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..

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 relapsed refractory patients include blinatumomab, a CD19-targeted redirected T cell therapy.

Blinatumomab has a 42% complete response rate but only modest durability of response as an event-free survival is only 31% at 6 months. Exploratory clinical trials with standard CD19 CAR T cell therapies in adult ALL, while active, showed considerable levels of severe cytokine release syndrome and severe neurotoxicity.

AUTO1 has been specifically designed to address the challenges. Using a CD19 bindery in AUTO1 that has an ability to drive a physiological engagement of the CAR T cell with cancer cells and avoids the excessive immune activation of the CAR T cells observed with conventional approaches.

Based on prior clinical studies looking at AUTO1 in pediatric patients, we believe that AUTO1's design might not only prevent high-grade CRS but also supports long-term persistence of the CAR T therapy. At the American Association for Cancer Research, or AACR, Annual Meeting in Atlanta last month, Dr.

Claire Roddie from the Cancer Institute of University College London presented initial data from the ongoing Phase I/II ALLCAR19 trial of AUTO1 in adult ALL patients.

As of the data cut off March 18, 2019, in the trial, 13 patients were leukapheresed, and products for 12 patients were manufactured, including 7 with Autolus’ semiautomated, fully enclosed manufacturing process.

With regards to safety, using the Lee criteria, there were no patients with severe CRS, which is a cytokine release syndrome with Grade 3 or higher, and 2 of 10 patients had Grade 2 CRS and also received tocilizumab to manage the CRS. None of the patients were admitted to intensive care due to CRS.

One patient developed delayed Grade 3 neurotoxicity following high-grade -- high levels of CAR T expansion, which was quickly reversed with steroids. Four patients died while enrolled in the trial due to progression of leukemia and due to sepsis, a common complication of advanced ALL.

Nine patients were evaluable for response at 1 month, and 8 of those 9 patients or 88% had achieved a molecular complete response. One patient died of sepsis before the 1 month evaluation point. On Slide 8, we would like to provide some context on how this data fits into the landscape of ALL therapy.

First, we would like to highlight the consistency between the pediatric and adult data sets for AUTO1. Both data sets show a higher than 80% molecular complete remission rate without inducing Grade 3 or higher cytokine release syndrome by Lee criteria.

Encouragingly, the 12 months' event-free survival for the pediatric patients was 46%, and overall survival at 12 months was 63%. Finally, persistence for the CAR T cells in children was excellent. The most recently approved products for the treatment of adult patients in -- with ALL are blinatumomab targeting CD19 and inotuzumab targeting CD22.

Blinatumomab is, like the CAR T therapies, a redirected T cell therapy that is fully approved across all age groups of ALL. The CR rate is 42% with a molecular response rate of 28% and with an event-free survival at 6 months of at 31%. Blinatumomab was approved as a breakthrough by the FDA in 2014.

While Kymriah, a CD19-targeting CAR T therapy was approved in pediatric patients in 2018, no CAR T therapy has been approved for adult ALL patients to date.

The key challenges have been the high level of high-grade cytokine release syndrome, as seen with Kymriah in children, and a high level of high-grade neurotoxicity observed with just CAR T and other programs in adult patients with ALL.

Our initial data for AUTO1, both in children and in adults, shows a lack of high-grade CRS by Lee criteria with no patients treated in ICU for high-grade CRS. Also the high level of high-grade neurotoxicity appears -- observed with other programs appears low and is at similar levels to blinatumomab.

However, the activity level is very high with more than 80% of the evaluable patients achieving a molecular CR. In summary, we believe that the strong persistence of the CAR T cells over time, coupled with a low frequency of severe CRS events seen in these patients, represent encouraging initial data for AUTO1 and relapsed refractory adult ALL.

Of note, we expect AUTO1 in adult ALL to move into a registration trial towards the end of this year. Moving on to AUTO3 in pediatric ALL and to Slide 9. In the quarter, we provide an update from the ongoing AMELIA Phase I/II study in pediatric ALL.

These data demonstrated that 6 out of 6 patients treated at highest dose level of 3 million cells achieved -- or achieved minimal residual disease, negative complete responses. Ongoing MRD negative CR remissions were noted in 4 out of 6 patients with duration up to 10 months as of February 2019, the date of the latest follow-up.

There have been no reported CD19 or CD22 negative relapses in CAR T-naive patients. Data also showed that AUTO3 continues to be generally well tolerated with no high-grade CRS, no ICU admissions and no pressers or critical care support for CRS required. The Phase II portion of this study is expected to start in the second half of 2019.

We're also pleased to receive the recent news that the United States FDA has granted orphan drug designation to AUTO3 for the treatment of acute lymphoblastic leukemia.

Moving on to our inaugural research and development day on March 26, 2019, which we hosted in New York and allowed us a unique opportunity to present an in-depth overview of our differentiated technology, multiple programs, market opportunities and the significant pipeline progress we have achieved to date.

A major focus of the R&D Day was on how to address tumor heterogeneity using our modular approach to T cell programming, as illustrated on Slide 10. The key focus of the presentation was encountering immune modulation employed by the cancer cells, in particular checkpoint-based inhibition and TGF-beta-mediated dia-modulation of T cell activity.

An example of modular programming is shown on Slide 11. We have planned to introduce these auxiliary programming modules into next-generation programs for AUTO2, AUTO3 and AUTO6. Going forward, as starting with AUTO7, in prostate cancer and other development programs, we will include 1 or more of these programming modules from the onset.

We believe our ability to rapidly iterate programs enable us to drive a high pace of innovation, and in particular, in solid tumors, will allow us to penetrate the defense mechanisms. Finally, moving to Slide 12. Important to our ability to serve patients is product manufacturing and delivery.

Our facility at the gene and cell therapy Catapult facility in Stevenage U.K. is critical for clinical trial supply. The facility and our suite are now operational and started manufacturing products for clinical studies in March 2019. In January 2019, we initiated a build-out of a commercial manufacturing facility in Enfield in the U.K. called the GRiD.

This facility will provide global supply for viral vector as well as planned capacity for up to 1,000 T cell therapies annually. The GRiD is planned to serve as our initial commercial launch facility.

Also in 2019, we signed a long-term, full building lease for a built-to-suit facility that will be the site of our first full commercial-scale manufacturing center with a plant capacity of up to 5,000 T cell therapies annually. This facility will also house our new U.S.

headquarters and will be located in Rockville, Maryland, close to our current offices. The facility is expected to open in 2021. With that, I will turn the call over to Andrew for our first quarter 2019 financial update.

Andrew?.

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, 2019, $4.3 million for the 3 months ended March 31, 2018.

Cash costs, which, as I mentioned, excludes depreciation as well as share-based compensation, increased to $6.3 million from $3.5 million.

The increase of $2.8 million consisted primarily of an increase in compensation-related expense of $1.2 million due to the -- due to an overall increase in headcount and an increase in legal and professional fees of $0.9 million related to insurance, patent costs, communications costs; an increase of $300,000 in preliminary commercial costs; and an increase of $300,000 as well in facility costs.

The net loss attributable to ordinary shareholders was $27.2 million for the 3 months ended March 31, 2019, and that compared to a loss of $16.7 million for the same period in 2018.

And the basic and diluted net loss per ordinary share for the three months ended March 31, 2019, totaled $0.69 per share compared to a basic and diluted net loss per ordinary share of $0.58 for the 3 months ended March 31, 2018. On April 15, we announced the closing of an underwritten public offering in the U.S.

of American depository shares, or ADSs, which represented 4.83 million ordinary shares at a public offering price of $24 per ADS, which includes an additional 630,000 ADSs issued upon the exercise in full of the underwriters' option to purchase additional ADSs.

Aggregate net proceeds to Autolus after underwriting discounts but before estimated [Technical Difficulty] were $109 million. All of the ADSs were offered by Autolus. Cash and cash equivalents at 31 March, 2019, totaled $187.7 million, and that compared with $217.5 million at the end of December 31, 2018.

Obviously, the proceeds from the public offering in April are not included in these numbers. We anticipate, therefore, that cash on hand would provide us a runway into the second half of 2021. And with that, thank you very much. And I'll now hand the call back to Christian to give you a brief overlook of our expected upcoming milestones.

Christian?.

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..