Q4 2019 Earnings Call

March 3, 2020

Operator: Crabtree, Vice President, Investor Relations, please go ahead. Thank you, Kevin.

Lucinda Crabtree: Good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the fall of 2019. I am Lucinda Crabtree, Vice President of Investor Relations. With me today are Dr. Christian Itin, our Chairman and Chief Executive Officer, and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements, other than the statements of historical facts contained in this presentation, are forward-looking statements. Our actual results, performance, or achievements may be materially different from those expressed or implied by such forward-looking statements.

Lucinda Crabtree: For a discussion of the risks and uncertainties relating to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, please see the section titled Risk Factors in our Annual Report on Form 20-F filed on March 3rd, 2020, as well as discussions of potential risks, uncertainties, and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events, and the company does not assume any obligation to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation.

Lucinda Crabtree: On slide three, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the full year of 2019. Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. And, of course, we will welcome your questions following our remarks. So with that, I'd like to turn the call over to Christian.

Christian Martin Itin: Thank you. Thank you, Lucinda, and good morning to all of you, and thank you for joining us. I'm pleased to review our progress for the full year of 2019, as well as some recent company highlights from the fourth quarter. However, let me first begin by giving an overview of our corporate strategy on slide five. We're focused on progressing our potential best-in-class therapies, Auto I for Adult ALL, and Auto III for DLD-CL, with major value steps expected through 2020 and 2021. We are in the process of starting our first pivotal study with Auto I in Adult ALL, which will drive to completion in 2021 and target approval in 2022. We will also move our DLD-CL program, Auto III, to proof of concept by mid-year, and, assuming a GO decision at that time, would expect to be preparing for a pivotal study in this indication.

Christian Martin Itin: In addition to our new two lead clinical candidates, we will be delivering clinical milestones related to our T-cell lymphoma program, Auto IV, and also our first solid tumor indication. To date, we have seen encouraging initial anti-tumor activity from Auto VI targeting GD2, and we are now progressing an enhanced next-generation modular candidate, Auto VI-NG, into the clinic in the second half of this year. Auto VI-NG is specifically tailored to address some of the challenges related to the solid tumor microenvironment, as initially presented at CIDC last November. Additionally, we also see two of our next-generation development candidates enter phase one this year. It is Auto I-NG in pediatric ALL and Auto VIII in multiple myelomas.

Christian Martin Itin: Finally, I would like to highlight our longer-term value creation steps related to our broad and highly innovative next-generation preclinical pipeline. In addition, we've been working extensively to solidify our scalable, fully-enclosed manufacturing platform capabilities, which have to date delivered products to our Auto I and Auto III clinical programs. Turning to slide six, which gives an overview of our company highlights for fiscal year 2019.

Christian Martin Itin: As I mentioned, we have made great clinical progress with our elite programs, Auto I in Adult ALL and Auto III in DLBCL. In terms of our program in Adult ALL, we've presented updated results for all CAR-19, the phase one trial evaluating Auto I in adult patients with recurrent refractory ALL in an oral presentation at ASH. The trial enrolled patients with high tumor burdens who are considered high risk for experiencing the kind of toxicities normally associated with CAR-T therapy. As of the data cutoff of November 25, 16, 16 patients had received at least one dose of Auto-1. Auto-1 was well tolerated with no patients experiencing grade 3 or higher cytokine release syndrome and 3 of 16 patients, or 19%, who had experienced... Neurotoxicity, in particular patients with high levels of leukemia in the bone marrow. However, all of those neurotoxicities were spiritually resolved through steroids.

Christian Martin Itin: Of 15 patients available for efficacy, 13 achieved molecular remission at one month, and all patients had ongoing CAR-T cell persistence at the last follow-up. As touched on above, in the patients dosed with Auto-1 manufactured in a closed process, 9 out of 9 patients achieved molecular CR at one month and 6 months of end-free survival. Overall, survival in this cohort was 100%.

Christian Martin Itin: More recently, at the EHA-EBMT CAR-T meeting at the end of January, our Chief Scientific Officer, Dr. Martin Poulet, presented very encouraging updated data for Auto3 to treat adults with relapsed refractory diffused large B-cell lymphoma, which will expand on a later part of the presentation. At 50 in November, we presented exciting preclinical data for our Auto6NG program, which we'll talk about Finally, through the course of 2019 and early 2020, we completed two successful fundraising campaigns, raising in aggregate approximately $184 million in net proceeds.

Christian Martin Itin: In terms of our manufacturing capabilities, the Catapult site is now fully operational and delivering clinical products for patients in Europe and the U.S. We also continue to progress the build-out of our U.S. facility, which has an expected capacity of 5,000 patients per year. Moving to slide number 7, let's start the discussion with some more details about our most advanced program, Auto-One, in Adult DLL. We do believe there is a significant opportunity and unmet medical need in the relapsed and refractory B-cell acute lymphoblastic leukemia setting, which represents an underappreciated and significant commercial opportunity in terms of both the potential market size, as well as the high level of unmet need in the management of the disease. Worldwide, approximately 8,400 patients are diagnosed every year, with about 6,000 of those patients coming from the U.S.

Christian Martin Itin: While response to the initial combination chemotherapy regimen is encouraging, only 30% to 40% of adult ALL patients will achieve long-term remissions, and the median survival for adult patients with relapsed refractory ALL is less than one year. While Kymriah CD19-targeting CAR T-therapy was approved for pediatric ALL patients in 2017, no CAR T-therapy has been approved for adult ALL patients. The only redirected T-cell therapy approved for adult ALL is Blinatumumab or BlinCyto, a specific CD19 targeting T-cell engager. Blinatumumab has a 42% response rate, yet the durability of the response is limited, and its event-free survival is only 31% at six months. CAR-T therapies are clearly highly active in this setting, but we currently see no clear sense of durability without subsequent allografts. And it is worth noting that patients are generally more fragile with more comorbidities in this setting.

Christian Martin Itin: Initial CAR-T therapies, which have been notable for high incidences of severe CRS and cases of fatal neurotoxicity, show less than suitable profiles for addressing this pool of very sick patients. We will have further updates from our ongoing Phase I-OLCAR-19 study through the course of 2020 and starting at EHA, where we will have approximately six months of additional follow-up on the patients presented at ASH at the end of last year, and we will also include additional patients. Turning to slide number 8, I wanted to spend some time focusing now on how we have specifically designed ODA-1 for durable response without the need for allotransplant and achieved a reduced level of severe cytokine release syndrome. We wanted to achieve a product that can put pressure on the tumor for long periods of time and, at the same time, have a good safety profile.

Christian Martin Itin: We touched on this earlier, but this is particularly important as elderly patients tend to be. The durable benefit in adult ALL patients requires an ability to put long-term pressure on the leukemia. So when we look at the current generation of CAR T therapies in the field, they all share the same construction features, in particular, an identical binder called FMC63 to recognize the CD19 antigen on the leukemia cells. It is the binder that has the ability to hold on very tightly to CD19 and has a very high affinity. As a consequence, this creates a very unphysiological engagement with the target cell, the result being overly-activated CAR T cells, which drive cytokine release, differentiation, and exhaustion, all features that drive toxicity and lower persistence.

Christian Martin Itin: We hypothesized that for Auto-1, if we were able to generate a product that could deliver the kill but then disengage rapidly, we should be able to avoid over-activation of the CAR-T cell and the subsequent high levels of cytokine release and thus generate a program that has an improved toxicity profile and overall a better efficacy profile as well. We also believe that the product should be in better shape, less differentiated, and less exhausted, which should drive better persistence, and as such, should also be present over a longer period of time in the patient, exerting pressure on the leukemia. Turning to slide number nine, in this table, we compare the current standard of care, Blinitumumab or BlinCytome, to our program. Remember, most of the patients that we have treated have already received Blinitumumab or Inotuzumab and failed on those treatments.

Christian Martin Itin: As you can see, the CR rate for Blinitumumab is 42%. All patients in order one are at 87%. The event-free survival at six months for glenotumumab is 31%, with a reported 68% for the total population, as well as an improved number for the patients treated with the closed manufacturing process. This suggests a product profile that is emerging to be clearly differentiated from Glyncyta, most notably from other emerging CD19 CAR-T approaches. If these findings are confirmed in our registration trial, Ottawa has the potential to set a new standard of care in adult ALL. On slide 10, I'd like to summarize where we are with Auto-ON now in adult ALL. This program will be the first of those programs to move to the pivotal stage.

Christian Martin Itin: We filed a clinical trial authorization of CTA in the U.K. at the end of last year, and the IND is expected to be filed in the U.S. this month. The trial will be a single-arm study of approximately 100 patients in morphological relapse at sites in the U.S. and Europe. The primary endpoint will be overall complete response rate. Secondary endpoints will include MRD-negative complete response and event-free survival. We're targeting the second half of 2021 for a BLA filing.

Christian Martin Itin: Moving to slide 11, our program in diffused large B-cell lymphoma. We believe that DLB-TL is a large commercial opportunity given the market size and aggressive nature of this disease. LBCL is the most common type of Nohodgkin lymphoma, with approximately 25,000 patients diagnosed every year in the U.S. alone.

Christian Martin Itin: High-dose chemotherapy combined with a monoclonal antibody led to remission in about 50% to 60% of the patients. Thus, we expect the addressable population to be approximately 10,000 patients in the U.S. and EU5 combined. LDCL represents an aggressive and rapidly progressing cancer.

Christian Martin Itin: For patients who relapse or are refractory to first-line therapy, the current standard of care for second-line therapy consists of a platinum-based chemotherapy regimen with rituximab. Patients who respond to second-line therapy may go on to receive autologous hematopoietic stem cell transplantation, or HSCT. Patients who are not candidates for HSCT or those who do not respond to second-line therapy or relapse after HSCT are typically treated with third-line cell-rich chemotherapy.

Christian Martin Itin: These patients have poor prognosis, and treatment is generally palliative to try to prevent further cancer growth without intent to cure. There are two approved CAR T products available today, yet here there remains a high unmet need. Despite highly active CD90 CAR T therapies in the relapsed refractory setting, most of the responses are not durable, and toxicity limits broad application, particularly in the outpatient setting. Turning to slide number 12, we highlight the current state status of CAR T-cell therapies in DLBCL. Despite an objective response rate of 70% to 80% and high best TR rates of 40% to 55%, only 29% to 37% of the patients achieve a durable complete remission in DLBCL. Additionally, approximately a third of the CRs are lost over time, and loss of CRs is caused by PD-L1 upregulation, which contributes to CAR-T exhaustion and CD19 antigen loss. Safety is also an issue, with high rates of severe cytokine release syndrome of 13 to 22 percent and severe neurotoxicity of 12 to 28 percent. The early onset and severity of toxicities require intensive inpatient management.

Christian Martin Itin: Moving to slide 13, we profile the desired features of CAR-T necessary to target a broad use across all settings of care, including as outpatient therapy. Key features include high sustained complete response rates, preventing target negative relapse and checkpoint mediated resistance, as well as low severe CRS without intensive management and low neurotoxicity rates. The latter safety profile elements lend themselves to use that would not require intensive management of these patients and ultimately may allow you to actually treat these patients in an outpatient setting and avoid readmissions of those patients back at the hospital.

Christian Martin Itin: Continuing to slide 14, you can see that we have designed a product in Order 3 that targets a total addressable relapsed root factory DLBCO patient pool far exceeding those that can be reached by the approved products. Patients receive the approved products for the most part as inpatients in centers of excellence because of the high rate and severity of toxicities, and as such, the market opportunity is limited to approximately 20% of the patients that are treated in these centers and even smaller groupings of patients that are eligible for approved CAR T products. However, with minimal tox management of Order 3, this would allow treatment across all settings of care, increasing healthcare utilization of our product candidates and growing the addressable market and maximizing reimbursement options compared to approved products. We now move to slide 15.

Christian Martin Itin: We highlight the preliminary efficacy represented at EHA. As of the data cutoff of January 21, 2020, in the cohorts dosed at 450 million cells of order 3 plus pembrolizumab, five out of seven patients achieved a response, and four out of seven patients achieved a complete response. Turning to slide 16, we show that across all those levels, seven out of eight complete responders had ongoing complete responses at a median follow-up of up to six months, a range of one month to 18 months. All 7 out of 7 complete responders treated with ORTO3 and Pembrolizumab have ongoing complete responses as of January 21, 2020, at a median follow-up of 3 months, a range of 1 to 18 months. Looking at slide 17, ALDA-3 continues to demonstrate a safety profile much like the desired profile we described earlier, which may allow use in a larger outpatient setting. No patients experienced grade 3 or higher cytokine release syndrome were reported with primary treatment, and as of the data cutoff, no patient has experienced neurotoxicity of any grade in cohorts treated with ALDA-3 and pembrolizumab.

Christian Martin Itin: You will see this compares very favorably to other CAR T therapies both approved and in development across the competitive landscape. Overall, as summarized in slide 18, we are very pleased with the profile of Auto III to date. It is a successfully manufactured product for all patients from the cell and gene therapy catapult at Stevenage, and the Auto III program is on track for a decision in the middle of this year to advance the program to Phase II. From slide 19 onwards, I would like to conclude with a brief discussion of two other programs in our pipeline because they have the potential to bring additional value inflection in 2020 and beyond. On Slide 19, we highlight our unique targeting approach in T-cell lymphoma. We've been able to decipher very small differences in the amino acid sequence of the T-cell receptor beta chain, constant domain, such that we identify two mutually exclusive receptors which can be individually targeted by an antibody unique to the specific subtype.

Christian Martin Itin: Unlike B-cell approaches, an individual cannot live without T-cells, and therefore this approach allows us to salvage a subtype of T-cells likely to represent an equal proportion in the body in order to restore a functional immune system. Moving to slide 20, we recently revealed the clinical outcome of patient 1, who, despite having been treated at the lowest dose of 25 million CAR-T cells, showed a complete metabolic response. The patient subsequently had progression on day 71. Patient enrollment in our Phase I study with the more advanced product of a four-targeting TRBC1 is ongoing with supply from the catapult. As a result, we expect to present initial Phase I data by the end of 2020.

Christian Martin Itin: We draw our attention to our modular approach to enhance Auto6NG for the solid tumor microenvironment. We have empowered our next generation product to tackle the key areas that have previously been shown to hamper responses in the solid tumor environment. Auto6NG leverages the same TD2 targeting quality, but increased persistence, and also improves the persistence as well as helps the cells survive in a checkpoint-rich and TGF-beta-rich environment.

Christian Martin Itin: This product has been specifically designed to address persistence-controlled tumor defense. Turning to slide 23, at 50, we were excited to reveal data showing that the addition of these modules to the Auto6MG product was shown to augment its functions by extending T-cell persistence and rendering modified T-cells resistant to both TGS beta and PD-1, PD-L1-driven immune inhibition in vitro. They've also revealed that the clinical outcome of patient one in our Phase I program, despite being treated at a low dose, demonstrated encouraging evidence of activity. We believe Auto 6MG is positioned for additional value inflection as we commence the Phase 1 study in the second half of 2020. With that, I will turn over the call to Andrew for our third quarter 2019 financial update. Andrew.

Andrew Oakley: Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the full year, January through December of 2019. And we're on slide 25. Net total operating expenses for the 12-month period ending 31 December 2019 were $146 million, and that was net of grant income of $2.9 million.

Andrew Oakley: That compares to net operating expenses of $74.1 million, also net of grant income of $1.5 million for the same period. The increase in total net operating expenses was due, in general, to the increase in development activity to support the advancement of our product candidates, increased headcount, primarily in our development and manufacturing functions, as well as the cost of being a public company. Research and development expenses increased to $105.4 million for the year ending December 31, 2019 from $48.3 million for the year ending December 31, 2018. Cash costs, which exclude depreciation as well as share-based compensation, increased to $83.4 million from $41.5 million.

Andrew Oakley: The increase in research and development costs of $41.9 million consisted primarily of an increase in compensation-related costs of $20 million, primarily due to an increase in headcount to support the advancement of our product candidates in clinical development and investment in manufacturing facilities and equipment. An increase of $4.1 million in research and manufacturing consumables, in part due to the migration and expansion of our research and process development laboratories from Forest House to our new location in the MediaWorks facility. Preparations in advance of any potential disruption to supply arrangements that may occur due to Brexit, as well as validation and training costs as part of the start-up at the Catapult facility. An increase of $10.2 million in facility costs, primarily related to an increased number of facilities, mainly at MediaWorks and at Catapult.

Andrew Oakley: An increase of $3.8 million in project expenses related to activities to prepare, activate, and monitor clinical trial programs. And an increase in legal and professional fees of $0.5 million, consisting of a milestone payment to UCL Business PLC of $2 million in 2018 and a milestone payable to Naughty Mutant Biotech in the current year as well as an increase in IT and general office expenses as well. General and administrative expenses increased to $39.5 million for the year ended 31 December 2019 from $27.3 million for the year ended 31 December 2018. Cash costs in this area, which exclude depreciation as well as share-based compensation, increased to $26.6 million from $21.4 million. The increase of $5.2 million consisted primarily of an increase in compensation-related costs of $2.6 million due to an overall increase in headcount, an increase of $1.9 million in commercial activities, and an increase in public company compliance costs of around $1 million, an increase of $0.7 million in facility costs, and this was offset by a decrease of $1 million in IT charges and other office expenses.

Andrew Oakley: The net loss attributable to ordinary shareholders was $123.8 million for the 12-month period compared to $57.8 million for the same time frame in 2018. The basic and diluted net loss per ordinary share for the 12-month ended 31 December 2019 totaled $2.88 compared to a basic and diluted net loss per ordinary share of $1.48 for the 12 months ending 31 December 2018.

Andrew Oakley: Cash and cash equivalents at the end of the period totaled $210.6 million, and that compares with $217.5 million at the end of December 2018. Adjusting for the recent follow-on offering in January, where we raised gross proceeds of $80 million. Our cash at the end of January stood at around $286 million, and we anticipate that cash on hand provides us with a runway into 2022. With that, I will now hand the call back to Christian to give you a brief outlook on expected milestones. Christian

Christian Martin Itin: Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through 2020. Now, we move to slide 27.

Christian Martin Itin: The upcoming nine months will be an eventful period for us with multiple clinical milestones and opportunities for value creation. Our chief operational focus will be commencing the registration trial for Auto-1 in adult DLL in the UK and US. We also expect to report data across multiple programs and to progress a number of our other clinical trial candidates, specifically updates on our ongoing clinical trials, initiation of phase one study of Auto-1 in GMTiatric DLL in the first half of this year, a go-no-go decision on phase two initiation of Auto-3 in DLBCL in the middle of this year, initiation of a phase one study of Auto-6 NG in neuroblastom In conclusion, on slide 28, I'd like to recap the major messages from today's call. First, Auto I is our foundational program and the first Autolus program expected to move into the pivotal stage.

Christian Martin Itin: Given the positive safety and efficacy profile today, we believe that Auto I has the potential to be the best-in-class CD19 CAR-T in ALL. Secondly, our next priority is Auto III in DLBCL, which is obviously expected and slated for clinical data in the middle of the year. We expect to report full Phase I data for Auto III in the middle of 2020 to reach a decision point for phase II trial initiation thereafter. Looking ahead to the remainder of the year, we see opportunity for additional value steps for T-cell lymphoma, as well as the start of the Auto-6 Next Generation program targeting GD2-positive tumors. The company has a strong balance sheet with $286 million in cash, which will raise the run rate into 2022. And finally, we're looking forward to seeing many of you at the upcoming AACR, ASCO, and EHA meetings over the next few months, and are now happy to take questions. Operator, please open the line.

Operator: Ladies and gentlemen, if you have a question or a comment at this time, please press the star and then the 1 key on your touchtone telephone. If your question has been answered and you wish to remove yourself from the queue, please press the pound key. Our first question comes from Deb Chichette, by the way, with AC Wayne. Hi, good afternoon, Christian, and Andrew. Thanks for taking the questions. So I have a question on the barriers.

Christian Martin Itin: Oh, this is Aaron, Aaron from DevJet, by the way. I have a question on the barriers to outpatient treatment with autocartes and DLVCL. So we were looking at a study in which they treated patients with a median of only two prior lines with Lysosil in an outpatient setting, and they ended up hospitalizing 59% of the patients as a first sign of CRS or neurotoxin. So what do you think would be a reasonable level of hospitalization that could warrant expansion to the outpatient setting? And do you think that there could be more competition in certain subsets of patients in the outpatient setting for various autocrates? So a very good question, Aaron.

Christian Martin Itin: And it's obviously a very interesting kind of analysis when you look at the field, where you realize that at this point, only about 20% of the patients can be targeted with CAR-T therapy in the current settings, which are really focused on centers of excellence. And the reason for that is predominantly driven by the requirement for fairly intense management of these patients to deal with the adverse event profiles that the current products have. And what he basically quoted, that basically flux of patients back into the hospital that were considered initially to be treated in an outpatient setting, just indicates the need for a significant level of management of these patients to begin with. And that's a fundamental property of the product itself.

Christian Martin Itin: And I think it's shared by all of the current products that are either being approved or about to be approved. So, what I think we were highlighting in our presentation is that audit three at this point has shown no high-grade cytokine release syndrome, and this did not require actual management of the patient. So, we didn't actually have to put steroids in, or steroid covering, or we didn't have to put tocilizumab in these patients as a preventative measure, a management measure. This is the data, actually, from unmanaged patients. What was probably more surprising and obviously a remarkable outcome was the fact that we have seen no neurotoxicity of any grade in the patients that we have treated in combination with PEMBRA across the set And that is truly surprising because none of the programs targeting, redirecting T-cells, targeting CD19 to date have shown this type of a feature. All of them actually have neurotoxicity as a core type of adverse events that they do experience.

Christian Martin Itin: And the fact that we have seen none without managing the patients gives us a lot of confidence that we have a type of profile that should be well manageable also in an outpatient setting and also importantly, in centers that are not the few centers of excellence in the country but also much more broadly in the periphery where, in fact, most of the DLBCL patients do get treated in the U.S. And I think that's going to be a core Great, thank you. Thank you. Our next question comes from Chad Messer with Needham. That's great! Good day to all.

Christian Martin Itin: Thanks for taking my questions. Maybe we just start by continuing a little bit the discussion we were just having about Auto 3 and safety. We've got a go-no decision coming up. Is there an actual bar there you can describe?

Christian Martin Itin: I mean, 0% would be awesome, but maybe not all that practical to hold onto. I think if you had a low level of neurotox, low rate neurotox at a low level, I think that would be very well managed. We also should remember that the patients treated with Blinsite actually are treated in an outpatient setting, and they're managed that way. And the neurotoxicity rate, obviously, for Blinsite is not zero, but it is less intense than what we see with the CAR Ts that are currently going through approval or close to approval.

Christian Martin Itin: And so there's clearly a bar here that is not a zero number, but you definitely want to see a low level of neurotoxicity, and you want to avoid high-grade cytokine release syndrome, which really requires you to go back into the hospital. Okay, and then just again thinking about efficacy and safety bars for the Auto IV program. I mean, for T-cell lymphomas, we don't have a good standard of care to compare ourselves to, so what do we need to see later this year for Auto IV in order to get excited and optimistic about that one? I think what we would like to see is a good level of responses in those patients and evidence that we start to see also a reasonable level of persistence, so we get some durability of those responses. As you point out, this is a very devastating disease. There are very few options at this point.

Christian Martin Itin: And I think a program that gives you a reasonable level of remissions in these patients, together with some durability of response, will go a long way. And clearly, the bar for this indication is lower than what we're seeing in lymphoma and certainly much lower than what we're seeing in leukemia. All right, great. Well, thanks for looking forward to all the data you guys have coming up this year. Excellent. Thanks for joining us. Our next question comes from Byron in Minnesota.

Christian Martin Itin: Hi guys, thanks for taking my questions. Christian, on Auto II, can you just give us a status update on the NG program there? With multiple myeloma, they obviously went back and re-engineered a new program, which is called AutoAID, and that program is slated to get back into the clinic in the second half of this year. And then on Auto IV, thanks for the prior response, but if I look at some of the data with bendamustine, for example, in a relaxed refractory setting, I think there's some data out there that reports an OR close to 30%, CR of about 20%, 25%, and median DOR of about 3.3 months. Is that kind of like the bar that you would need to beat with Auto IV?

Christian Martin Itin: I think you want to be above that, but you're right, that is currently what the bar looks like in that disease setting. That is sort of the best we can do for these patients at this point. So you clearly want to be on the CRRA side, but it's clearly a very poor starting point. Okay. And then maybe just a question on Auto III.

Christian Martin Itin: How much data do we need to see later this year to move this program into Pivotal? You know, and I guess at what cell dose? Are you looking at, you know, greater than 150 million cell doses or are you looking at the 450 million cell dose to make a determination on the pivotal studies there? So we're clearly looking at this point at a greater than 150, we're treating at 450, and we'll have to see kind of how those levels do differentiate if they do much at this point. And we want to see a sustained CRA of 50% plus in this population.

Christian Martin Itin: 50% plus sustained meaning greater than six months, greater than three months, Great, thank you. Thank you. Our next question comes from Matt Phipps with William Blair. Hi, thanks for taking my questions, guys. So, two questions on auto one.

Christian Martin Itin: First, for the pivotal trial, how are you thinking about the criteria for baseline blast counts, and are you going to do split dosing based on blast counts in a pivotal trial there? Was there any difference in the kind of outcomes for that in the original all-car study? What do you think is most important there amongst all these different kinds of health economic endpoints that are being looked at? Right, so first of all, thanks for joining us, Matt.

Christian Martin Itin: With regard to the tumor load, the tumor burden of these patients, these are patients that are actually in relapse, in morphological relapse, which means that they have 5% or more blasts in the marrow. That's the first, I think, answer to your question. The second answer is with regard to the approach to dosing. We're going to use the same dosing that we have used for the All-Core 19 study, the Phase 1 study, which is that we look at a cutoff of 20% blasts. If the patient is above 20% blasts, we do a dose reduction, and we give a lower initial dose of the product to sort of manage the kinetics of the initial antitumor activity, which is really what determines to a significant part the overall toxicity profile in the patient.

Christian Martin Itin: So, yes, there's going to be a very identical approach that is used in the Phase 1 study. With regard to Auto-1 and kind of the parameters that drive, you know, reimbursement and so on, I think it's important, first of all, to understand that this is a patient group that is obviously very intensely managed to date. In other words, the treatment of adult ALL patients is very expensive. Even if the outcome is death, it is very expensive therapy because you have to manage these patients due to their immune suppression quite frequently at the hospital. Manage them through infections and so on and so forth, which often requires ICU stays for these patients. So managing these patients through their final year of life is extremely costly and is costing the system money.

Christian Martin Itin: So what we're doing with regard to collecting information, we're obviously collecting very diligently information related to resource utilization across all the patients in the trial, and we also do record the information from a patient's perspective with patient-reported outcomes as well. So we have both perspectives that we collect the data from, and that will also be built into the appropriate arguments for the respective payers. And as you know, depending on the healthcare system we're looking at, there are quite a few differences in what the various payer groups are actually looking for. Thanks, Christian.

Christian Martin Itin: One follow-up on the split dosing again. I know there were a couple of patients who had some neurotoxicity in the data presented today with Auto-1, and they had higher tumor burdens. Did those patients get the second half of the dose, or did the neurotoxicity occur with that first lower dose? It's typically linked to the initial expansion of the CAR T-cells, which is mostly driven by the first dose.

Christian Martin Itin: And what we obviously have seen, and that's what you're referring to, is that the patients that actually developed higher-grade neurotoxicity with Auto-1 in this particular indication were all patients with very high tumor burdens. We're looking at more than 50% tumor burden in these patients, and all of them actually responded well to a dose of steroids to get normalized. So obviously, what we can do with these patients is we can actually give these patients a steroid cover up front, given that we can identify the patients at risk here, and that should significantly reduce in a significant way the rate of high-grade neurotoxin in these patients. But there was a very clear population of the cells that were at risk of neurotoxin, and that was straight linked to very high tumor burden in the marrow.

Christian Martin Itin: Yeah, thank you. Okay, thanks Matt. Our next question comes from Greg Svanovic with Goldman Sachs. Hey, good morning, good afternoon. Thanks for taking my questions. I've got three this morning, if you don't mind.

Christian Martin Itin: My first question is, you've got a new program, which is an allogeneic approach. And so I'm just wondering, what's the thought process here? What's the target product profile you're hoping to achieve?

Christian Martin Itin: How's it different from other allogeneic approaches? So that's kind of all wrapped up in one question. My apologies for that.

Christian Martin Itin: My second question just has to do with the prime technology that you licensed last November; could you just give us some more color on that opportunity? And then my third question, if you could just provide some questions for Andrew just on 2020 OPEX and how we should think about trends relative to how you finish the year in 2019. Thank you. Okay. All right. I'm happy to get started on the first two questions.

Christian Martin Itin: So, the first question was related to the mention of approaches toward allogeneic approaches. Obviously, if you have patients that are underserved, either have basically no usable T cells that he can actually extract by leukophoresis, or are at such a speed of progression that he can't actually manufacture a product, that's obviously where you would like to have an alloproduct. That could go in there, even if that alloproduct would be inferior to the neural products that we're producing. And so, what we're looking at is using basically the technology approach that we've been using, which is programming cells and changing behavior at the protein level, which is the basic foundation in terms of the technology that we're using. We're creating protein modules that change the behavior of cells. What we have outlined is one module that actually changes the expression of the T cell receptor on the surface of the cells, prevents that from happening, and with that, obviously, you do prevent graft-versus-host disease.

Christian Martin Itin: We're doing some initial clinical testing starting towards the end of this year, in collaboration with one of our academic partners. So, that's sort of moving us, technologically, towards an allogeneic type of approach. So, that's what we're doing there. It builds on the same way of programming cells that we do, obviously, in general, and it avoids just the usual gene-editing type of approaches that we've seen typically across the space by actually making the modifications at the cellular level, at the protein level in the cell.

Christian Martin Itin: The second question was related to the prime technology that we've been licensed, and that is, in essence, a technology that looks to address heterogeneity within solid tumors, and there are different types of heterogeneity, one of which is related to the fact that often a tumor is not homogeneous for a single-target antigen. And in other words, you may have, if those of you who remember kind of the early HER2 stains when Herceptin came out, where you actually have, when you look at the slide stained with HER2 antibodies, you see actually kind of a very spotty staining, certain areas that are positive, many areas that are either just barely positive to actually straight negative. So in other words, there's heterogeneity in terms of target expression, and that's quite common. This is not the case for GD2, which is one of the reasons why we're working with that particular antigen.

Christian Martin Itin: But where you have heterogeneity, what you would like to do is you would like to actually take out the cells with the target antigen of choice that you can identify, but then also induce a natural immune response against the other parts of the tumor that are not positive, that are negative for the target antigen you can directly address with the CAR T cell. The prime technology actually allows you to boost that natural immune response against the tumor, and that's what we're using with these modules. And with that, I think I'm handing over to Andrew. Sure. Thanks for the question, Greg. Look, I'm not quite sure that we're really in a position where we're going to get sort of too granular in terms of OPEC's guidance for the year. You know, our guidance is that the cash runway we've got will last into 2022. You know, in a practical sort of sense, if we look at sort of three sort of buckets of cash spend in terms of R&D, G&A, and CapEx itself, you'll probably see an increase in all three categories during the course of 2020.

Andrew Oakley: But G&A, not too much. R&D, a reasonable sort of increase, but, you know, there were a lot of sort of costs in terms of the validation training and setting up of the catapult that in the 19-year that obviously won't occur in 20, but will then be sort of offset by in terms of actual patient processing or manufacturing. So I think that's about as far as we want to go from a guidance perspective in relation to OPEC's for 20. You know, we'll just stick with the concept that we've got a cash runway into 22.

Andrew Oakley: Okay, that's appreciated. Thank you very much. All right. Thanks, Greg. Thanks for joining us. Our next question comes from Jim Birkenau with Wells Fargo. Hello, good morning. It's Nick on for Jim's morning.

Christian Martin Itin: I really just want to focus on OrthoOne. Unfortunately, I joined the call a little late. I apologize if my questions will be answered from your prepared comments. But as far as the CTA goes, that was filed over three months ago. Have you enrolled a patient in the UK into the registration study? We're expecting enrollment starting this month in the UK. And then, as far as the U.S. goes, obviously, that's lagging in terms of the IND filing, but have you got sites identified ready to go? How many sites do you think you need for the trial? And is it feasible to warehouse patients? This is a test.

Christian Martin Itin: So, first of all, the U.S. IED is expected to be filed this month. That will allow us to actually enroll and treat the first US patients in the second quarter, which is what we have guided to and which we're on track for. In terms of the clinical centers, yes, they're absolutely identified. We expect to have approximately 30 patients in – sorry, 30. We expect the majority of those centers, more than 20 in the U.S., the remainder in the U.K. and rest of Europe. So, yes, all of those centers are obviously active, and we're in, you know, contracting processes, et cetera, as you would expect.

Christian Martin Itin: And so, in order to complete this study... Sorry, the last question is about warehousing patients. The answer is no, you can't.

Christian Martin Itin: This is a rapidly developing disease. The patients are in need of therapy, and you have to treat them. You can't just leave those patients with some intermediary type of therapy. It's very hard to do.

Christian Martin Itin: I mean, you may buy them within a two, three weeks' period sort of thing, but you can't actually park patients for much longer than that. And so Christian, your assumptions then for completing this trial, 1H21? Obviously, you have to have data on all 70, complete response rate data on all 70 patients, but what degree of follow-up are you going to need in order to, you know, declare the trial completed or for registration? So, the primary endpoint is CR8, and CR8 is determined typically after one month, so that is a very early time point in terms of the determination of whether you're tracking with the trial. It also will give you most of the safety at that point already; there are just very few safety events that happen after one month. And then you obviously want to see approximately six months of follow-up in these patients to get a good sense of what event-free survival looks like. So that is sort of the data point that we're looking at.

Christian Martin Itin: But as you enroll the patients, obviously, you'll have a range of follow-up for these patients, and we expect to discuss with the agency how we would actually file, what process we would file the particular trial. Right, right? Okay. And then will you allow bridging therapy in this trial? In general, and this is ALL, adult ALL, often in adult ALL, there can be some form of bridging therapy that is being used to manage the patient. But that is truly up to the treating physicians to determine what is appropriate to do with the patient. And there's obviously ranges of therapeutic options that can be used, typically some form of chemo. Unfortunately, obviously, with these patients, the chemo doesn't really allow you to actually get to any responses in this setting anymore, but it might allow you to sort of just buy, And just remind me Christian, for the U.S., will this product be manufactured in the U.S. or in the U.K.?

Christian Martin Itin: Any, Okay, great. Thank you very much. Okay, thanks, thank you much, appreciate it. And I'm not showing any further questions. All right, well, we'd like to thank you all for joining us this morning. Looking forward to, obviously, keeping you updated and seeing you on the road.

Operator: Thanks a lot. Have a great day. Ladies and gentlemen, this concludes today's presentation. You may now disconnect. Have a wonderful day.

He was in the Crabtree Vice President Investor Relations. Please go ahead.

Lucinda Crabtree: Crabtree, Vice President of Investor Relations, please go ahead. Thank you, Kevin. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the fall of 2019. I am Lucinda Crabtree, Vice President of Investor Relations.

Thank you Kevin Good morning, Good afternoon, everyone and thank you for taking Paulson stays code on the financial results an operational highlights for the full year 2019.

R&D Center Crabtree, Vice President Investor Relations with me today are Dr. Christian Archon, our chairman and Chief Executive Officer.

Lucinda Crabtree: With me today are Dr Christian Itin, our Chairman and Chief Executive Officer, and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements, other than the statements of historical facts contained in this presentation, are forward-looking statements. Our actual results, performance, or achievements may be materially different from those expressed or implied by such forward-looking statements.

Ugly, our chief Financial Officer.

Well, we begin I would like to remind you that during this call will be making forward looking statement.

All statements other than the statements of historical facts contained in this presentation of forward looking statement.

Our actual results performance or achievements, maybe materially different from those expressed or implied by the forward looking statement.

Lucinda Crabtree: For a discussion of the risks and uncertainties relating to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, please see the section titled Risk Factors in our annual report on Form 20F filed on March 3, 2020, as well as discussions of potential risks, uncertainties, and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events, and the company does not assume any obligation to update any forward-looking statements. You should therefore not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation.

For discussion at the risks and uncertainties relating to our business another important factor any of which could cause our actual results to differ from those contained in the forward looking statements. Please see the section talked with respect to sell annual reports on forms 20-F filed on March that Twentytwenty.

As well as discussions with potential risks uncertainties and other important factors in a other periodic filings with the FCC.

Forward looking statements contained in this presentation was that the company's views as of the data. This presentation regarding future events and the company has not seen any obligation to update any forward looking statements.

You should not rely on these forward looking statements as representing the company views as of any state subsequent to the data presentation.

Christian Martin Itin: On slide three, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the full year of 2019. Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. And, of course, we will welcome your questions following our remarks. So with that, I'd like to turn the call over to Christian.

On slide three you will see the agenda for today and it says well nice.

Christian will provide a brief introduction and that would be followed by operational highlights for the full year 2019, Andrew will next discussed the Companys financial result, and Christian will conclude with upcoming milestones and other competing common and of course, we will welcome. Your questions wondering how remarks, so with that I'd like to tend to cool over to Christian. Thank you.

Christian Martin Itin: Thank you. Thank you, Lucinda, and good morning to all of you, and thank you for joining us. I'm pleased to review our progress for the full year of 2019, as well as some recent company highlights from the fourth quarter. However, let me first begin by giving an overview of our corporate strategy on slide five. We're focused on progressing our potential best-in-class therapies, Auto I for adult ALL and Auto III for DLDCL, with major value steps expected through 2020 and 2021. We are in the process of starting our first pivotal study with Auto I in adult ALL, which will drive to completion in 2021 and target approval in 2022. We will also move our DLDCL program, Auto III, to proof of concept by mid-year, and assuming a go decision at that time, we'd expect to be preparing for a pivotal study in this indication.

Thank you for Doug Good morning told a view and thank you for joining us.

I used to review our progress for the full year of Plenti 19, as far as some recent company highlights into fourth quarter.

The first begin.

Giving an overview of our corporate strategy on slide five we're focused on progressing are potentially best in class therapies auto WAM for adult MLL older. Three four DLP show with major bodies, that's expected to be Twentytwenty on 2021, where the process is starting our first pivotal study with all of them. It's I'll tell you know which way.

Five to completion in Twentytwenty ball.

Target approval Twentytwenty too.

But also moved our you'll be still program or a three to proof of concept by mid year and assuming it goes decision at that time wed expect to be preparing for pivotal study into syndication.

Christian Martin Itin: In addition to our two lead clinical candidates, we will be delivering clinical milestones related to our T-cell lymphoma program, Auto4, and also our first solid tumor indication. To date, we have seen encouraging initial antitumor activity from Auto6, targeting GD2, and we are now progressing an enhanced next-generation modular candidate, Auto6NG, into the clinic in the second half of this year. Auto6NG is specifically tailored to address some of the challenges related to the solid tumor microenvironment, as initially presented at CITSE last November. Additionally, we also see two of our next-generation development candidates enter Phase 1 this year. It is Auto1NG in pediatric ALL and Auto8 in multiple myeloma.

In addition to our new to lead clinical candidates, we won't be delivering clinical milestones related to our T cell lymphoma program, although before and also our first of all the tumor education to date, we have seen encouraging initial anti tumor activity went from auto six targeting GT too and we're not progressing and enhanced next generation.

Sure look how did it always takes and Gi into the clinic at the second half of this year.

Oh, the six cents you specifically tailored to address some of the challenges related to the solid tumor microenvironment. As initially presented at 50 last November. Additionally, we also see two of our next generation development candidates into phase. One this year. It is all day long and Gi pediatric JLL and all the way in multiple myeloma.

Christian Martin Itin: Finally, I would like to highlight our longer-term value creation steps related to our broad and highly innovative next-generation preclinical pipeline. In addition, we've been working extensively to solidify our scalable, fully-enclosed manufacturing platform capabilities, which have to date delivered products to our Auto 1 and Auto 3 clinical programs. Turning to slide six, which gives an overview of our company highlights for fiscal year 2019.

Finally, I would like to highlight our longer term body creation steps related to our broad and highly innovative next generation preclinical pipeline.

In addition, we've been working extensively to solidify our scalable fully close manufacturing platform capability, which have to date delivered product to our auto on an older preclinical programs.

Turning to slide six which gives an overview of our company highlights for fiscal year 2019, as I mentioned, we have made great clinical progress with our lead programs Ottawa and it all parallel an older three anti obesity out in terms of our programming that all day and they'll be presented updated results for old Carbonite team to phase one trial evaluating all.

Christian Martin Itin: As I mentioned, we have made great clinical progress with our lead programs, Auto 1 in adult ALL and Auto 3 in DLBCL. In terms of our program in adult ALL, we presented updated results for All-Core 19, the Phase 1 trial evaluating Auto 1 in adult patients with recurrent refractory ALL in an oral presentation at ASH. The trial enrolled patients with high tumor burdens who are considered high risk for experiencing the kind of toxicities normally associated with CAR T therapy. As of the data cutoff of November 25, 16, 16 patients had received at least one dose of Auto-1. Auto-1 was well tolerated with no patients experiencing grade 3 or higher cytokine release syndrome, and 3 of 16 patients, or 19%, had experienced auto-1 and Neurotoxicity, in particular patients with high levels of leukemia in the bone marrow. All of those neurotoxicities were specially resolved with steroids.

The bottom in adult patients with recurrent refractory I know in an oral presentation attach the trial enrolled patients with high tumor burden Oh work are considered high risk for experiencing the kind of subsidies normally associated with car T therapy I.

So if the data caught off of November 25, 16 patients had received at least one dose of auto one.

The one was bell tolerated with no patients experiencing grade three or higher cytokine release syndrome and for your 16 patients or 19% <unk> had a experienced.

Toxicity.

Particularly patients with high levels of leukemia into bone marrow.

All of those neurotoxicity respectful result for steroids.

Christian Martin Itin: Of 15 patients available for efficacy, 13 achieved molecular remission at one month, and all patients had ongoing CAR T-cell persistence at the last follow-up. As touched on above, in the patients dosed with Auto-1 manufactured in a closed process, 9 out of 9 patients achieved molecular CR at one month and 6 months of entry survival. Overall, survival in this cohort was 100%.

Oh 50 patients Evaluable for efficacy 13, chief molecular remission.

At one month and all patients had ongoing car T cell persistence at the last follow up.

I've touched on the block in the patients dosed with Autobahn manufactured in a close process nine out of nine patients achieved a molecular a CR add one month and six months event free survival overall survival in this quarter was 100%.

Christian Martin Itin: More recently, at the EHA-EBMT CAR-T meeting at the end of January, our Chief Scientific Officer, Dr. Martin Poulet, presented very encouraging updated data for ORO3 to treat adults with relapsed refractory diffuse large B-cell lymphoma, which will expand on a later part of the presentation. On 15 November, we presented exciting preclinical data in our Auto6NG program, which we'll talk about Finally, through the course of 2019 and early 2020, we completed two successful fundraising campaigns, raising in aggregate approximately $184 million in net proceeds.

More recently at the H.A.M.T. car T meeting end of January our Chief Scientific Officer, Dr., Mark and play presented very encouraging updated data for over three to treat adults with relapsed refractory diffuse large b cell lymphoma.

Which will have which will expand on later part of the presentation.

I'd say, it's in November we presented exciting preclinical data are all the six and GE program, which well talk to a little later finally through the course of 2019 at early Twentytwenty be completed two successful fundraisings raising accurate aggregate approximately $184 million in net proceeds.

Christian Martin Itin: In terms of our manufacturing capabilities, the Catapult site is now fully operational and delivering clinical products for patients in Europe and the US. We also continue to progress the build out of our US facility, which has an expected capacity of 5,000 patients per year. Moving to slide number seven, let's start the discussion with some more detail about our most advanced program, Auto-One, in adult ALL. We do believe there is a significant opportunity and unmet medical need in the relapsed and refractory B-cell acute lymphoblastic leukemia setting, which represents an underappreciated and significant commercial opportunity in terms of both the potential market size as well as the high level of unmet need in the management Worldwide, approximately 8,400 patients are diagnosed every year, with about 6,000 of those patients coming from the U.S. and the top five European countries.

In terms of out of manufacturing capabilities to kind of pull side is not fully operational and delivering clinical products for patients in Europe and the U.S.

We also continue to progress to build out of how you guys facility, which as expected capacity for 5000 patients per year.

Moving to slide number seven let's start with discussion with some more detail of our most advanced programs Autobahn at all day, along though.

We do believe Theres, a significant opportunity an unmet medical need into relapsed and refractory b cell acute lymphoblastic leukemia, setting, which represents an underappreciated and significant commercial opportunity in terms of both the potential market size as well that's the high level of unmet need in the management of the disease.

Worldwide approximately 8400 patients are diagnosed every year with about 6000 took those patients coming from the U.S. and the top five European countries. While response to initial combination chemotherapy regimen is encouraging only 30%, 40% if at all day L. patients will achieve long term revisions and the median survival for adult pace.

And with relapse refractory CLL is less than one year.

Welcome, Brian Cdnineteen targeting car T therapy was approved for pediatric and adult patients in 2017, no car T therapy has been approved for it all together patients.

The only redirected T cell therapy approved for adult MLL, it's better to them admirably inside so are you guys specific cdnineteen targeting T cell engager, but not to AMAP has a 42% response rate yet the durability of the response is limited and this event free survival is only 31% at six months.

Christian Martin Itin: Blinitumumab has a 42% response rate, yet the durability of the response is limited, and its event-free survival is only 31% at 6 months. CAR-T therapies are clearly highly active in this setting, but we currently see no clear sense of durability without subsequent allograft, and it is worth noting that patients are generally more fragile with more comorbidities in this setting. Initial CAR-T therapies, which have been notable for high incidences of severe CRS and cases of fatal neurotoxicity, show less than suitable profiles for addressing this pool of very sick patients.

Car T therapy are clearly highly active in this setting, but we currently see no clear sense of durability without subsequent allograft and it is worth noting that patients are generally more frac child with more comorbidities into setting.

Initial car T therapies, which have been notable with high incidence is a city of Crs and cases, a fatal neurotoxicity show less than suitable profiles for addressing this pool very sick patients.

Christian Martin Itin: We will have further updates from our ongoing Phase 1 OLCAR19 study through the course of 2020 and starting at EHA, where we'll have approximately six months of additional follow-up on the patients presented at ASH at the end of last year, and we will also include additional patients. Turning to slide number eight, I wanted to spend some time focusing now on how we have specifically designed Odo1 for durable response without the need for allotransplant and achieved a reduced level of severe cytokine release syndrome. We wanted to achieve a product that can put pressure on the tumor for long periods of time and, at the same time, achieve a good safety profile.

We will have further updates from our ongoing phase bond Olkaria, 19th studies through the course of Twentytwenty I'm, starting a D.A.J., where we will have approximately six months additional follow up on the patients presented at ash at the end of last year and we also will include additional patients.

Turning to slide number eight I wanted to spend some time focusing now on how we have specifically designed older ones for durable response without the need for allo transplant and achieving a reduced level of severe cytokine release syndrome, we wanted to chief of product. The can put pressure on the tumor for long periods of time at the same time, except to get a good safety.

Profile.

Christian Martin Itin: We touched on this earlier, but this is particularly important as elderly patients tend to be a lot more fragile, have more comorbidities, and are much more likely to tolerate or much less likely to tolerate toxicity. Durable benefit in adult ALL patients requires an ability to put long-term pressure on the leukemia. So when we look at the current generation of CAR-T therapies in the field, they all share the same construction features, in particular an identical binder called FMC63 to recognize the CD19 antigen on the leukemia cells. It is the binder that has the ability to hold on very tightly to CD19 and has a very high affinity.

We touched on this earlier, but this is particularly important elderly patients tend to be a lot more fragile more comorbidities on a much more likely to tolerate are much more or less likely to tolerate toxicity.

The durable benefit in adult MLL patients requires an ability to put long term pressure on leukemia. So when we look at the current generation of Karkhi therapies in the field. They all share. The same construction features in particularly an identical binder cold and FMC 60 freight to recognize the cdnineteen averaging over leukemia cells. It is the baidu.

That has an ability to hold on very tightly to cdnineteen and has a very high affinity as a consequence. This creates a very physiological engagement with a target. So the results being overly activated car T cells, which drive cytokine release differentiation and exhaustion all features that drive toxicity and lover per se.

Christian Martin Itin: As a consequence, this creates a very unphysiological engagement with the target cell, the result being overly activated CAR-T cells which drive cytokine release, differentiation, and exhaustion, all features that drive toxicity and lower persistent risk. We hypothesized that for Auto-One, if we were able to generate a product that could deliver the kill but then disengage rapidly, we should be able to avoid overactivation of the CAR T-cell and the subsequent high levels of cytokine release and thus generate a program that has an improved toxicity profile and overall a better efficacy profile as well. We also believe that the product should be in better shape, less differentiated, and less exhausted, which should drive better persistence, and as such, should also be present over a longer period of time in the patient, exerting pressure on the leukemia.

That's.

Hypothesize that for Autobahn that if we were able to generate a product that could deliver the killed, but then disengage rapidly we should be able to avoid over activation of the car T cells and the subsequent high levels of cytokine release, and Dallas generate a program that has an improved toxicity profile and overall a better efficacy.

File as well, we also believe that products would be in better shape, let's differentiated less exhausted, which should drive better positions kinda starch should also be present over a longer period of time inpatient exerting pressure on Virginia.

Christian Martin Itin: Turning to slide number 9, in this table, we compare the current standard of care, Blinitumumab or Blinsidot to our program. Remember, most of the patients that we have treated have already received Blinitumumab or Inutuzumab and failed on those therapies. As you can see, the CR rate for Blinitumumab is 42%. All patients in order 1 are at 87%. The event-free survival at six months for Blinitumab is 31%. We've reported 68% for the total population, as well as an improved number for the patients treated with the closed manufacturing process. This suggests a product profile that is emerging to be clearly differentiated from BlinCyte, most notably from other emerging CD19 CAR-T approaches.

Turning to slide number nine and this table, we compare the current standard of care Blinatumomab, Brooklyn side, though to outer profile remember most of the patients that we've treated have already received during the two AMAP or in the tusa, Matt and failed on those therapies as you can see the CR rate for Atlanta, too and that is 42% all patients in older.

Our at 87%.

That free survival at six months for Atlanta to map is 31% reported 68% for the full for the total population as well as a and improved a number for the patients treated with be close manufacturing process.

This suggested product profile that is emerging to be clearly differentiated from glenside, most notably from other emerging Cdnineteen car T approaches.

Christian Martin Itin: If these findings are confirmed in our registration trial, Ottawan has the potential to set a new standard of care in adult ALL. On slide 10, I'd like to summarize where we are with Auto-One now in adult ALL. This program will be the first of those programs to move to the pivotal stage.

If these projects are confirmed that registration trial Autohome has the potential to set a new standard of care in adult MLL.

On slide 10, I'd like to summarize where we are with Autobahn now and it all together though.

This program will be the first of all those programs to move to pivotal stage, we have filed a clinical trial authorization or CJ into UK at the end of last year and the idea is expected to be filed with the U.S. This month.

Christian Martin Itin: We filed a clinical trial authorization of CTA in the UK at the end of last year, and the I&D is expected to be filed in the U.S. this month. The trial will be a similar study of approximately 100 patients in morphologically relapse at sites in the US and Europe. The primary endpoint will be overall complete response rate. Secondary endpoints will include MRD negative complete response and event-free survival. We're targeting the second half of 2021 for a BLA filing.

The trial will be a single arm.

Study of approximately 100 patients in morphologically relapse amongst sites in the U.S. and Europe. The primary endpoint will be overall complete response rate secondary endpoints will include MRT negative complete response and event free survival, we're targeting second half of Twentytwenty long frisbee late filing.

Christian Martin Itin: Moving to slide 11, our program in diffuse large B cell lymphoma. We believe that DLBCL is a large commercial opportunity, and given the market size and aggressive nature of this disease, LBCL is the most common type of Nahajan lymphoma, with approximately 25,000 patients diagnosed every year in the U.S. alone. High-dose chemotherapy combined with a monoclonal antibody led to remission in about 50% to 60% of the patients. Thus, we expect that the addressable population will be approximately 10,000 patients in the U.S. and EU5 combined. DLDCL represents an aggressive and rapidly progressing cancer.

Moving to slide 11, I program in diffuse large b cell lymphoma, we believe that the RBC is a large commercial opportunity given the market size aggressive nature of this disease.

The L.D.C.L. is the most common type of my Hodgkin lymphoma, with approximately 25000 patients diagnosed every year and the U.S. Hello.

Hi dose chemotherapy combined with a monoclonal antibody, let to remission in about 50% to 60% of the patients. That's we expect that the addressable population to be ex proximately 10000 patients in the U.S. and to utilize combined.

Yeah, Bcl represents an aggressive rapidly progressing cancer for patients who relapsed.

Christian Martin Itin: For patients who relapse or are refractory to first-line therapy, the current standard of care for second-line therapy consists of a platinum-based chemotherapy regimen with rituximab. Patients who respond to second-line therapy may go on to receive autologous hematopoietic stem cell transplantation, or HSCT. Patients who are not candidates for HSCT are those who do not respond to second-line therapy or who relapse after HSCT. Patients who are not candidates for HSCT are typically treated with third-line salvage chemotherapy.

For our refractory to first line therapy. The current standard of care for second line therapy consists of platinum based chemotherapy regimen with my talks about patients respond to second line therapy may get along to receive autologous hematopoietic stem cell transplant or HSC tea.

Patients were not candidates for HSC to eat or are those who do not respond to second line therapy or relapsed. After HCT are typically treated with the third line salvage chemotherapy.

These patients have a corporate proceeds and treatment is generally palliative to try to prevent further cancer growth without you intend to cure.

There are two approved karkhi products available today, yet here there remains a high unmet need despite highly active seasonality car T therapy in the relapsed refractory setting most of the responses are not durable and toxicity limits broad application, particularly the outpatient setting.

Christian Martin Itin: These patients have a poor prognosis, and treatment is generally palliative to try to prevent further cancer growth without intent to cure. There are two approved CAR T products available today, yet here there remains a high unmet need. Despite highly active C90 CAR T therapies in the relapsed refractory setting, most of the responses are not durable, and toxicity limits broad application, particularly in the outpatient setting. Turning to slide number 12, we highlight the current state status of CAR T-cell therapies in DLBCL. Despite an objective response rate of 70% to 80% and high-based PR rates of 40% to 55%, only 29% to 37% of the patients achieve a durable complete remission in DLBCL. Additionally, approximately a third of the CRs are lost over time, and loss of CRs is caused by PD-L1-UP regulation, which contributes to CAR-T exhaustion and CD19 antigen loss. Safety is also an issue with high rates of severe cytokine release syndrome of 13 to 22% and severe neurotoxicity of 12 to 28%. The early onset and severity of toxicities require intensive inpatient management. Moving to slide 13.

Turning to slide number 12, we highlight the current state status of car T cell therapies and deal DCIO. Despite an objective response rate of 70% to 80% on high base CR rates of 40% to 55%.

Only 29% to 37% all the patients achieve a durable complete information that deal PCL.

Approximately a third off the C. Ours are lost over time and also see ours, our cost by PD, along up regulation, which contributes to car T exhaustion of Cdnineteen attitude evolved.

Safety is also an issue with high rates of size severe cytokine release syndrome of 13% to 22% and superior to toxicity, 12% to 28%.

Early onset and severity of toxicities requires intensive inpatient management.

Moving to slide 30, the profile the desired features of car T necessary to target a broad use across all settings of care, including as outpatient therapy. Key features include high sustained complete response by preventing target exited relapse I'm checkpoint mediated resistance as well as low severe crs without intensive manner.

Ben and low neurotoxicity raise the latter safety profile elements lending themselves to say to use.

Christian Martin Itin: We profile the desired features of CAR-T necessary to target a broad use across all settings of care, including as outpatient therapy. Key features include high sustained complete response rates, preventing target negative relapse and checkpoint mediator resistance, as well as low severe CRS without intensive management and low neurotoxicity rates. The latter safety profile elements lend themselves to use that would not require intensive management of these patients and ultimately may allow you to actually treat these patients in an outpatient setting and avoid readmissions of those patients back to the hospital. Continuing to slide 14, you can see that we have designed a product in Auto 3 that targets a total addressable relapsed refractory DLBCL patient pool far exceeding those that can be reached by the approved products.

That would not require intensive.

Management of these patients and ultimately may allow you to actually treat these patients get an outpatient setting and to what we admissions of those patients back at the hospital.

Continuing to slide 40, you can see that we have designed to product in order for either targets a total addressable relapsed refractory he obese patient pool far exceeding those that can be reached by the approved products patients received the approved products as the most part is inpatient and centers of excellence because of the high rate and severity of toxicities and its touched.

<unk> market opportunity is limited to approximately 20% of the patients.

For treating be centers.

Even smaller groupings of patients that are eligible for approve car T products. However, with minimal talks management of older. Three this would allow treatment across all settings of care across increasing healthcare utilization of our product candidate and growing the addressable market maximizing reimbursement auctions compared to approved products.

Christian Martin Itin: Patients receive the approved products for the most part as inpatients in centers of excellence because of the high rate and severity of toxicities. And as such, the market opportunity is limited to approximately 20% of the patients that are treated in these centers and even smaller groupings of patients that are eligible for approved CAR T products. However, with minimal tox management of auto three, this would allow treatment across all settings of care, increasing healthcare utilization of our product candidates and growing the addressable market and maximizing reimbursement options compared to approved products. We now move to slide 15.

We now move to slide 15, we highlight the preliminary efficacy that presented at each day.

As off.

The data cut off of January 21, 2020 in the courts dose at 450 million sells a hold or three plus pembrolizumab five to seven patients and chief that response and four to seven patients achieved complete response.

Turning to slide 16, we showed that across all those old dose levels seven out of a complete responders had ongoing complete responses to the median follow up about six month range. If one wants to 18 month old.

Christian Martin Itin: We highlight the preliminary efficacy represented at EHA. As of the data cutoff of January 21, 2020, in the cohorts dosed at 450 million cells of order 3, plus pembrolizumab, 5 out of 7 patients achieved a response, and 4 out of 7 patients achieved a complete response. Turning to slide 16, we show that across all those levels, seven out of eight complete responders had ongoing and complete responses at a median follow-up of up to six months, a range of one month to 18 months. Additionally, all seven out of seven complete responders treated with Auto3 and Pembrolizumab have ongoing complete responses as of January 21, 2020, at a median follow-up of three months, a range of one to 18 months. Looking at slide 17, order 3 continues to demonstrate a safety profile much like the desired profile we described earlier, which may allow use in a large outpatient setting. Additionally, no patients experienced grade 3 or higher cytokine release syndrome were reported with primary treatment.

All seven I Oh, seven out of several complete responders treated with older fleet and Pembrolizumab have ongoing complete responses as of January 21st 2020 at a median follow up all three months a range of want to 18 months.

Looking at Slide 17, all the three continues to demonstrate a safety profile much like the desire profile. We described earlier, which may allow used in the larger outpatient setting no patients experienced great for your higher cytokine release syndrome syndrome or reported with a primary treatment and also off the data cut off note patient has it.

We are engineered toxicity of any great in courts treated it all the three and Pembrolizumab.

You will see this compares very favorable favorably to other car T therapy, both improved and in development across the competitive landscape.

Overall I summarized on slide 18, we're very pleased to the profile of all the three to date has successfully manufactured product for all patients from the cell and gene therapy kind of pulled it Stevenage and the other three program is on track for decision mid next year I made the middle of this year could last a program into phase two.

On slide 19, Albert's Ah I would like to conclude with a brief discussion of two other programs in our pipeline because they have the potential to bring additional value inflection 2020 and beyond.

Christian Martin Itin: And as of the data cutoff, no patient has experienced neurotoxicity of any grade in cohorts treated with order 3 and pembrolizumab. You will see this compares very favorably to other CAR T therapies both approved and in development across the competitor landscape. Overall, as summarized in slide 18, we are very pleased with the profile of Auto3 to date.

Slide 19, we highlight our unique targeting approach at T cell lymphoma.

Been able to decipher very small differences and the amino acid sequence of the T cell receptor better chain.

Constant domain such that we identified.

Two mutually exclusive receptors, which can be individual targeted by the anti bodies unique to the specific subtype.

Unlike b cell approaches and individual I cannot leave without that T cells and therefore this approach allows us to salvage itself type of T cells likely to represent an equal proportion into Bobby in order to restore functionally insistent.

Christian Martin Itin: It successfully manufactured product for all patients from the cell and gene therapy catapult at Stevenage, and the Auto3 program is on track for a decision in the middle of this year to advance the program to phase 2. On slide 19 onwards, I would like to conclude with a brief discussion of two other programs in our pipeline because they have the potential to bring additional value inflection in 2020 and beyond. Slide 19, we highlight our unique targeting approach in T cell lymphoma. We've been able to decipher very small differences in the amino acid sequence of the T cell receptor beta chain, constant domain, such that we identify two mutually exclusive receptors which can be individually targeted by an antibody unique to the specific subtype.

Moving to slide 20 recently revealed the clinical outcome of patient long, which despite having be treated a lowest I was just 25 million car T cells showed a complete metabolic response.

Patient subsequently had progression on a Saturday, while patient enrollment in our phase one study what is the more advanced product all before targeting tier BC. One is ongoing with supply from the kind of pulled as a result, we expect to present initial phase one data by the end of Twentytwenty. They remain very excited about this program and the opportunity to.

Christian Martin Itin: Unlike B cell approaches, an individual cannot live without their T cells, and therefore this approach allows us to salvage a subtype of T cells likely to represent an equal proportion in the body in order to restore a functional immune system. Moving to slide 20, we recently revealed the clinical outcome of patient 1, who, despite having been treated at the lowest dose of 25 million CAR-K cells, showed a complete metabolic response. The patient subsequently had progression on day 71. Patient enrollment in our Phase 1 study with the more advanced product of a four-targeting TRBC1 is ongoing with supply from the catapult. As a result, we expect to present initial Phase 1 data by the end of 2020.

Progress and other specifically tailored product utilizing our advanced modular approach to disease, setting where no other car T I a product auction exist.

Finally on slide 21 through 23, we summarize some important points from our lead program in solid tumors focusing on slide 21 solid tumors have remained challenging area for advancement to settle the therapies due to the complexity of the micro environment and the ability to target disease specific antigen Autistics HDD too.

Targeted therapy has been encouraging.

As has shown encouraging preliminary data demonstrating initial anti tumor activity, giving us confidence that this target is an interesting and relevant target to pursue.

Turning to slide 22.

We do our attention to our modular approach to enhance all the six LNG for the solid tumor micro environment, we have impaired our next generation product to tackle the key areas to have previously been shown to hamper responses in the solid tumor environment. All the six and she leverage is the same TD to targeting coffee, but increased persistence.

Christian Martin Itin: We remain very excited about this program and the opportunity to progress another specifically tailored product utilizing our advanced modular approach to a disease setting where no other CAR-T product option exists. Finally, on slides 21 through 23, we summarize some important points from our LEAP program in solid tumors. Focusing on slide 21, solid tumors have remained a challenging area for the advancement of cellular therapies due to the complexity of the microenvironment and the ability to target disease-specific antigens. Auto 6, a GD2 targeted therapy, has shown encouraging preliminary data demonstrating initial antitumor activity, giving us confidence that this target is an interesting and relevant target to pursue. Turning to slide 22, we draw our attention to our modular approach to enhance Auto6NG for the solid tumor microenvironment. We have empowered our next generation product to tackle the key areas that have previously been shown to hamper responses in the solid tumor environment. Auto6NG leverages the same GD2 targeting CAR-T, but it increased persistence and also improved the persistence as well as helped the cells survive in a checkpoint-rich and TGF-beta-rich environment.

And also improve the persistence as well as helped the cells survive a checkpoint rich and TGF beta rich environment. This product has been specifically designed to address the precisions control tumor defenses.

Turning to slide 23, a fixed fee we were excited to reveal data showing that the additional of the that's the addition of these modules to the ought to six energy product for shown to augment is functions by extending T cell persistence and rendering modified T cells position to both TGF beta and PD, one PD, along driven immune inhibition in vitro they've also revealed.

The clinical outcome of patient bomb in our phase long program, despite being treated at least I was demonstrated carter and its off activity.

I believe although six ngs position for additional value inflection as we commenced phase one study second half of 2020.

With that I will turn over the coal to Andrew for our third quarter 2019 International uptake Andrew.

Hi, Thanks, Christian and Doug Good morning, Alright, good afternoon to everyone.

Christian Martin Itin: This product has been specifically designed to address the persistence, control tumor defense, Turning to slide 23, at this seat, we were excited to reveal data showing that the addition of these modules to the Auto6MG product was shown to augment its functions by extending T cell persistence and rendering modified T cells resistant to both TGS-beta and PD-1, PD-L1-driven immune inhibition in vitro. They've also revealed that the clinical outcome of patient 1 in our Phase 1 program, despite being treated at the lowest dose, demonstrated encouraging evidence of activity. We believe that 6MG is positioned for additional value inflection as we commence the Phase 1 study in the second half of 2020. With that, I will turn over the call to Andrew for our third quarter 2019 financial update. Andrew.

It's my pleasure to review our financial results for the full year January through December of 2000, and non team and we're on slide 25 total net total operating expenses for the 12 month. Peter in 31 December 2019, or 146 million that was native grant income of 2.9.

Million dollars that compares to net operating expenses are $74.1 million also net of grant income of $1.5 million for the same period.

The increase in turn in total net operating expenses was due in general to the increase in development activity to support the advancement that product candidates increased headcount, primarily you know development manufacturing functions as well as to cost of being a public company.

Andrew Oakley: Thanks Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the full year January through December of 2019, and we are on slide 25. Net total operating expenses for the 12-month period ending on 31 December 2019 were $146 million, and that was net grant income of $2.9 million. That compares to net operating expenses of $74.1 million, also net of grant income of $1.5 million for the same period. The increase in total net operating expenses was due, in general, to the increase in development activity to support the advancement of our product candidates, increased headcount primarily in our development and manufacturing functions, as well as the cost of being a public company.

Research and development expenses increased to $105.4 million for the year ending December 31, 2019 from $48.3 million for the year in 30 by December 2018.

Cash costs, which exclude depreciation as well as share based compensation increased to 83.4 million from 41.5 million increase in research and development costs of $41.9 million consist primarily of an increase in compensation related costs of $20 million.

Primarily due to an increase in headcount to support the advancement of our product candidates in clinical development and investment in Minot factoring facilities and equipment I.

An increase of $4.1 million in resurgent manufacturing consumables in part due to the migration expansion of our research and process development borrowed trees.

Andrew Oakley: Thank you. Research and development expenses increased to $105.4 million for the year ending December 31, 2019 from $48.3 million for the year ending 31 December 2018. Cash costs, which exclude depreciation as well as share-based compensation, increased to $83.4 million from $41.5 million.

First house to a new location in the media works facility preparations in advance of any potential disruption to supply arrangements that may occur due to Brexit as well as validation and training costs as part of the start up at the catapult facility.

An increase of $10.2 million in facility costs, primarily related to two increased a number of facilities, mainly a it mediaworks and catapult an increased $3.8 million in project expenses related to activities to prepare activate and monitor clinical trial programs and an increase in.

Andrew Oakley: The increase in research and development costs of $41.9 million consisted primarily of an increase in compensation-related costs of $20 million, primarily due to an increase in headcount to support the advancement of our product candidates in clinical development and investment in manufacturing facilities and equipment. An increase of $4.1 million in research and manufacturing consumables, in part due to the migration and expansion of our research and process development laboratories from Forest House to our new location in the United States. An increase in research and development costs of $4.1 million for moving research and development facilities from Forest House to our new location in the MediaWorks facility. Preparations in advance of any potential disruption to supply arrangements that may occur due to Brexit, as well as validation and training costs as part of the startup at the Catapult facility. An increase of $10.2 million in facility costs, primarily related to an increased number of facilities, mainly at MediaWorks and at Catapult.

Yeah, and legal and professional fees that includes a decrease in milestone payments of zero point $5 million, consisting of a milestone payment shock to to USIO business ill say of $2 million in 2019 and amounts due and payable to noise immunity.

Biotech.

In the current year as well as an increase in on a change in office expenses as well to render them.

General and administrative expenses increased $39.5 million year ended 31 December 2019 from 27.3 million for the year ended 31 December 2018 cash cost in this area, which exclude depreciation as well as share based compensation increased to $26.6 million from 20.

$1.4 million increased $5.2 million consisted primarily of an increase in compensation related costs of 2.6 million due to an overall increase in head count an increase of 1.9 million dollar in commercial activities at an increase in in public company compliance costs of around $1 million.

Andrew Oakley: An increase of $3.8 million in project expenses related to activities to prepare, activate, and develop. An increase of $3.8 million in research and development costs, primarily related to an increased number of facilities, mainly at MediaWorks and at Catapult, and legal and professional fees, which includes a decrease in milestone payments of $0.5 million consisting of a milestone payment to UCL Business PLC of $2 million in 2018 and a milestone payable to Norley Mutant Biotech in the current year as well as an increase in IT and general office expenses as well General administrative expenses increased to $39.5 million for the year ended 31 December 2019 from $27.3 million for the year ended 31 December 2018. Cash costs in this area, which exclude depreciation as well as share-based compensation, increased to $26.6 million from $21.4 million.

I think increase of zero point $7 million in facility costs, and which this was offset by a decrease of 1 million I teach charges and other office expenses.

Net loss attributable to ordinary shareholders was $123.8 million for the 12 month period compared to $57.8 million for the same timeframe in 2018, the basic and diluted net loss to ordinary share for the 12 months ended 31 December 2019 totaled 2.8 $8.

Compared to a basic and diluted net loss per share ordinary share of $1.48 for the 12 months ending sitting on December 2018.

Andrew Oakley: The increase of $5.2 million consisted primarily of an increase in compensation-related costs of $2.6 million due to an overall increase in headcount, an increase of $1.9 million in commercial activities, and an increase in public company compliance costs of around $1 million. An increase of $0.7 million in facility costs, and this was offset by a decrease of $1 million in IT charges and other office expenses. Net loss attributable to ordinary shareholders was $123.8 million for the 12-month period compared to $57.8 million for the same time frame in 2018. The basic and diluted net loss per ordinary share for the 12-month ended 31 December 2019 totaled $2.88 compared to a basic and diluted net loss per share, ordinary share of $1.48 for the 12-months ending 31 December 2018.

Cash and cash equivalents at the end of the the period totaled $210.6 million and that compares with 217.5 million at the end of December 2018, adjusting for the recent follow on offering in January when we raised.

Gross proceeds of set of $80 million.

Our cash at the end of January approximately stood at around $286 million and we anticipate that cash on hand provides us with the runway into 2022.

With that I will now hand to pull back to Christian to give you a brief outlook on expected.

Bostons Christian Thanks, Andrew Let me conclude this part of the management discussion with a review of the upcoming milestones that news flow through Twentytwenty, let's move to slide 27, the upcoming nine months will be an eventful period for us with multiple clinical milestones and opportunities for value creation.

Andrew Oakley: Cash and cash equivalents at the end of the period total $210.6 million, and that compares with $217.5 million at the end of December 2018. Adjusting for the recent follow-on offering in January, where we raised gross proceeds of $80 million. Our cash at the end of January stood at around $286 million, and we anticipate that that cash on hand will provide us with a runway into 2022. With that, I will now hand the call back to Christian to give you a brief outlook on expected milestones. Christian

Our chief operational focus will be commencing the registration trial for all along is that all the 11 you can U.S.. We also expect to report data across multiple programs and to progress the number of our other clinical trial candidates specifically updates on our ongoing clinical trials initiation of phase one study a volatile on LNG and pediatric JLL and first.

Half of this year I go no go decision on phase two initiation about a three and deal Bcl middle of this year initiation of phase one study autistics LNG toward neuroblastoma towards the end of this year and initiation initiation of phase one study over the next generation program in multiple myeloma.

Christian Martin Itin: Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through 2020. Now, we move to slide 27.

Total eight also towards the end of 2020.

Christian Martin Itin: The upcoming nine months will be an eventful period for us with multiple clinical milestones and opportunities for value creation. Our chief operational focus will be commencing the registration trial for Auto 1 in adult ALL in the UK and US. We also expect to report data across multiple programs and to progress a number of our other clinical trial candidates, specifically updates on our ongoing clinical trials, initiation of a Phase 1 study of Auto 1 in gene pediatric ALL in the first half of this year, a go-no-go decision on Phase 2 initiation of Auto 3 in DLBCL in the middle of this year, initiation of a Phase 1 study of Auto 6-MG in neuroblastoma towards In conclusion, on slide 28, I'd like to recap the major messages from today's call. First, Auto 1 is our foundational program, and first, Auto 1 is a program expected to move into the pivotal stage.

As well as.

Working on some exploratory clinical trials towards allogeneic approaches as well.

In conclusion on slide 28, I'd like to recap the major mesh messages from today's call first auto long. These are foundational program and first of all this program expected to move into pivotal stage, given the positive safety and efficacy profile today, we believe that all along has the potential to be a best in class Cdnineteen car T. In AOL secondly.

Our next priorities on auto three and deal Bcl, which obviously is expected and slated for clinical data on middle of the year. We expect to report full phase one data for all the three middle of 30 20 to reach a decision point.

For face to face to the trial initiation thereafter.

Looking ahead to the remainder of the year, we see opportunity for additional value steps for T cell lymphoma as well as.

The obviously start for the auto six next generation program targeting Ci to positive tumors. The company has a strong balance sheet with 286 million in cash which for the price of on rate into Twentytwenty too and finally, we're looking forward to see many of you got the upcoming HCR ASCO and Ajay meeting over the upcoming few.

A month and there are not happy to take questions. Operator. Please open the line. Thank you.

Ladies and gentlemen, if you have a question or comment at this time. Please proceed to starve them in one key on your Touchtone telephone. If your question has been introduced moves off from acute please press the pound speed.

Christian Martin Itin: Given the positive safety and efficacy profile today, we believe that Auto 1 has the potential to be the best in class CD19 CAR T in ALL. Secondly, our next priority is Auto 3 in DLBCL, which is obviously expected and slated for clinical data in the middle of the year. We expect to report full phase 1 data for Auto 3 in the middle of 2020 to reach a decision point for phase 2 trial initiation thereafter. Looking ahead to the remainder of the year, we see opportunity for additional value steps for T-cell lymphoma, as well as the start of the Auto6 Next Generation Program targeting GD2 positive tumors. The company has a strong balance sheet with $286 million in cash, which will raise the run rate into 2022. And finally, we're looking forward to seeing many of you at the upcoming AACR, ASCO, and EHA meetings over the next few months, and are now happy to take questions. Operator, please open the line.

First question comes from time to turn it by the way with H.C. Wainwright.

Hi, Good afternoon Christian Andrew Thanks for taking the questions. So I've a question on the barriers Oh. This is Aaron on for Debjit by the way. This is a I have a question on the barriers to outpatient treatment with auto Cartesian deal Bcl.

So we were looking at a steady in which they treated patients for the median of only two prior lines with license out and in outpatient setting and they ended up hospitalizing, 59% of the patients at the first started crs or neurotoxin.

So what do you think would be a reasonable level of hospitalization that could warrant expansion to the outpatient setting and do you think that there could be more competition in certain subsets of patients in the outpatient setting for various auto crises.

So a very good question, Aaron and it's obviously, a very interesting kind of analyses. When you look at the field what you realize that approximately at this point only about 20 for trend 20% of the patient sort of can be targeted with car T therapy in the current settings, which is really focused on the centers of excellence and the.

Operator: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press the star and then the one key on your touchtone telephone. If your question has been answered or you wish to move yourself from the queue, please press the pound key.

Reason for that is predominantly driven by the requirement for fairly intense management off these patients to deal with the adverse event profile for the current product path and what do you basically quoted a that basically flux of patients back into the hospitals that were considered initially to be treated in I pay.

Operator: Our first question comes from Deb Chichetta, by the way, with AC Wayne. Hi Christian, Andrew. Thanks for taking the questions. So, I have a question on the barriers.

Aaron: Oh, this is Aaron from Deptid, by the way. I have a question on the barriers to outpatient treatment with autocartes and DLVCL. So we were looking at a study in which they treated patients with a median of only two prior lines with lysocell in an outpatient setting, and they ended up hospitalizing 59% of the patients at the first sign of CRS or neurotoxicity. So what do you think would be a reasonable level of hospitalization that could warrant expansion to the outpatient setting? And do you think that there could be more competition for certain subsets of patients in the outpatient setting for various autocracies?

Setting just indicate the need for significant level of management of these patients to begin ways and that the fundamental property of the product itself.

I think is shared by all of the current products that are either being approved or back to be approved.

So what what I think we're highlighting in our presentation is that the audit free at this point.

Showing no high grade tie to kind of release syndrome and that they did not require actuals and management of the patient. So we didnt actually have to put steroids in.

Recovering or we have didnt have to quote socialism abbvie. These in these patients as a preventative measure a management measures. This is the data actually from manage patients.

Christian Martin Itin: So, a very good question, Aaron, and it's obviously a very interesting kind of analysis when you look at the field where you realize that, at this point, only about 20% of the patients can be targeted with CAR T therapy in the current settings, which are really focused on the centers of excellence. And the reason for that is predominantly driven by the requirement for fairly intense management of these patients to deal with the adverse event profiles that the current products have. And what he basically quoted, that basically flux of patients back into the hospital that were considered initially to be treated in an outpatient setting, just indicates the need for a significant level of management of these patients to begin with. And that's a fundamental property of the product itself and one that I think is shared by all of the current products that have either been approved or are about to be approved.

What was probably more surprising and obviously I have a remarkable outcome.

The fact that we have seen no neurotoxicity of any great into patients that we have treated in combo in combination with pembro across a set of off dose levels and that is truly surprising because none of the programs targeting redirecting T cells targeting cdnineteen to date has shown a.

These type of the feature all of them actually have.

On a neurotoxicity asset as a core type of adverse events that they do experience. The fact that we have seen mountain without managing the patients gives us a lot of confidence that we have a type of profile that should be well manageable.

Also in an outpatient setting and also importantly in centers that are not the few centers of excellence in the country, but also much more broadly in the periphery right fact, most of the obese patients do get treated at the last and I think thats going to be a core feature for the program and to date, what we've seen as approach.

Well certainly has not been reported by any or anyone else within the field.

And.

Great. Thank you.

[noise] that Karen.

Our next question comes from Chad Messer Needham <unk> company.

Christian Martin Itin: So what I think we were highlighting in our presentation is that the auto three, at this point, has shown no high-grade cytokine release syndrome, and this did not require actual management of the patient. So we didn't actually have to put Steric in, Steri-Cov-Rin, or we didn't have to put Tocilizumab in these patients as a preventative measure, or as a management measure. This is data actually from unmanaged patients. What was probably more surprising and obviously a remarkable outcome was the fact that we have seen no neurotoxicity of any grade in the patients that we have treated in combination with PEMBRA across a set of those levels. And that is truly surprising because none of the programs targeting redirecting T-cells targeting CD19 to date have shown this type of feature.

Right.

Good day at all thanks for taking my questions.

Maybe just to start by continuing a little bit to be discussed we're just happening on on.

Autos, three and safety you've got to go no decision coming up.

He is there an actual bar there you can describe I mean zero percent would be awesome, but maybe not.

All that Pratt practical to hold onto.

I think if you have a low level off of Neurotox low rate neuro talks at a low level I think that would be very bell manageable. We also true remember that the patients treated with planet idling side to actually our pay are treated eight and outpatient setting and our managed that way so and.

Christian Martin Itin: All of them actually have neurotoxicity as a core type of adverse event that they do experience. The fact that we have seen none without managing the patients gives us a lot of confidence that we have a type of profile that should be well manageable also in an outpatient setting and also, importantly, in centers that are not the few centers of excellence in the country but also much more broadly in the periphery, where, in fact, most of the DLBCL patients do get treated in the U.S. And I think that's going to be a And to date, what we've seen as a problem, and the reason for that is that the profile certainly has not been reported by anyone else within the field.

The the Neurotox Ray dollar superbly insight is not zero.

But it is less than 10, instead, what we see but a card fees that are currently.

Currently gone through approval or close to approval.

And so there's clearly a bar here that is is not a zero number but definitely want to see a lower level of neurotoxicity of you want to avoid high grade cytokine release syndrome, which is really requires it to go back into the hospital.

Okay, and then just begin thinking on efficacy and safety bars on the auto for program I mean for T cell lymphomas, we don't have good standard a character to compare ourselves up against so what do you what do you what do we need to see later this year for auto for.

Operator: Great, thank you. Thank you. Our next question comes from Chad Messer with Needed, Good day to all.

Chad Messer: Thanks for taking my questions. Maybe we just start by continuing a little bit the discussion we were just having about Auto 3 and safety. We've got a go-no decision coming up. Is there an actual bar there you can describe?

In order to to get excited and optimistic about that one [noise].

I think what we would like to see I just want to see a good level of responses in those patients and and evidence that we start to see also at reasonable level off persistence. So we get some durability those responses as you point out. This is a very devastating disease, there's very little options at this point.

Christian Martin Itin: I mean, 0% would be awesome, but maybe not all that practical to hold on to. I think if you had a low level of neurotox, a low rate neurotox at a low level, I think that would be very well managed. We also should remember that the patients treated with Blincyte are treated in an outpatient setting and are managed that way. And the neurotox rate, obviously, for Blincyte is not zero.

And I think a program that gives you a reasonable level of remissions in these patients together with some durability of response will go a long way.

And clearly the bar for this for for this indication is lower than what we're seeing in lymphoma, certainly much lower than what we're seeing a lucky yet.

Christian Martin Itin: But it is less intense than what we see with the CAR-Ts that have currently gone through approval or are close to approval. And so there is clearly a bar here that is not a zero number, but we definitely want to see a low level of neurotoxicity. And you want to avoid high-grade cytokine release syndrome, which really requires you to go back into the hospital. Okay, and then just again thinking about efficacy and safety bars on the Auto 4 program. I mean, for T-cell lymphomas, we don't have a good standard of care to compare ourselves to. So what do we need to see later this year for Auto 4 in order to... get excited and optimistic about that one?

Alright, great will banks were looking forward to all the data you guys coming up this year.

Excellent thanks for joining Jeff.

Our next question comes from burn in minutes Jefferies.

Hi, guys. Thanks for taking my questions Christian on auto to can you just give us a status update on the energy program there.

With multiple myeloma, obviously went back and Reengineered, a new program, which is called overweight and that programming slate it to get back into the clinic second half of this year.

Got it and then auto for.

Thanks for the prior response, but if I if I look at some of the data with Bendamustine for example in relapsed refractory setting I think.

There's some data out there that reports in or close to 30% CR about 20, 25% median dior about 3.3 modules that kinda like the bar that you would need to be with auto for.

Christian Martin Itin: I think what we would like to see is a good level of responses in those patients and evidence that we start to see also a reasonable level of persistence, so we get some durability of those responses. As you point out, this is a very devastating disease. There are very few options at this point.

I think you want to be above that but you're right that is currently what the bar looks like in that disease setting.

That is sort of us as the kind of the best we can do for these patients at this point.

So clearly want him.

Ray side, but it's a it's clearly a very poor starting point.

Christian Martin Itin: And I think a program that gives you a reasonable level of remissions in these patients, together with some durability of response, will go a long way. And clearly, the bar for this indication is lower than what we're seeing in lymphoma and certainly much lower than what we're seeing in leukemia. All right, great. Well, thanks. We're looking forward to all the data you guys have coming out this year. Excellent. Thanks for joining us, Jeff.

Okay, and then maybe it would just a question on auto three.

How much data do we need to see later this year to move this program into pivotal.

Do you know and I guess, what cell dose are you looking at.

Greater than 150 million cell dose or are you looking at the 450 million cell dose to make a determination on on pivotal studies there.

Operator: Our next question comes from Byron Aminuchuk. Hi guys, thanks for taking my questions. Christian, on Auto 2, can you just give us a status update on the NG program there? With multiple myeloma, obviously, we went back and re-engineered a new program, which is called AutoAid, and that program is slated to get back into the clinic in the second half of this year. Got it.

So we're clearly looking at that at a at this point a greater of 150 retreating at 450, and we'll have to see kind of had the dose level to differentiate if they do much at this point.

And we want to see a sustained CR rate of 50% plus index population.

50% plus sustain meeting greater than six months.

Or greater than three months.

Byron Aminuchuk: And then on Auto4, thanks for the prior response. But if I look at some of the data with bendamustine, for example, in relapsed refractory setting, I think there's some data out there that reports an OR close to 30%, CR about 20%, 25%, and median DOR about 3.3 months. Is that kind of like the bar that you would need to beat with Auto4?

Great. Thank you.

Thank you.

Your next question comes from match this with William Blair.

Hi, Thanks for taking my questions guys. So two questions on auto one first for the pivotal trial. How are you thinking about the criteria for baseline blast counts scenario, you're going to do split dosing based on blast counts and a pivotal trial there.

Christian Martin Itin: I think you want to be above that, but you're right. That is currently what the bar looks like in that disease setting. That is sort of the best we can do for these patients at this point. So you clearly want to move to the CRA side, but it's clearly a very poor starting point.

Was there any difference in kind of outcomes for that in the original all car study and then in the trial what kind of health economic data do you think is particularly important.

Christian Martin Itin: Okay, and then maybe just a question on Auto 3. How much data do we need to see later this year to move this program into pivotal, you know, and I guess at what cell dose?

When you go to hospital administrators here in the U.S., there's been quite a lot coming out recently about.

Christian Martin Itin: Are you looking at, you know, greater than 150 million cell doses, or are you looking at the 450 million cell dose to make a determination on pivotal studies there? So we're clearly looking at this point at greater than 150, we're treating at 450, and we'll have to see kind of how those levels do differentiate if they do much at this point. And we want to see a sustained CRA to 50% plus in this population, with 50% plus the stay-in meeting for greater than six months. Greater than three months.

The cost the rescue medications are looking at I see you days or.

Potential to get it outpatient by not getting something like Crs or something it causes how pigeon have to go to the hospital for a certain number of days I guess, what do you. What do you think is most important there amongst all these different.

Let me kind of health economic endpoints are being looked at.

Right. So first of all thanks for joining that.

With regards to the the tumor lever to tumor burden of these patients at these are patients actually are in relapse morphological read apps, which means that they have 5% of more of the or more blasting tomorrow.

Christian Martin Itin: Great, thank you. Thank you. Our next question comes from Matt Fist with William Blair.

Operator: Hi, thanks for taking my questions, guys. So two questions on Auto One. First, for the pivotal trial, how are you thinking about the criteria for baseline blast counts? And are you going to do split dosing based on blast counts in a pivotal trial there? Was there any difference in outcomes for that in the original all-car study?

That's the first I think answer to your question. The second answer is with regards.

To the approach to dosing, we're going to use the same dosing that we have used for the whole car 19 study to phase one study, which is that we look at a cut off of 20% blast. If we are if the patient is above 20% last we do a dose reduction and we give a lower for initial dose off the product.

Matthew Gitlin: And then in the trial, what kind of health economic data do you think is particularly important when you go to talk to hospital administrators here in the U.S.? There's been quite a lot coming out recently about the cost of rescue medications or looking at ICU days or the potential to get an outpatient by not getting something like CRS or something that causes a patient to have to go to the hospital for a certain number of days. What do you think is most important there amongst all these different kinds of health economic endpoints that are being looked at? Right, so first of all, thanks for joining us, Matt.

To sort of manage the kinetics of the initial anti tumor activity, which is really what determines to a significant part the overall toxicity profile.

Into patients so, yes, there's going to be a very.

Tactical approach to these uses a phase one study.

With regards to auto won that kind of the yes parameters to drive.

Reimbursement and apps on I think it's important first of all to understand that this is a patient group.

Christian Martin Itin: With regard to the tumor burden of these patients, these are patients that are actually in relapse, in morphological relapse, which means that they have 5% or more blasts in the marrow. That's the first, I think, answer to your question. The second answer is with regard to the tumor burden. Thank you very much. Thank you. Manage them through infections and so on and so forth, which often requires ICU stays for these patients. So managing these patients through the final year of life is extremely costly and is costing the system money to date.

That obviously is very intensely managed to date in other words to treatment of adult MLL patients is very expensive.

Even if the outcome is debt.

It is a very extensive therapy, because you have to manage these patients due to their immune suppression quite frequently at the hospital.

Management managed them through infections that itself and so forth, which requires off nicely you stays for these patients. So managing these patients to the final year of life is extremely extremely costly and he's costing to system to date. So what we're doing with regards to collecting information. We're obviously collecting a very diligently information a core.

Christian Martin Itin: So what we're doing with regard to collecting information, we're obviously collecting very diligently information related to resource utilization across all the patients in the trial. And we also do record the information from a patient's perspective, with patient-reported outcomes as well. So we have both perspectives that we collect the data from, and that will also be built into the appropriate arguments for the respective payers. And as you know, depending on the healthcare system we're looking at, there are quite a few differences in what the various payer groups are actually looking for. Thanks, Christian.

Related to.

Resource utilization.

Across a across all the patients in the trial and we also do record the information also from a patient's perspective.

Patient reported outcomes as well so we have both perspectives that we collected data from and that will also be built and into the appropriate arguments.

For the respective payers and as you know depending on the health care system. We're looking at their quite differences on what the various various payer groups are actually looking for.

Thanks Christian good I, one follow up on the.

Christian Martin Itin: Could I ask one follow-up on the split dosing again? I know there were a couple of patients who had some neurotoxicity in the data presented today with Auto-1, and they had higher tumor burdens. Did those patients get the second half of the dose, or did the neurotoxicity occur with that first lower dose? It's typically linked to the initial expansion of the CAR T-cells, which is mostly driven by the first dose.

Split dosing again I know there were a couple of patients who had some no toxicity.

In the data presented today with auto one, though and they had higher tumor burden would the no tuck that those patients get the second half of the dose due to the neurotoxicity occur with that first lower dose.

It's typically linked to the initial expansion of the car T cells, which is mostly driven off the first dose.

And what we obviously have seen ace and Thats what are you referring to the extent the patients did actually developed a higher rate neurotoxicity with auto loans made this particularly indication.

We're all patients with very high tumor burden, we're looking at more than 50% tumor burden if these patients.

And all of them actually responded well to a dose steroids to actually get normalized.

Christian Martin Itin: So obviously, what we can do with these patients is we can actually give these patients steroid cover up front, given that we can identify the patients at risk here, and that should significantly reduce in a significant way the rate of high-grade neurotoxin in these patients. But there was a very clear population of cells that were at risk of neurotoxin, and that was straight linked to a very high tumor burden in the marrow. Thank you. Okay, thanks Matt. Our next question comes from Greg Sivanovich with Goldman Sachs. Hey, good morning, and good afternoon. Thanks for taking my questions. I've got three this morning, if you don't mind.

So obviously, what we can do with these patients whose we can actually get these patients.

A a a steroid cover upfront given that we kind I did identify the patients at risk leader and that should mitigate into significant way actually the rate of high grade talks in these patients, but there is very clear population of sales.

Our at risk.

Off.

And your talks and that was straight linked to very high tumor burden in tomorrow.

Yes. Thank you.

Okay. Thanks, Matt.

Your next question comes from Brexit recovered from Goldman Sachs.

[laughter].

Hey, good morning. Good afternoon. Thanks for taking my questions I've got three this morning, if you don't mind on my first.

Operator: My first question is, you've got a new program, which is an allogeneic approach, and so I'm just wondering what the thought process here is? What's the target product profile you're hoping to achieve? How is it different from other allogeneic approaches? So that's kind of all wrapped up in one question. My apologies for that.

Is a I noticed you've got to new program, which has an aloe generic approach and so I'm just wondering.

What's the thought process here, what's the target product profile, you're hoping to achieve has a different from from other allogeneic approaches. So that's kind of all wrapped up in one question. My apologies for that my second question just has to do with the Prime technology that should license last November if you just give us some more color.

Greg Sivanovich: My second question just has to do with the prime technology that you licensed last November; could you just give us some more color on that opportunity? And then my third question, if you could just provide some questions for Andrew, just on 2020 OpEx and how we should think about trends relative to how you finish the year in 2019. Thank you. Okay, all right. I'm happy to get started on the first two questions.

On on that opportunity and then my third question.

If you could just provide some odd question for Andrew just on 2020, Opex and how we should think about trends are relative to how you finished the area in 2019. Thank you.

Okay, all right I'm happy to get started on the first two questions. So the first question was related to the dimensional approaches to or it's a d. it towards allogeneic approaches obviously, the CF patients that are underserved either have a.

Christian Martin Itin: So the first question was related to the mention of approaches towards allergenic approaches. Obviously, if you have patients that are underserved, either have basically no usable T-cells that you can actually extract by leukophoresis, or are at such a speed of progression that you can't actually manufacture a product, that's obviously where you would like to have an alloproduct that could go in there, even if that alloproduct would be inferior to the normal products that we're producing. And so what we're looking at here is using basically the technology approach that we've been using, which is programming cells and changing behavior at the protein level, which is the basic foundation in terms of the technology that we're using. We're creating protein modules that change the behavior of cells. What we have outlined is one module that actually changes the expression of the T-cell receptor on the surface of the cells, prevents that from happening, and with that, obviously, you do prevent graft-versus-host disease.

Basically no usable T cells that he can actually extract value apheresis or are such a touch a speed of progression that he can actually manufactured product. That's obviously, where you would like to have an outlook product.

That could go in there even if that aloe product will be inferior to add an oral products are producing and so what we're looking here is a using basically the technology approach that we've been using which is programming to cells.

Changing behavior out the protein level, just the basic foundation in terms of technology, using recreating protein modules to change the behavior of cells.

What we have outlined is a is one module that actually changes on the expression of the T cell receptor on the surface of cells prevents that from happening our waste that obviously you do to prevent graft versus host disease. We're doing some initial clinical testing starting towards the end of this year together in a collaboration with one of our academic partners. So that's sort of moving.

Christian Martin Itin: We're doing some initial clinical testing starting towards the end of this year, in collaboration with one of our academic partners. So that's sort of moving us, technologically, towards an allergenic type of approach. So that's what we're doing there. It builds on the same way of programming. It builds on the same way of programming cells that we're doing, obviously, in general, and it avoids just the usual gene editing type of approaches that we've seen typically across the space by actually making the modifications at the cellular level, at the protein level in the cell.

Us towards technologically towards.

An outage snake type of approach so thats what were doing they're built from the same way of programming cells that we're doing obviously in general.

And it avoids just the usual gene editing type of approaches have you seen typically across the space, but actually making the modifications have to set little level protein leveling to sell.

Christian Martin Itin: The second question was related to the prime technology that we've been licensed to use, and that is, in essence, a technology that looks to address heterogeneity within solid tumors, and there are different types of heterogeneity, one of which is related to the fact that often a tumor is not homogeneous for a single target antigen. And in other words, you may have, if those of you who remember kind of the early HER2 stains when Herceptin came up, where you actually have, when you look at the slide stained with HER2 antibodies, you see actually kind of a very spotty staining, certain areas that are positive, but many areas that are either just barely positive or actually straight negative. So in other words, there's heterogeneity in terms of target expression, and that's quite common. This is not the case for GD2, which is one of the reasons why we're working with that particular antigen.

The second question was related to.

The prime technology that we've seen license and that is in essence of technology, where it that looks to address heterogeneity within solid tumors and theres sort of different types of heterogeneity, one of which is related to.

The fact that often a tumor is not homogeneous for single target antigen and in other words you may have if you thought it was if you remember kind of the early her to stains and Herceptin came up.

Where do you actually have asked when you look at the slide sustained by with her to antibodies to see actually kind of a very spotty staining certain areas that are positive many areas that right that just barely positive to actually straight negative. So in other words. This heterogeneity in terms of target expression and that's quite common.

It is not the case for Gd too, which is among the reasons are working with that particular outages, but where do you have heterogeneity. What do you would like to do as you'd like actually to take out to sell those with the target antigen of choice that you can identify but then also induce.

Andrew Oakley: But where you have heterogeneity, what you would like to do is you would like to actually take out the cells with the target antigen of choice that you can identify, but then also induce a natural immune response against the other parts of the tumor that are not positive, that are negative for the target antigen you can directly address with the CAR-T cell. The prime technology actually allows you to boost that natural immune response against the tumor, and that's what we're using with these modules. And with that, I think I'm handing over to Andrew. Sure. Thanks for the question, Greg. Look, I'm not quite sure that we're really in a position where we're going to get sort of too granular in terms of OPEC's guidance for the year.

A natural immune response against the other parts of the tumor that did not positive that a negative for the target at the gym you can directly address with the car T cell. The prime technology actually allows you to boost that natural immune response.

Towards the tumor and that's what we're using with these modules.

With that I think I'm heading over to Andrew.

Thanks, a question Greg.

I'm not quite sure that were really in a position that bigger so going to get sort of too granular in terms of opex guidance for the year.

Andrew Oakley: You know, our guidance is that the cash runway we've got will last into 22. In a practical sort of sense, if we look at sort of, you know, there are three sort of buckets of cash spend in terms of R&D, G&A, and CapEx itself. You know, you'll probably see an increase in all three categories during the course of 2020, but G&A, not too much. R&D, a reasonable sort of increase, but, you know, there were a lot of other costs.

And just the cash runway, we've talked last into into 22.

You know not practical sort of sense. If we if we look at sort of you know this three so you know buckets of of cash spend in terms of R&D, GE, and I and and and.

And and Capex. It so you probably see an increase in all three categories. During the course of the 2020, but.

Jeannine not not too much R&D reasonable sort of increase but but you know there were lot of some costs of in terms of the validation training and and set up as catapult sit in the 19 year that obviously want what occurred and 20, but will then be sort of offset by in terms of actual patient to push.

Andrew Oakley: So, in terms of the validation training and setting up of the catapult that in the 19 years, that obviously won't occur in 20, but will then be sort of offset by terms of actual patient processing or manufacturing. So, I think that's about as far as we want to go from a guidance perspective in relation to OPEC's for 20. You know, we'll just stick with the concept that we've got a cash runway until 22.

As you know manufacturing.

So I think that's at the moment about as far as we want to go from from a guidance perspective.

In relation to Opex for the 20.

Well just stick with the concept that we go to cash runway into 22.

Greg Sivanovich: Sure. Okay, that's appreciated. Thank you very much. All right. Thanks, Greg. Thanks for joining us. Our next question comes from Jim Berkner with Wells Fargo. Hello, good morning. It's Nick on for Jim this morning.

Okay. That's appreciate it thank you very much.

All right. Thanks, Greg Thanks for joining.

Our next question comes from June Birchmere with Wells Fargo.

Hi, Good morning, it's Nick competence morning.

Operator: I really just want to focus on Auto-One. Unfortunately, I joined the call a little late, so I apologize if my questions will be answered from your prepared comments. But as far as the CTA goes, that was filed over three months ago. Have you enrolled a patient in the UK into the registration studies? We're expecting enrollment to start actually this month in the UK. And then, as far as the U.S. goes, obviously, that's lagging in terms of the IND filing, but have you got sites identified ready to go? How many sites do you think you need for the trial? And is it feasible to warehouse patients? trial. So first of all, the U.S. I&D patent is expected to be filed this month.

Hi, I really would just want to focus on on auto one night. Unfortunately, I joined the call a little late so I apologize if my questions will be onset from your prepared comments, but as far as the Ceta goes that was filed over three months ago have you enroll the patients in the UK and into the registration study.

[laughter].

We're expecting enrollment starting actually this month in the UK.

And then as far as the U.S. galleries, obviously that that's lagging in terms of the R&D filing but have you got sites identified ready to go how many sites do you think you need for the trial and is it feasible to warehouse patience for this trial.

So first of all at the the a U.S. I'd is expected to be filed this month that will allow us to actually enroll and treat the first years patients in the second quarter, which is what we have guided to in which we're on track for.

Nick: That will allow us to actually enroll and treat the first U.S. patients in the second quarter, which is what we've guided to and which we're on track for. In terms of the clinical centers, yes, they're absolutely identified. We expect to have approximately 30 patients in – sorry, 30. We expect the majority of those centers, more than 20 in the US, the remainder in the UK and rest of Europe. So yes, all of those centers are obviously active, and we're in contracting processes, etc., as you would expect. Mm-hmm.

In terms of the clinical centers, yes. They are absolutely identified we expect to have approximately 30 patients and theres only 30.

Oh, we expect the majority of those centers more than 20 in the U.S. and the remainder in the UK and rest of Europe. So yes, all of those centers. It obviously active and bring contracting processes et cetera, as you would expect.

And so in order to complete this study at the last probably the last sorry go ahead the pipe their housing patient. The answer is no you can't a this is a rapidly developing disease.

Christian Martin Itin: And so in order to complete this study... Sorry, the last question is about the warehousing patient. The answer is no, you can't.

Patients are in need of therapy, and do you have to treat you can't just park those patients with some intermediary type of therapy, it's very hard to do.

Christian Martin Itin: I mean, you may say goodbye, you know, within a two, three weeks' period sort of thing, but you can't actually park patients for much longer than that. And so, Kristen, your assumptions then for completing this trial, 1H21? Obviously, you have to have data on all 70, complete response rate data on all 70 patients, but what degree of follow-up are you going to need in order to declare the trial completed or to register at all? So the primary endpoint is CR8, and CR8 is determined typically after one month. So that is a very early time point in terms of the determination of where you're tracking with the trial. It also will give you most of the safety at that point already. There's just very few safety events that happen actually after one month.

Yes, I mean, you made by you know within a two three weeks periods sort of thing, but you can you can't actually part patients for much longer than that.

And so Chris near assumptions and for completing this trial, one h. twin Tiv lawn.

What I.

Obviously, you have to have data on old 70 complete response response rate data on all 70 patients what degree follow up are you going to need.

In order to.

Declare the trial has been completed school for registration at least.

So the primary endpoint DCR eight of the CR age is determined typically after one month. So that is a very early time point in terms of the determination where are you tracking with the trial. It also will give you most of the safety at that point already knows there's very little safety events that happened actually after one month and then you all the.

Christian Martin Itin: And then you obviously want to see approximately six months of follow-up in these patients to get a good sense of what event-free survival looks like. And so that is sort of the data point that we're looking at. But as you enroll the patients, obviously, you'll have a range of follow-up for these patients, and we expect to discuss with the agency how we would actually file, what process we would file the particular trial. Are you going to allow bridging therapy in this trial? In general, and this is ALL now, adult ALL, often in adult ALL, there can be some form of bridging therapy that is being used to manage the patient. But that is sort of truly up to the treating physicians to determine what is appropriate to do with the patient.

He wants to see approximately six months a follow up in these patients to get a good sense, what the rent free survival looks like and so that is sort of the data point that we're looking at.

But actually enrolled patients obviously, you'll have a range of follow up in these and these patients that we expect to.

Discussed with the agency on how we would actually finally, what process, we would fall to the particular trial.

Right. Okay, and then are you, allowing going to allow bridging therapy in this trial.

In general.

This is a level that would all day long Oh Oh.

Often in adult MLL that that can be some form of bridging therapy that is being used to manage to the patients.

But that is sorted out is truly opt to the treating physicians to determine.

What what is appropriate to do with the patient and Theres, obviously a range of off.

Christian Martin Itin: And there's obviously a range of therapeutic options that can be used, typically some form of chemo. Unfortunately, obviously, with these patients, chemo doesn't really allow you to actually get to any responses anymore. But it might allow you to sort of just buy a bit of time or keep the disease for a little bit during the manufacturing process. And just remind me, Christian, for the U.S., will this product be manufactured in the U.S. or in the U.K.? and in the UK.

Therapeutic options at the that kind of use typically some form of chemo. Unfortunately, obviously with these patients to keep month isn't really a allow you to actually get to any responses in this setting left anymore, but it might allow you to sort of just by a bit of time or keep the disease burden.

During the manufacturing process.

And just remind me Christian for the U.S. school product being manufactured in the U.S. So we're in the UK anyway.

Christian Martin Itin: Okay, great. Thank you very much. Okay, thanks, Nick. Much appreciated. And I'm not showing any further questions. All right, well, we'd like to thank you all for joining us this morning. Looking forward to, obviously, keeping you updated and seeing you on the road.

Okay, great. Thank you very much.

Okay. Thanks very much appreciate it.

No I'm not showing any further Christmas this time.

All right well, we'd like to thank you all for joining US. This morning, I'm looking forward to obviously keep you updated and sitting on the road. Thanks, a lot of a great day.

Operator: Thanks a lot. Have a great day. Ladies and gentlemen, this does conclude today's presentation. You may now disconnect. Have a wonderful day. Thank you.

Ladies and gentlemen. This concludes todays presentation you may now disconnect have a wonderful day.

[noise].

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