expenses, facilities costs due to the increase in space utilised for G&A activities. A decrease of $0.2 million primarily related to a reduction in directors at offices' liability insurance premiums, legal and professional fees. For the three months ended March 31st, 2023, we recognised a loss on disposal of property and equipment of $3.8 million related to fixed assets no longer being utilised in the manufacturing facility exited in Stevenage, UK. There were no such disposals for the three months ended March 31st, 2022. Other income net decreased to $0.8 million from $0.9 million for the three months ended March 31st, 2023 and 2022 respectively. The decrease of $0.1 million is primarily due to the recognition of a lease termination loss arising from the termination and exit of one of our manufacturing suites in Stevenage, UK. Interest income increased to $3.4 million for the three months ended March 31st, 2023, as compared to $28,000 for the three months ended March 31st, 2022. The increase in interest income of $3.4 million primarily relates to the increase in interest rates on our interest-bearing bank accounts and short-term investments. during the three months ended March 31st 23 compared to the prior period. Interest expense increased to $4.9 million for the three months ended March 31st 23 as compared to $1.8 million for the three months ended March 31st 22. Interest expense is primarily related to the liability for future royalties and sales milestones net associated with our strategic collaboration agreement with Blackstone. Net loss attributable to ordinary shareholders was $39.8 million for the three months ended March 31st, 2023 compared to $37.1 million for the same period in 22. The basic and diluted net loss per ordinary share for the three months ended March 31st, 2023 totaled 23 cents compared to a basic and diluted net loss per ordinary share of 41 cents for the three months ended March 31st, 2022. Autoless estimates that its current cash and cash equivalents on hand and anticipated future milestone payment from Blackstone will extend the company's runway into 2025. With that, I'll hand it back to Christian to give you a brief outlook on expected milestones. Christian.
spk11: Thanks, Lucy. Moving to slide 32. To summarize, we think we have an exciting time ahead of us. Obviously, key focus on getting OBSEL into the regulatory process with the DLA filing targeted towards the end of the year. followed by filings in Europe in the first half of next year. Next up are planned Felix presentations, data presentations, ASCO DHA, and in addition we're preparing for commercial product supply and launch readiness. We also expect to provide updates on the pipeline programs with additional data and follow up during the year with our key programs that at this point are unpartnered and obviously create opportunity for setting up collaborations around them. Moving to slide 33, We got the cash-to-deliver, a very significant value step. We've got the data to show that with Obicel, we have a differentiated product profile that addresses a high medical need with limited competition and with possibly a transformational outcome. Alongside that, we have additional opportunities for Obicel in broader indications and a valuable pipeline for other oncology programs. As I mentioned, we're excited about our manufacturing facility. And we have a strong technology foundation validated by our collaborators, BMS, Moderna, Cavaletta, which recognize the value of our technology platform and allows us to monetize this value by way of option exercise fees, milestone payments, et cetera. Importantly, we look to do more deals also of this nature in the future. With that, I would like to thank you first for listening to our prepared remarks, and we're happy to take questions.
spk09: Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. All right, please stand by while we compile the Q&A roster. And our first question comes from Mara Goldstein with Mizuho. Mara, your line is open, please go ahead.
spk03: Great, thanks so much for taking the questions. So a couple things. One is, I'm just curious about the data disclosure on Felix at ASCO versus EHA, and will there be anything that's different or incremental at EHA? And then on the AutoAid program and data, expectation for data this year, can you speak to what the totality of that could look like? How many patients you might have data on?
spk11: Yeah, first of all, thanks a lot for joining, Mara, and thanks for the question. So the data that we're planning to release at ASCO DHA obviously are similar overall. What we're currently looking into is to look at the certain additional sub-analyses that we could actually include into the DHA presentation. Obviously, the data cut for the two presentations is obviously the same because they're literally a few days apart. But there's going to be probably slight differences in some of the sub-analyses that we'll be discussing. In terms of the further flow of data that we go, so in terms of the totality of the data, obviously we have involved a little bit more than 90 patients, which we'll be reporting on. And that gives us obviously a very good, I think, understanding of the overall profile of the product. And it gives us, I think, a good first look in terms of follow-up. And obviously by the end of the year, we'll be able to add an additional six months of follow-up, which will start to give us, I think, a pretty good sense of where the product is sort of trending to.
spk03: Okay. And then if I could just ask, since you included it in the sort of news flow on the pipeline that are collaborations, is anything specifically related to the current collaborators that you think might occur in this year, or is this a reference to potential new collaborations?
spk11: I think we'll keep that open. Both of those outcomes are possible.
spk03: Okay. Thank you.
spk11: Thanks, Marilyn.
spk01: Stand by for our next caller.
spk09: And our next question comes from Matthew Phipps with William Blair. Matthew, your line is open. Please go ahead.
spk07: Thanks for taking my call. So the autoimmune indications, obviously pretty interesting, and Novartis in Bristol talked those up pretty significantly last week during their own earnings calls, planning to move a kind of more rapid manufacturing process of their CAR-Ts into those indications. Do you think you'll take Ovisel as is right into the autoimmune? Would you look to maybe add any safety modules just in case of adverse events in that population? And just I'm wondering, do you have any thoughts on what the ideal durability of a CAR T is in an autoimmune disease? Is this something where you need consistent B cell exposure, or it's more of a reset of the B cell compartment?
spk11: Very good questions, Matt, and thanks for joining. Obviously, I think we all have been, you know, I think watching the team in Erlang very closely and had the opportunity to also review the data, obviously, much more closely as well. I think what we're seeing is quite an interesting profile in that the reset of the B-cell compartment obviously seems to be important in a number of ways. But what it basically would show or shows is that once the compartment is properly reset, that over time, although B-cells eventually come back, it doesn't look like the auto reactive B cells are coming back. So it appears to be actually a longer term effect. I would say the follow up is still limited, but it looks very encouraging in that regard that it could actually have been a proper reset of the compartment. The exact duration for how long you actually have to have B cell aplasia to achieve that goal, I think is very difficult to tell. What we do see is that in these patients that have overall a relatively normal They're not like ALL patients who have not gone through the same kind of rigor of therapeutic pressure. We do see actually that the persistence actually is not as long as in some of the products that were being evaluated to what was seen in ALL as an example or in other indications. So there's probably going to be a bit of a difference, but I think there is sort of a certain amount of period that you would like to see the B-cell aplasia to be in place to be sure that you really captured all these potentially autoreactive B-cells and be sure that you have a proper reset. But I think there's more to be learned in the space around that. And I think at this point, probably premature to sort of actually give you an exact number because I think it's just not known. In terms of design, we believe the design of the product actually is a really good design. It fits very well. and obviously with the safety profile that we now demonstrated in lots of different, you know, a number of different indications with very different challenging patients, I think sets us up very well in that setting. And then the final bit is obviously you have to be able to manufacture, manufacture efficiently, and also at the reasonable cost level, and it's obviously one of the key areas we've been focusing on for OB-GYN. We believe we're very well positioned.
spk07: Thanks, Christian. One quick follow-up. For the auto four update at ICML, will that include the full cohort of patients that were treated with the streamlined manufacturing process?
spk10: Probably not the full cohort as far as I can tell at this point, but it's going to be some additional updates, obviously a longer follow-up of the patients, as well as some translational data that I think will be helpful to understand kind of what the direction of travel is.
spk07: Great. Thanks for taking the questions. All right.
spk08: Thanks a lot, Matt.
spk09: Please stand by for our next question. And our next question comes from Yanan Xu from Wells Fargo Securities. Yanan, please go ahead. Your line is open.
spk12: Thanks for taking our questions. You mentioned that the FELIX study was enrolled during the pandemic and that presented some challenges such as patient loss to COVID-19. I was wondering whether conducting a study during the pandemic could have also affected the response rate or duration of response and other metrics of the study's endpoints. Along the same line of thinking, I was wondering whether the second half of the enrolled population was in any way less affected by the pandemic due to the timing of enrollment. And lastly, regardless of pandemic impact, I was wondering whether the second half of the enrolled patients have any differences in terms of their disease severity, such as the extramedullary involvement. compared with the first 50 patients in the interim analysis. Thank you for taking the questions.
spk11: Well, thanks a lot, Yanan. These are very insightful questions. And obviously, one of the things that, you know, we certainly were keenly observing, but also, you know, we're concerned about as we're going through the involvement of the study. Obviously, you've seen the data for the interim analysis. Obviously, we have a very high level of response rate. We have an excellent safety profile. So I think overall we do know that the program has done really well in this population and during this period of time. Now, one of the key things that we're in the process of evaluating, but we don't have the full answers at this point, is what are sort of the individual impact that we could see during that period of time attributable to the conditions that we were having, you know, restrictions on travel for patients which led to delays, for some of the patients to actually get access to treatment, et cetera. So a number of variables there, but as you pointed out, you know, this is not a constant, but it was, you know, a period where we had a lot of activity on the infection cycle in the first quarter of 2022, and then, you know, the differences if you look beforehand and if you look afterwards.
spk10: So we'll do a full analysis of that. We'll evaluate that in more detail, and I'm sure we're gonna be basically presenting that data
spk11: in more detail at one of the later conferences, most likely looking at ASH for kind of a full review of that. And so I think at this point it's premature, I think, to speculate on the questions you were asking. I think they're all very good questions and they're in fact questions that we're evaluating in the data and we're looking for various potential signs of impact, et cetera, over time. And we'll absolutely gonna share that with you. And once these analyses are completed, we also have to now follow up with all patients to understand the full impact that might have been there.
spk12: Understood. Thanks for taking the questions.
spk11: Thanks, Vinam.
spk09: Okay. Please stand by for our next question. And our next question comes from Gil Bloom. from Needham and Company. Gil, your line is open. Please go ahead.
spk04: Good morning, everyone, and thanks for taking our question. So just one for multiple myeloma here. It feels like the field is getting, the standards are getting higher and higher, and I have to admit there is evidence to show that dual targeting can be a good approach, but given the early stage of your program, where do you think you know, this treatment could fit, and what is the best strategy to move it forward, and maybe going allogeneic in some way? I'd love your insights here.
spk11: Yeah, very good question, Gil. Obviously, an interesting field, and I think a field we're all learning a lot about. Obviously, we have on the one hand, we have, you know, remarkable data coming out of the approved programs in early line therapy, and I think that is certainly one of the key areas where I think everyone can be really excited about and we hope that this obviously will have a big impact on patients. At the same time, we do see a massive gap between the demand for therapy and the interest for therapy and the actual ability to deliver the therapy. And that certainly has been sort of one of the biggest challenges that I think we've seen in the field. is that ability to deliver the market and to serve the market is at this point, you know, very far apart and quite disconnected. And that obviously, you know, on the one hand is a real challenge to manage because a lot of patients that would need access to therapy and do not have that access. But on the other hand, it also points to the fact that there is room for a certain number of additional programs to actually help serve the market and to really be able to sort of provide that remarkable type of condition and activity that we have seen to a larger patient pool. When we look in terms of the profiles, and I think some of the areas that you obviously would want to see, I think in this disease setting, you'd like to see a product that has a safety profile that can sort of be managed and handled in a broader range of centers, not just at the a smaller number of academic transplant centers, but be able to go more broadly than that. So I think safety is important also with the age sort of average of the population as well. And the other aspect, I think, is that we obviously haven't yet seen whether those initial remarkable activities do translate into true long-term outcomes. And I think that's an area that I think we will keep watching. And certainly, when we look at the ability to go after potentially driving cells, which is one of the reasons why we're including a CD19 component into AutoAid, but also having a more sustained presence of the product and persistence may actually be helpful to sort of actually create longer-term outcomes. That's what we're interested in understanding from our own product, from Auto8. And it's one of the key things we're evaluating in this initial phase one study. And I think depending on the outcome, I think there are sort of different paths that we can take from there forward. But I think it's somewhat premature in the absence of the data to sort of guide on a particular path.
spk04: Thank you, Christian. Very helpful. And just a quick one on Auto4. How is the company thinking about on this program, some interesting early data, but do you think this is more of a company-sponsored effort overall, or maybe more partnership material, or, you know, the jury's still out on that one? Thank you.
spk10: Yeah, good question. So, obviously, at this point, you know, we are very focused on delivering OB-Cell.
spk11: It's a full-out effort to deliver the program and really establish the kind of initial infrastructure for commercialization, both of manufacturing and and from an actual delivery perspective, commercial delivery perspective. And that certainly required us to sort of focus very substantially on OBSEL. And I think there's opportunity across the pipeline to consider entering into partnerships for some of the programs, also as a way to be able to actually move them more aggressively and more in parallel to the activities that we're conducting with OBSEL. So there's opportunity there. Obviously, we're excited about all the four. We think it's a very interesting program that starts to have very interesting data and certainly is a program that we feel has a real potential in a high medical need setting.
spk09: Thank you for taking our questions.
spk11: Thanks a lot, Bill. Appreciate it.
spk09: Stand by for our next question. Next, we have Kelly Shee with Jefferies. Kelly, your line is open. Please go ahead.
spk02: Thank you for taking my questions. For Auto 1, City 22, could you have to elaborate the definition of King Riot ineligible criteria? Do you see post-2019 car market attractive to pursue for Auto 1, City 22? And also, we saw two auto dual targeting programs targeting cities. 19-CD20 running trials in post-CD19 settings. Could you share your view between CD20 and CD22? Which one you feel is a better antigen to tackle CD19 relapse? Thank you.
spk11: Very good question. Thanks for joining, Kelly. So first one with regards to ODO-122 and the fact that we were describing these, the patients that we the two basic sort of settings that sort of exclude currently the patients certainly in the UK from chemo therapy. One is if you already have been on chemo and have failed, you're not eligible for a second round of chemo therapy. So that's one group of patients. And that includes also patients that actually have relapsed with CD19 negative disease that I did refer to before. The second part of the population is if you have isolated extramedullary disease, which also excludes you currently from chemotherapy.
spk10: And then there's, you know, certainly certain patients that are just too, in probably too poor condition to be considered and to be included on the commercial product. But it's a truly refractory population that we have treated here.
spk11: that we also would have expected if we had treated these patients with OB-cell, we might have been able to get about, you know, 40%, maybe if we're lucky, 50% into a CR, but certainly not anywhere close to the 83% that we have seen in this extension of the CARPAC study. Now, with regards to kind of the dual targeting approach and the choice of antigen, there was a number of considerations And we've seen programs actually for quite some time on the one hand targeting CD19 together with CD22 targeting or CD19 with CD20 targeting. We and others have been active in this space. Our focus has been on CD22. And the reason for adding CD22 was sort of twofold. First, similar to CD19, the expression of CD22 is actually seen in a wider range. of B-cell differentiation stages, particularly also present in very early stages that are driving acute lymphoblastic leukemia, and where in fact CD20 is absent. So you don't have CD20 expression on ALL as an example. The second consideration is that when we think about, you know, therapeutic pressure and selection against a particular target, Obviously, we do have the primary pressure when you think about non-Hodgkin's lymphoma indications to be on CD20 without the rituximab and the follow-on product from Roche as well, which both actually put heavy pressure. And what we're seeing is that patients that have been on prolonged CD20 therapy at time of relapse often have very low levels of CD20 expression or quote-unquote dim, if you look at it by fluorescent for lessons in a Pax order. So you sort of, through these therapies, sort of select for low levels of expression, which also then requires you to, if you want to go utilize that antigen as your second antigen in a dual targeting approach, that you really have to drive a product that has an ability to go into these very low levels of expression to ensure that you're not actually having or seeing escape due to that extended therapeutic pressure on the target. When we look at the data, I would say the early work that was done at the University of Wisconsin on CD19 and CD20 combination showed a good level of activity, but also eventually showed some relapses. There's limited data from some of the work that was conducted in China that showed also a good level of activity. And the longer-term outcome at this point, to our knowledge, is certainly not yet being published, but I'm sure we're going to see it at one of the upcoming conferences. Obviously, what's interesting when we think about CD19 loss, at least in our hands, we haven't seen that in the non-Hodgkin's lymphomas treated with OV-cells. So we haven't seen patients actually relapsing with CD19-negative disease. And we also actually have seen certainly an aggressive lymphoma. we haven't seen actually relapses of patients that achieve a CR, and most of the patients, as you may remember, did actually achieve an metabolic CR with Obesil. So whether or not there is a significant added contribution from CD20, I do not know at this point, and I think it's probably still, you know, something that we'll need to see over time. And, well, obviously, we're following the space. where we know the most about CD19-negative disease or loss of CD19, which is an ARL. Unfortunately, CD20 is not suitable. And the only other suitable antigen that you can go after that is actually useful in this setting is CD22, which is the reason why we chose it in the context of our life cycle for .
spk02: Very insightful. Thank you. Thank you.
spk09: Thank you very much.
spk01: And stand by for our next caller. And our next question comes from Astika Gunwerden at Truist.
spk09: Astika, your line is open. Please go ahead.
spk08: Hi, guys. Thanks for taking my question. So I just want to dig into the answer you gave to Gil's question for a minute, Christian. And maybe just ask, how do you compare the type and number of centers where you can get blimp-cyto versus the number of the centers where you can get tachycardia? And then as you plan to commercialize Obicel, what is your strategy for targeting these medical centers where it's likely to be used and the size of the sales force that you'll need? And then I have a couple of quick follow-ups.
spk11: Very good. Well, thanks for joining us, Rika. This is a very interesting question. And so when you look at where Insighto got launched, it got launched basically initially in the transplant centers. in the U.S. and also in Europe, which is in the U.S., give or take 60 centers that sort of really represent the real core of centers treating ALL patients with advanced disease. So you do have a pretty significant concentration of these very severely sick patients to be treated in this smaller number of centers. So I think that's the first aspect. And obviously we have In the current trial, in the Felix study, we got 24 of those 60 centers in the trial included and having gained experience with the product. When you think about the broader opportunity, that is really one of the key things that I think the learnings for Blincyton, and I think that will also be relevant for OVCell, is that the patients that have lower disease burden tend to be better manageable, tend to have less adverse events. And also in the case of Blenzyte, they also then have elevated levels of responses that were observed. And it is that profile that I think allows you to consider actually treating these patients in non-academic transplant centers in the US, which actually allows you to expand the footprint quite a bit and, frankly, allows you to get closer, on average, get closer to where the patients actually do live. And that actually takes risk out. It makes access easier. And I think it's certainly an important part. And what we do know with Blincyto is that if you look at the second course of treatment, the third course of treatment, actually those courses tend to actually induce very little adverse events. And they typically can actually be initiated without actually taking the patient into the hospital. So basically have an ambulatory setting, can be hooked up and then monitored for a short while, and then the patient can actually move on. So there is really the initial part where you have the major tumor burden that needs to be taken care of, where you have most of the adverse events, which is true also for the CAR T therapy, of course, the difference being We're only giving a single dose. We have to go, have not to go back. We don't have to change drug reservoirs, et cetera. So when we look at the actual adverse event profile then of the two programs of Blinzite and Obicel, you know, clearly Obicel, if anything, actually has an improved safety profile. And that actually gives you a very good, I think, proxy for the ability to deliver the product. Initially, we will also start, obviously, with the stem cell transplant centers. And, you know, the 60 centers or so that I quoted before, which is sort of the initial core, which address and allows you to actually reach a substantial proportion of, you know, 70% to 80% of the patients. And over time, as there is more experience with the product, as it was the case with Lincyto, we expect to be able to then actually increase the footprint to centers that are not academic transplant centers, obviously sophisticated and not academic transplant centers, and with that also expand the footprint, and with that should be able to reach the same patient population and have access and provide access to therapy for the same breadth of the patient population as we're seeing today with TENSYTO. So that is where we're looking at that, how we're projecting that. In terms of the Salesforce side, actually that's pretty focused. It's not a classical Salesforce either. Because what we're providing is more of a service than a classical marketing-driven commercial activity. And in fact, that's a very focused, given the number of centers, focused team. What we do see is actually that the size, although the workload is a bit different than with Flint-Side, is actually very comparable with a launch, basically size of your commercial organization for the US of about 120 to 150 people.
spk08: Great. Thank you, Christian. And then if I can follow up with a couple of quick ones. At ASCO, about what proportion of patients, of the 50 patients in the efficacy analysis, will have six months of follow-up? And then at EHA, I was just wondering if you could maybe give me a little color of what kind of sub-analyses will be presented. I might need a little help convincing my DOR as to why we need to go to Frankfurt.
spk11: there's always an opportunity to have a beer. And that seems like a good reason for why you might want to go. I won't fly to the COI. Okay, there you go. There you go. Okay. Look, when we went, so obviously we're going to report on all the 90 plus patients that were dosed in the study. When we look overall in the study, we will be close to somewhere between eight and nine months of follow-up on the median. So that gives you, I think, a pretty good sense of what that may look like. So that's what that, in terms of the overall data. The nature of what we're going to show ultimately on any additional potential analyses, I think that is still actually being finalized and would be too early to guide on. So I think it comes down to you probably have to go for the beer to be on the safe side. So you're there. You're not going to miss anything.
spk08: Okay. Appreciate the call, guys. Thank you so much. Thank you. Ah.
spk09: Okay, that concludes our Q&A for today. I would like to now turn it back to Dr. Christian Eiten, Chief Executive Officer, for closing remarks.
spk11: All right, well, thank you very much. First of all, thanks all for joining today. Fantastic to have you all on and to be taking the time. And we're obviously looking forward to hopefully seeing you in person during one of the two main conferences this summer, and if not, hopefully upon our upcoming trips to your respective areas. And with that, I'd like to conclude at this point. Thanks again, and looking forward to keeping you updated with the next update, obviously, at ASCO in a few weeks' time. Thank you.
spk09: And thank you very much for your participation. This does conclude our program. You may now disconnect.

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