Good day, ladies and gentlemen, and welcome to the Autolus Therapeutics First Quarter 2019 Financial Results Conference Call. [Operator Instructions]. I would now like to introduce your host for today's conference, Silvia Taylor, Vice President of Corporate Affairs and Communication. Ma'am, please proceed.

Thank you, Lauren. Good morning, and good afternoon, everyone. Thank you for taking part in today's call. With me today, I have Dr. Christian Itin, Chairman and Chief Executive Officer; and Andrew Oakley, Chief Financial Officer. Also, Christopher Vann, Chief Operating Officer, will join us for the Q&A portion of our call. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements, other than statements of historical fact contained in this presentation are forward-looking statements. Our actual results, performance or achievements may be materially different from those expressed or implied by the forward-looking statements. 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 November 23, 2018, as well as discussions of potential risks, uncertainties and other important factors in our other periodic filings with the U.S. Securities and Exchange Commission. 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. On Slide 3, you will see the agenda for today, which is as follows: Christian will begin by providing a brief corporate overview and introduction, followed by our operational highlights of the first quarter 2019. Andrew will discuss the company's financial results, and then Christian will conclude with upcoming milestones and news flow. We welcome your questions following our remarks. With that, I'll now turn the call over to Christian.

Thank you, Silvia. And good morning to all of you, and thank you for joining us. I'm pleased to review our progress in the first quarter of 2019 as well as some recent company highlights. Slide 5 has a snapshot of our pipeline. Each of our product candidates addresses a key issue in the development of advanced program T cell therapies. The insight that cancer cells have an inherent ability to fend off T cells using a broad range of defend strategies and mechanisms led to the development of our programs, which I'd like to quickly review before we get into our operational highlights. AUTO1 is a program designed to maintain high antitumor activity with without inducing severe cytokine release syndrome. AUTO3 aims to reduce relapse due to loss of antigen, and in combination with pembrolizumab also addresses inhibition by checkpoint. AUTO3 NG, AUTO6 NG and AUTO7 expand the capability of T cells to withstand hostile defense mechanisms by including programming modules that render the T cells insensitive to the family of checkpoints and to tumor environmental factors. Finally, AUTO4 and 5 represent a completely new approach to tackle T cell lymphoma. Now I'd like to turn to our Q1 operational highlights. Turning to Slide 7. Let's start with AUTO1 and the ALLCAR19 trial in adult ALL. Relapsed refectory B cell acute lymphoblastic leukemia in adult patients is an area of significant unmet clinical need. While most patients respond to initial combination chemotherapy regimens, once relapsed, standard chemotherapy regimens can induce a complete remission in about 10% to maximally 30% of adults with very limited durability unless patients receive a stem cell transplant. The average duration of survival is 5 to 6 months, and less than 5% of adult patients survive 5 years after relapse. The standard of care for…

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the 3-month period January to March of 2019. Slide 14. Net total operating expenses for the 3 months ended March 31 were $30.2 million, net of grant income of $2 million. This compares to net operating expenses of $15.5 million, net grant income of $0.4 million for the same period in 2018. The increase in expenses was due in general to the increase in clinical trial activity; expansion of facilities to accommodate the operational growth we have seen, including manufacturing with the our clinical trial manufacturing site, Catapult, in the U.K. coming on line; increased headcount; and the cost of being a public company. Research and development expenses increased to $22.6 million for the 3 months ended March 31, 2019, from $11.6 million for the 3 months ended March 31, 2018. Cash costs, which exclude depreciation as well as share-based compensation, increased to $17.5 million from $10.6 million. The increase in research and development cash costs of $6.9 million consisted primarily of an increase of compensation-related costs of $5.6 million primarily due to an increase in headcount to support the advancement of our product candidates in clinical development; an increase of $2.7 million in facilities costs supporting the expansion of our research and translational science capability and investment in manufacturing facilities and equipment; and an increase of $0.8 million in research and development program expenses related to the activities necessary to prepare, activate and monitor clinical trial programs. This was offset by a decrease of $1.9 million, which relates to a license fee paid to University College London in the 3-month period ending March 31, 2019. General and administrative expenses increased to $9.5 million for the 3 months ended March 31,…

All right. Thanks, Andrew. Let me conclude this part of the management discussion with a review of upcoming milestones. As I mentioned earlier, 2019 is a key year for us for multiple clinical milestones and opportunities for value-creation. As seen in our news flow chart on Slide 17, we expect to report data on our active clinical programs at key medical conferences in the second half of 2019 and first quarter of 2020. Next presentations for AUTO3 and DLBCL is planned for ESMO in September 2019. At ASH, we're planning for presentations for AUTO3 and DLBCL and pediatric ALL, AUTO1 in adult ALL and pediatric ALL and AUTO2 in multiple myeloma. First clinical data on AUTO4 is planned for Q1 at the T-cell Lymphoma Forum meeting. Additionally, over the next 12 months, we expect to move two programs into registrational trials and to progress our next-generation programs into the clinic. In conclusion and consistent with our strategy, our 2019 priorities are focused on progressing our pipeline, including moving 2 programs towards registration trials; continue to innovate and develop our product pipeline using a modular approach to T cell programming; continuing to build manufacturing facilities and capabilities; and continuing to build our organization, including establishing a focused, commercially ready infrastructure. We would now like to take your questions. Operator, please open the line.

[Operator Instructions]. And our first question comes from Biren Amin with Jefferies.

Maybe if I could start on AUTO3 question and the DLBCL program, what's the timing in terms of starting a pivotal registration study there? How much data you would need in terms of patient follow-up before you make a decision to move forward with the pivotal?

Yes. On the DLBCL side, I think we want to see a good level of CR rates, as we have discussed in the past, and also see that this is a CR rate that's [indiscernible] to three months plus period to give us a good sense for the longer-term outcome of these patients. We believe that is actually a very good surrogate for this population. When we look at the timing of that data maturation, we expect that data to mature in second half of this year, which gives us an ability to sort of move towards a registration trial towards the end of the year or early next year.

Got it. And then maybe just on AUTO6, I know this is a program -- at least Phase I was run through Cancer Research of U.K. Are there -- is there any additional follow-up from that trial that we should expect?

AUTO6 on the academic side is pretty much done, with CR U.K., and the key focus really is on the next-gen program and get that back into the clinic with the additional programming modules to improve persistence and also help address the defense mechanisms at play in neuroblastoma.

Our next question comes from Matt Phipps with William Blair.

Just focus on the manufacturing side. So at the Catapult center, congrats on getting that up and running. What is your current monthly capacity there? And are all 4 products being manufactured there, clinical products?

Obviously, what we announced is that we manufacture as of March at the facility. What that requires us to do is, obviously, gradually moving the programs into the facility, completing the tech transfer and, obviously, ramp up the capacity. We're in the midst of doing that, and we expect to sort of reach a proper level of capacity by midyear. But that's the ramp up that we're running through.

Got it. And with AUTO1, you do now have some experience and I realize not ton of patience, but treating them both by open and close process. Do you see any advantages with the priority system? There's been some academics that have reported maybe kind of more naïve or memory-like self-phenotypes. Are there any reductions in kind of product variability with the closed priority system?

Well, first of all, I mean, the open manufacturing process is, obviously, highly susceptible to sort of the operator's competence and capability. And obviously, the better trained your operator is, the more consistent the product is that you can actually manufacture. But that also highlights the challenge because it really is operator dependent. When you, obviously, manufacture on a system that is semiautomated, you obviously reduce the handling steps, you reduce the impact of the operators. And with that, obviously, it is easier to get a higher-consistency product out of it. I think if you have a highly skilled operator manually versus any process that is semiautomated, you're probably going to generate very comparable data sets. The problem is to do this consistently, and it is no doubt a lot simpler to do that on a semiautomated system. But the fundamental biology, obviously, is the same that you're dealing with, and so it's all about adhering to the protocol and managing the cells appropriately.

Right. And then at this point, can you comment on how much of an additional patient number we'll see with AUTO3 at ESMO?

So we're in -- obviously, what we had discussed is that we're, obviously, in dose escalation. We're running up, and we've initiated, obviously, the 150 million dose. We moved up from there to the next dose level as well. So we will expect a good additional number of patients there. We're not guiding on precise numbers at this point.

Our next question comes from Graig Suvannavejh with Goldman Sachs.

Let me say my congrats on the progress in the quarter. I've got one question for Christian and one question for Andrew. Christian, so in the quarter, we continue to see the competitive dynamics heat up in the CAR T space. And obviously, we saw publication of Bluebird's BB 2021 and then New England Journal of Medicine with their data there, and then also [indiscernible] did their serious refinancing with Novartis being a significant investor, and I think they're supposed to start dosing their Phase II registrational study sometime in the first half with their BCMA. So I'm just trying to get your high-level thoughts on how the competitive landscape is evolving and how you see Autolus being able to compete effectively. And the second part of that just has to do more so with how you think the multiple myeloma space will develop? And then my question for Andrew. Andrew, with 1 quarter kind of behind the company and the financial results that you announced, just trying to get a sense of whether you think that as we look at the next following quarters, whether the first quarter is reflective of what we should expect from a run rate perspective. If there is lumpiness in the quarters? Or whether there should be some gradual, steady increase as we approach the end of the year?

All right. So the question that you're asking is related to the multiple myeloma space and the program AUTO2 that we're running. We already spent quite a bit of time at the R&D event discussing the space as well, so let me briefly summarize the way we think about the space and we think about the programs and the progression. So when we look at the space, we see that we have at least 10 programs that are showing clinical data or have shown clinical data. There's probably another 30 programs that are actually starting clinical trials or close to between T cells engagers and the CAR T approaches all targeting BCMA. What is remarkable when you look at the data sets that are so far available on the clinical side is that the data looks reasonably superimposable irrespective of the program, irrespective of the modality, whether it's a CAR T or whether it's also a T cell engager. And fundamentally, what we see with all of them is a limited durability of effect for the cell products, limited persistence, and none of the products addresses the complex microenvironment that is well described for multiple myeloma. So what we're seeing with all of these products is a very similar outcome. We don't believe that any of these programs at this point has a transformational activity or transformational capability, and that includes also the programs you mentioned. So what we had discussed at the R&D day is that we believe that we have to go beyond what that current profile is. And that current profile is not limited by antigen escape, which is what AUTO2 has been designed for, but it's really limited by a persistence that needs to be extended by improving the depth of the response as well as addressing the microenvironment. And that's really what the next generation program is designed to address, and that is a key focus for us going forward as we move the program in multiple myeloma. But that's sort of what way -- the way we look at the space. So a significant change in terms of the competitive environment. I think I started talking to pretty much all investors as well as publicly about the fact that there is quite a shift in space probably now for 9 months. And what we're seeing is that the -- we need to sort of get to an improved profile to get to transformational activity. Buying a limited amount of time for multiple myeloma patients that often die of other causes than their cancer is one of the key things that we sort of need to address. So with that, I'd like to hand over to Andrew.

Thanks for the question. I mean, look, I think we're still a little bit early to say whether there's seasonal patterns or lumpiness in OpEx. I think if you look at the quarterly pattern, we've announced a fair bit of activity that'll happen in the second half of the year. So you would expect that on a quarter-to-quarter basis, you'll see increase in quarterly burn as we move through the year.

[Operator Instructions]. Our next question comes from Jim Birchenough with Wells Fargo.

It's Nick [ph] on for Jim this morning. Just going back to ALEXANDER. As you presented, I think, at the ASH meeting, you had two patients in CR, 1 at 3 months, 1 at 6 months. I think the last patient dose was nonevaluable. So can you provide us an update on that last patients and whether those 2 patients who were in CR are still in CR?

So we haven't actually -- we haven't updated the data so far, and what we would like to do is, obviously, give the full data set with the extended also cohorts that we're planning to do for ESMO. Overall, we see that data is consistent and continues to progress very positively. I think this is what we're comfortable saying at this point in time, but we're not going to comment on individual patients.

Sure. Okay. And then for ALL for the AUTO1, do you plan to continue using the split dosing? Because I think at the -- or maybe I'm getting confused between AUTO1 and AUTO3 to date. The data you had at AACR used a split dosing where they received, I think, it was 10% of the dose as a sort of teaser dose and you had some patients who had remarkable CRs just from the -- that little test dose. As you go forward in ALL, is split dosing something that you'll continue to do?

I think everyone who's been working in ALL, and this goes also back to the work I've done in the past with blinatumomab, uses actually split dosing approach, and that is really to address the high variability of tumor load that these patients can present with. So you have patients that have just relatively few cells just basically scratching the relapse stage, which is 5% or even less than cells in the marrow that are tumor cells. But you can also have patients that are up to in the 90s percent range of all cells -- almost all cells in the marrow being tumor cells. And those particular patients that have that high level of tumor load, obviously, the risk is that when you go in with a high number of T cells you get an enormously fast clearance of tumor, and that actually drives a lot of adverse events and is, in fact, not beneficial to the patient. And so what we have shown and others had shown in the past as well is that you can actually clear that with a lower number of cells, and that actually improves both the safety profile and the tolerability for patients that have these very high levels of tumor load. So yes, going forward, we will continue to use split dose. We're currently looking to potentially somewhat simplifying the schedule, but a split dose approach is a sensible thing to sort of manage a disease setting that is immediately available to the therapy. So once you fuse the cells, most of the cells actually home directly to the marrow, and that gives you almost a kick start. And if you then have a very high number of readily available target cells, you start to actually show clearance of tumor that is very, very high. You can also get into tumor lysis syndrome and those types of affects. So yes, this will continue as it actually has been done with every other program in ALL previously.

Okay. And then last question for me. As you come to the next-generation programs, can you talk a little bit about what criteria you're looking for in terms of how much better do the NG versions have to be than the non-NG versions? And what should we expect to see you talk about those?

Right. So obviously, what we look to do is we look to improve over the current versions of the programs. And the key first observation is what is that bar that we're setting with our current programs. And I think with programs like AUTO1, we have already very good sense of where that bar lies. With AUTO3 and DLBCL, we'll give, obviously, I think a first good sense planned for ESMO where that bar is. And then, obviously, we'll need, obviously, also follow-up information to understand if there are relapses, what they're driven by. And I think that sort of will, sort of, give you a sense for the improvement you can do over and above the initial therapy that we're putting forward. Clearly, in the space for AUTO2 in the multiple myeloma space we believe there is, in general, a significant opportunity to improve. When we look into the DLBCL space, again, if you look at the current programs that are there, there's a lot of room for improvement. We'll, obviously, demonstrate where we're going to get to wit hAUTO3 alone, but we also believe there is, as we go forward with these programs, opportunity to continue to move up and do that in a life cycle type of format as we progress these programs. So it's really programmed.

Do you think you can do that in preclinical models? Or is that really a question you have to address in the clinic?

I think most of the questions, the relevant questions, you will actually have to address in a smaller clinical trial to establish your initial level of activity, and then based on that activity observed, you can then make a decision whether or not the program will be taken forward. It's differentiated to the prior version or whether it's not differentiated? At which point you would not take it forward. So it's driven off a small set of clinical data to confirm the activity. Nonclinical data is not going to be predictive enough.

And I'm not showing any further questions at this time. I'd now like to turn the call back to Mr. Christian Itin for any closing remarks.

All right. Well, thank you all for joining us this morning, and afternoon, depending where you are. We hope to see you at, obviously, the upcoming scientific and investor conferences. And wishing you all a good day. Thanks a lot. Bye-bye.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program, and you all may disconnect. Everyone, have a great day.