Autolus Therapeutics (NASDAQ:AUTL) Q2 2020 Earnings Call

0:00 Hello ladies and gentlemen and welcome to the otolith therapeutic second quarter 2020 financial results conference call as a reminder this conference call is being recorded i would now like to turn the conference over to your host dr lucinda crabtree vice president investor relations please go ahead thank you crystal 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 second quarter of 2020

0:30 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 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 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 March 3, 2020 as amended, as well as discussions of potential risks and uncertainties and other important factors in our other periodic filings with the SEC.

1:29 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 three, agenda, you'll 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 second quarter of 2020. 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.

2:20 All right. Well, thank you very much, Lucinda.

2:21 This is probably the most thorough, all forward looking statements that I think we had. So with that, good morning to everyone and thank you for joining us. I'm pleased to review our progress for the second quarter 2020. First on slide five, I would like to update you on the current and potential future impact of the COVID-19 pandemic on our business. At our last financial update call in May, we were at the height of the first peak of the COVID-19 infection in the New York City metropolitan area. the UK and Spain. For some weeks, patients could not be enrolled into clinical trials in those areas. In contrast, sites in the south of the US continue to operate normally during that period and continue to enroll Auto 3 patients. In parallel, the startup of our Auto 1 Pi Pivotal study in Q2 has been progressing to plan.

3:13 While we're now in a more stable situation in the first hit areas and patient enrollment resumed, We are monitoring with some concern the developments in the South and the West of the US. While we continue to enroll patients in those areas, we're closely monitoring the situation. Our key focus is on patient safety and ensuring data integrity in our trials. Most of our suppliers have been coping well through the first stretch of the pandemic, while some have experienced issues. We are working closely with all our suppliers to ensure uninterrupted supply of essential goods and services for our operations. Finally, We've been working closely with our logistics partners to ensure uninterrupted and timely continental and transatlantic deliveries of leukophoresis and final products.

4:00 To date, our lead programs, order one and order three, have not been significantly impacted by the COVID-19 outbreak. However, depending on the development of the pandemic in the second half of 2020 and into 2021, our trials could become impacted. For auto four, we experienced delay in patient involvement for our ongoing phase one clinical trial. This trial is conducted in the UK and in Spain, and the healthcare systems in both countries have been heavily impacted, leading to a stop of involvement in the second quarter. The return to normal activity in both countries has been slower than expected, and we now expect first data from this phase one study to be available in the first half of 2021 instead of the fourth quarter of 2020. With respect to our preclinical programs, these have been minimally impacted and we continue to expect Auto 5, Auto 6NG, Auto 7 to enter the clinical development in 2021. Our first clinical studies with Auto 1NG in pediatric ALL and Auto 8 in multiple myeloma remain on track to begin in the second half of 2020.

5:06 But moving on to our corporate highlights and starting with our clinical programs on slide six. We've had a busy quarter across our portfolio with positive data presentations at key medical conferences. Both our later stage clinical programs, Auto 1 and Auto 3, continue to show very encouraging clinical activity with tolerable safety profiles as highlighted in two separate presentations at ASCO and EHA. We also follow both these presentations with analyst events. I will touch on these clinical updates a little later. However, focusing on the operational aspects and starting with Auto 1, We have now commenced enrollment of patients with relapsing remitting adult acute lymphoblastic leukemia in our pivotal phase 1b2 auto 1 program and we're targeting to have data by the end of 2021. With regards to our lead product candidate for the treatment of BLBCL auto 3, we have now selected the recommended phase 2 range of 450 to 450 million cells with a single dose of pembrolizumab included in preconditioning.

6:09 In addition, the company has also commenced a 20-patient outpatient cohort as an extension to its ongoing Phase I-II Alexander study, with results expected by the end of 2020. The data from this outpatient cohort will provide important insights that will be used to refine the design of the potential pivotal Phase II part of the Alexander study. Finally, we are also pleased to have been invited to present a mini-oral presentation at ESMO on September 18, 2020. where we'll give a further clinical update from the Alexander study. On that note, we plan to host an analyst event on this same day. Finally, the last item I would like to mention on this slide is other forthcoming clinical data updates expected through the second half of 2020. For order one in adult ALL, we plan to present longer-term follow-up data towards the end of 2020, likely at ASH. For order three, as I've mentioned, we would look to update with additional patients from our ongoing Alexander study as well as longer-term follow-up data at ESMO. We would also look to provide a further update by the end of 2020, again, likely at ASH, by which time we would also look to update you on the data from the outpatient cohort. Moving to slide seven.

7:23 At AACR, we updated on three of our early-stage pipeline programs, Auto 5, Auto 6MG, and an oral presentation on Auto 7. The preclinical data presented reinforced the strength of our binder discovery capabilities with our ability to selectively target two separate populations of T cells in T cell lymphoma as defined by the mutually exclusive expression of T cell receptor beta chain constant domains 1 and 2. We're excited about the profile of Auto5, our anti-TRBC2 kinetic antigen receptor, which is the complementary program to our clinical asset Auto4, which targets TRBC1 positive. In addition, we also demonstrated the utility of our broad technology toolkit whereby we showed how our modular approaches in Auto6NG and Auto7 can address the hostile solid tumor microenvironment in models of small cell lung cancer and prostate cancer respectively.

8:20 The new data suggests that Auto6NG can overcome key immune suppressive mechanisms in the tumor microenvironment. Furthermore, the Auto7 program builds on the novel and optimized CAR2-PSMA designed to be highly active even with low BSMA target expression and also in an acidic environment often characteristic for solid tumors. Auto7 then combines modules introduced in Auto6NG with a novel module leading to a low level secretion of interleukin-12 to change the prostate tumor from immunologically hostile to immunologically supportive environment. We've guided at all three programs presented at AACR, Auto5, all the six NG and all the seven are expected to enter the clinic in 2021. Moving to slide number eight.

9:11 Given the maturing of our clinical I did to announce earlier this week, Dr. Jay Backstrom's appointment to the board of directors. Jay brings a wealth of oncology development, regulatory and portfolio strategy experience to the board. Under his leadership, Celgene has developed a broad range of therapeutics, including small molecules, biologicals, and CAR-T programs in one of the industry's most significant hemato-oncology pipelines. Furthermore, we also announced Dr. Nushmiya Kokar's promotion to Senior Vice President, Clinical Development, taking over full responsibility for all our clinical development activities. Nushmiya has been instrumental in the development of our clinical programs at Otelus, and we very much look forward to her continued strong leadership.

9:57 Finally, we now instruct Dr. Vijay Pedaretigari will be leaving the company, moving with his young family back to the U.S. Over the past four years, Vijay has played a key leadership role in establishing and executing the clinical development strategy to advance our program T-cell therapies, and we do wish him well in his future endeavors. As well as the board management update, worth mentioning that we're also extending our manufacturing capacity at the Cell and Gene Therapy Catapult to secure initial commercial launch capability. Moving to slide number nine. I wanted to spend a brief moment recapping on our lead program auto-on in adult ALL. Adult ALL is a challenging disease and typically disease available to patients. A lot of these patients have significant comorbidities, making them a more fragile patient group than pediatric ALL. The indication is approximately three times the size of pediatric ALL, which represents an attractive market opportunity.

10:54 Within the US and the top five European countries, approximately 3,000 patients every year are at the end stage of their treatment, having failed chemotherapy and stem cell transplant and therefore require other options. At this point, there is no CAR T therapy approved for adult ALLs. When we created AutoOne, We designed a product that has an ability to have a very high level of anti-leukemic activity to cope with the rapid growth of leukemic cells in the bone marrow, a very long persistence to put long-term pressure on the leukemia and get to a transformational outcome, combined with a tolerable safety profile, which is particularly important for elderly patients with acute leukemia. Now turning to slide number 10, to recap on the update we provided at EHA in June on the Olkar-19 study with Auto-1.

11:46 Our data suggests that OTO-1 has a superior efficacy profile with a comparable safety profile to standard of care. The overall response rate and MRD negative CR rate was represented at EHA was 84% for all 19 patients treated in this study. Responses appear durable and notably first patients are beyond 18 months in molecular complete remission without receiving a second transplant. In fact, for all the patients treated, only two patients have been consolidated with a transplant. 11 of the 19 patients continue to be disease-free with a median follow-up of 12.2 months with the range ongoing up to 24.4 months. Putting this data in context with some of the other standard of care therapies that are available, the overall response rate we see is approximately double that of Blinitumab and looking at the event-free survival or median PFS, this also compares very favorably to Blinitumab or Inutuzumab where approximately half the patients are consolidated with transplants. Furthermore, Auto-1 event-free survival at six months is high at 62% for all patients and 76% for patients treated with the closed manufacturing process which we're using going forward in the pivotal study.

13:02 With the absence of post CAR T consolidation with transplants, the treatment effect is that of Auto-1 as a standalone therapy. But based on this data, turning to slide 11, We have started enrollment into the pivotal program Auto 1 AL1 in adult ALL. As a reminder, the CTA was filed in the UK in Q1 and cleared earlier this year and the USID was accepted by the FDA in the second quarter. We have now sites open and running and enrolling patients. As a reminder, the study has a phase 1b run-in and the pivotal program comprises a single arm 100 patient study with relapsed refractory patients. The primary endpoint is complete remission rate Secondary endpoints include molecular CRs, event-free survival, and duration of response.

13:47 We remain on track to report full data by the end of 21. Let's now turn to slide 12, where I would like to switch gears and talk about ORO3, a program that is designed for the treatment of patients with diffuse large B-cell lymphoma. As you all know, DLBC is a much bigger indication than adult ALL and a setting where there are already two approved CAR T therapies, which is CART and CHYMRAYA, plus Liza Zell, or otherwise known as JCAR17, pending approval. We know this is a large opportunity with approximately 10,000 patients on the back end of the disease, which is a sizable population with a very significant medical need. The aim in DLD-CL is to achieve durable, complete remissions. Approved CAR-T products, Jiscart and Cambria, have a high objective response rate between 70% and 80%, but only 29% to 37% of the patients achieve durable, complete remissions. The two main drivers for relapses post-remission are loss of antigen and expression of PD-L1 on lymphoma cells.

14:48 Auto3 is designed to achieve a high level of sustained complete remissions. To counteract loss of antigen, a validation mechanism, we engineered two chimeric antigen receptors, one targeting CD19, the other CD22, into each CAR-T cell. The rationale is that the lymphoma cell would have to lose both antigens simultaneously to avoid recognition by the CAR-T cell, a much less likely event to occur than a single antigen loss. The molecular composition of our CARs is different from any other CAR-T product, even from OTO-1, with different binders targeting the antigens, a different co-stimulatory domain for the CD19 CAR, and a novel CAR architecture for the CD22 CAR. In addition to the unique molecular design of OTO-3, we're also using Pembrolizumab during preconditioning to counteract PD-L1-mediated checkpoint inhibition. As reported at ASCO and DHA, audit 3 shows a high level of complete remissions with about 60% CRs at the recommended phase 2 dose.

15:46 Moving to slide 13, encouragingly, to date there have been no early read-ups observed from patients who achieved CRs, which bodes well for sustained high level of CRs. Larger patient numbers and more follow-up will provide further clarity towards the end of this year. Slide 14, Importantly, patients responding to Olifree therapy showed limited CAR-T related toxicities supporting treatment of patients outside of academic centers and also in outpatient setting. This is particularly important in DLD-CL as 80% of third-line patients are treated outside academic centers in the US. Currently approved products are only tapping into significantly less than 20% of the market which is managed by the academic centers.

16:32 There's very little to no penetration of the remaining 80% of the market, which comprise settings that cannot deal with the intensity of management required for the current tea products. We believe this creates a highly attractive opportunity for the profile of product that we're seeing with order three. As I've mentioned, we expect to provide an update on patients treated in our outpatient extension cohort by the end of 2020. So let's turn to slide 15. As we have discussed, we've developed the first in-class CD19 and CD22 CAR with novel signaling domains designed to provide best-in-class efficacy with high rates of durable complete responses. Given the differentiated clinical and safety profile we have reported on so far, we see a really attractive opportunity for Auto3 as an outpatient solution for patients with DRBCL, therefore maximizing the commercial potential of a CAR-T product across all settings of care.

17:28 Finally, on slide 16, I wanted to remind you of the broad and exciting next generation pipeline we're proud to be developing at Otolus. Otol1 NG, our next generation program in ALL, retains the fast off-rate CD19 CAR we use in Otol1 and adds a CD22 CAR, a novel one. We will look to progress this program into phase one clinical study in the pediatric setting in the second half of this year. CD19 negative relapse appears to be a greater issue in pediatric patients compared to adult patients with ALL and hints the focus with this program first in pediatric patients. Auto 3NG is a life cycle management program in DLBCL and is representative of the ongoing innovation at Autolus. I also wanted to mention Auto 8 which is our next generation program multiple myeloma due to enter the clinic in second half of 2020 as well.

18:23 Lastly, The suite of next generation programs is showcased at AACR a few weeks ago. We will look to move into the clinic in 2021, including our first solitary programs for both prostate cancer and small cell lung cancer, which we're excited to be progressing. With that, I will turn over to Andrew for the second call 2020 financial update. Andrew.

18:51 Thanks, Christian, and good morning or good afternoon to everyone. If we move to the next slide, it's my pleasure to review our financial results for the second quarter. That's for June 30, 2020. Starting with our cash position, cash and cash equivalents at the 30th of June totaled $212 million and that compared with $243 million at the end of the previous quarter. Net total operating expenses for the three months ended 30th of June 2020 were $39.5 million. That's net grant income of $0.3 million. And that compared to net operating expenses of $37.2 million net grant income of the same amount for the same period in 2019.

19:43 Research and development expenses increased to $31.3 million for the three months ended 30th of June. from $26.2 million for the three months ended 30 June 2019. Cash costs which exclude depreciation and amortization as well as share based compensation increased to $26.5 million from $20.2 million. The increase in research and development cash costs of $6.3 million consisted primarily of one An increase in compensation and employment related costs that's net though of lower travel costs as a result of the ongoing pandemic of $1.8 million and that's due to an increase in employee headcount to support the advancement of our product candidates in clinical development.

20:29 Secondly, an increase of $3 million in project expenses as a consequence of the advancement of our clinical portfolio which includes all of the research process development manufacturing activities necessary to prepare, activate and monitor the clinical trial programs. Thirdly, an increase of $1.3 million in facility costs related to the commencement of the LEAF for an additional manufacturing suite and the continued scaling of operations in the manufacturing facility and lastly an increase in IT and telecoms general office expense and professional fees of $0.6 million which is offset by a decrease in materials purchases of $400,000. Non-cash costs decreased to $4.8 million for the three months ending 30th of June from $6 million for the three months ended 30th of June 2019.

21:26 This decrease is primarily related to share-based compensation expenses included in research and development expenses which decreased by $1.3 million as a result of a lower fair value of stock options recognised in the period and this was offset by a small increase in depreciation. General and administrative expenses decreased to $8.5 million for the three months ended 30th of June 2020 from $11.4 million for the three months ending 30th of June 2019. Cash costs, which as I've explained exclude depreciation as well as share based expense compensation, decreased to $6.7 million from $7.3 million for the previous corresponding quarter last year.

22:15 Compensation-related expenses decreased by $100,000, aided by lower travel costs as described above. Further, there was a decrease of $0.7 million in commercial activities, and these decreases were offset by a marginal increase in legal and professional fees of $100,000. Non-cash costs decreased to $1.8 million for the three months ended 30 June 2020, from $3.9 million for the three months ended The decrease is attributed to share-based compensation expense as a result of the lower fair value of stock options being recognized during the period. Interest income decreased by $1.1 million for the three months due to lower interest rates. Other income decreased to $0.5 million for the three months end of 30 June 2020 from other income of $4.4 million for three months primarily related to a decrease of the exchange rate between the UK and the pound for the three months ending 30th of June 2020 as compared to the three months ending 30th of June 2019. Income tax benefit increased to seven million dollars for the three months ending 30th of June 2020 from 3.3 million dollars for the corresponding period last year and that's due to increased R&D expenses which led to an effective and more. Research and development credits are obtained at a maximum

23:47 rate of 33.35% for our qualifying research and development expenses and the increase in the net credit was primarily attributable to an increase in that eligible expense. So overall net loss attributable to ordinary shareholders was $32 million for the three months ending 30th of June 2020 and that compared to $28.5 million for the corresponding period last year and this resulted in a basic and diluted net loss per ordinary share for the three months ending 30th of June of 62 cents compared to a basic and diluted net loss per ordinary share for the corresponding period last year of 65 cents and consistent with the previous guidance the company anticipates the cash on hand provides us with a runway into 2022.

24:41 And with that, I'll now hand the call back to Christian to give you a brief outlook on

24:46 expected milestones. Christian. Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones at new slow through 2020. Let's move to slide 20. The upcoming six months will yet be another eventful period for us with multiple clinical milestones and opportunities for value creation. Our chief and most imminent operational focus will be continuing enrollment and dosing of patients in the Pivotal Phase 1 E2 trial for Auto 1 in adult ALL and completing the outpatient cohort for Auto 3 in DLDCL. We also expect to report clinical data on the Auto 3 Alexander trial at the forthcoming ESMO meeting and a further update plan for ASH and updated Auto 1 Olcar 19 data also planned for ASH. In the second half of 2020, we'll look to progress Auto-1 and G, our next generation program for ALL into phase one clinical study in the pediatric setting.

25:37 And in the same period, we also expect our next generation multiple myeloma program Auto-A to enter the clinic. Towards the end of the year, we expect to progress our first allogeneic program into clinical development as well. As we move through to the end of the year and into next year, we will look to progress a number of other preclinical candidates to point to phase one readiness including Auto5, Auto6MG and Auto7 which are the programs we updated you on at ACR. We plan for these programs to enter into the clinic in 2021. Finally, in the first half of 2021, we look forward to providing an interim update on Auto4 and T cell lymphoma and we expect to present on a small number of additional patients. In conclusion on slide 21, I'd like to recap the major messages from today's call.

26:25 Auto1, our first pivotal program, has started in Q2 as planned. Given the positive safety and efficacy profile today, we believe that Auto1 has the potential to be a best-in-class CD19 CAR-T program in adult ALL, a disease setting with very high unmet need. Second, Auto3 and DODCL will have additional clinical data updates at ESMO and possibly ASH. In Q2, we have initiated the outpatient cohort with planned data update on that cohort by year-end. The company is in a good position and combined with cash on hand of $212 million, we feel well poised for success. We're now happy to take questions. Operator? Thank you. The phone lines are now open for questions. To ask a question live, please press star 1 on your telephone keypad.

27:13 Once your name has been announced, you may then go ahead with your question. Our first question is from Mara Goldstein, Mizuho Securities USA.

27:29 Hello, this is Mara. Can you hear me? Yes, how are you? Hi, thanks. Sorry, thanks for taking the question. Just a couple of questions. First of all, can you provide some more color regarding the data updates expected at ESMO, such as additional patients and I had a question on auto aid and really more around the environment for patients in multiple myeloma trials given the number of cell therapy trials currently underway and the competing late line therapeutics for that disease, particularly under the umbrella of where we are now with COVID and talk a little bit about that. Sure.

28:13 With regards to the second question, I think the environment we're seeing is certainly one where there is a number of new therapeutic options that are becoming available. I think the primary focus we see with regards to the first approvals is clearly on the US and we'll expect some delay for European approvals. Our initial work will be executed in Europe and so we think that from that perspective we will not yet feel an impact from the new programs coming in. and then I'm asking if you have to repeat the first question, I'm really sorry.

28:54 Right, just regarding data updates at ESMO, would you be able to give us some additional, some color on what we can expect in terms of additional patients, durability and the like?

29:05 Thanks, Mara. Yes, so in terms of additional data updates, what we had updated at ASCO was based on a data cut obviously in early part of the Thank you very much. As we go towards ASH we expect to be able to ask the patient experience from the outpatient cohort for the patient.

29:55 If I could just ask one more question and it's on the auto free outpatient program and within the protocol defined as outpatient what I guess what would be considered success from an outpatient perspective at what point when patients are treated if they have an emergent event and end up having to go to hospital. Are they then considered an outpatient failure, if you will?

30:23 No, I mean, the key purpose of the outpatient cohort is actually to familiarize the centers with the product and gain experience with the patients in an outpatient setting, understand the handling as well as the overall management. We have to also understand that obviously the patients, particularly at the very late stage of the disease, often require actually hospitalization to manage the disease itself. So this is a lot about gaining experience, understanding the profile, understanding the management. And that is sort of what the key purpose is of the outpatient cohort and is really laying the foundation to then include patients in outpatient setting in a pivotal study as well.

31:06 All right. Thank you very much. Thanks, Mara. Our next question comes from Biren Amin from Jefferies.

31:20 Yeah, hi guys. Thanks for taking my questions. Christian, just on the outpatient cohort, are patients dosed with prophylaxis regimen of IL-6 inhibitors and or steroids?

31:35 No, the answer is no. They're not going to be managed by giving them IL-6 monoclonal or steroids for that matter. So the patient will not be managed that way. That would not be, I think, a good way to go.

31:52 And just to clarify on this outpatient cohort, will the data at the end of the year, will that inform you on its utility for use in the pivotal trial next year in the LBCL?

32:07 We believe it will and as I pointed out a lot of this is really about gaining experience and I think in that sense it's going to be important for the centers to actually gain experience in that setting and that is important to lay the foundation to include these patients as well.

32:25 And then maybe just one last question. On the Auto A program, what learnings did you take from the Auto II and apply that to the development of AutoAID.

32:39 One of the key focus that we were putting into the design of the AutoAID program is really to drive for the ability to make very deep cuts and be active at very low levels of target antigen. Both of those elements we believe are important to actually induce a profile, to create a profile that can lead to a high level of molecular remissions, which is really what we need to aim for, which are very stringent molecular remissions in that setting. So that is what the program is designed to do, and there is also additional elements that we built in that we haven't yet discussed.

33:17 Great. Thanks for taking my questions. Thanks a lot, Barron. Thank you. Our next question comes from Eric Joseph with JP Morgan.

33:30 Thanks for taking the questions. I also just had a follow-up on the outpatient cohort. And just in your comments about how to think about the data toward year-end, when you describe patient experience, can you just sort of help us with expectations in terms of sort of duration of follow-up there? Would you expect to be reporting, I think at that point, primarily safety? and maybe just an update on enrollment to date in that cohort.

34:07 Hi Eric, thanks for joining. I'm not sure whether the entire question was fully audible on the recording. I think the key question is what is the type of data we expect by year-end for order three in terms of follow-up safety, etc.? ? So I think with regards to the cohort that defined the recommended phase 2 dose, obviously that cohort has been fully involved and patients have been treated before middle of the year. And so we'll have a very good follow-up in that patient group of three months and more, which gives us a very good view in terms of not only the CR rate at one month, but also starting to get a feel for sustained CR rate.

34:52 We've already obviously had patients that we have now observed for 18 months or longer, and obviously that gives us a very good view in terms of that fatality of the CRs that we have induced, gives us a very good view over an extended period of time of how these patients are faring. And I think with that, we'll get a very good understanding of what the durable complete remission rate will look like with auto three. So I think that is a very important part of the data. The second part obviously is in a larger patient group obviously a corroboration of the overall safety profile of the product which is an important feature of Auto3 and so I think we're going to have obviously substantive addition in terms of with the additional 20 patients that we're enrolling to give us a very robust data set both on the safety overall but also from an overall CRA perspective and with regards to durability of effect obviously all the patients we've treated until now will have at least three months of follow-up and that gives us a very good view of the ability of those CRs to sustain over time.

36:11 Okay great. I guess short of seeing similar safety in the outpatient cohort. Is there really anything in terms of logistics, the ability to manage patients in the outpatient setting that would, or manage patients in the outpatient cohort that would lead you to not pursue it in a pivotal setting?

36:41 I think it is really about corroborating the data we have in this setting. and as I indicated, an ability for the centers to gain experience. You know, the current experience with CAR T is to use the CAR T is predominantly an inpatient setting. That is what all the guidelines are directed to. This is pretty much what the safety management, et cetera, is really focused on. And so it does take experience. And I think this is what the patient cohort actually allows us to start to build. I think will be important as we're looking forward in this program. but it is you know on the on the pure safety data side I think corroborating the data is important you know getting a better understanding of you know duration of adverse events and those types of information as well I think will be very helpful in understanding the overall profile and you know preparing ourselves to include those patients going forward as well.

37:38 Okay got it thanks for taking the question. Thanks a lot Eric. Thank you. Our next question is from Jim Bertineau from Wells Fargo.

37:50 Hi guys, congrats on all the progress. A few questions for me. I guess first, just on the outpatient cohort, could you remind us again what the triggers are for patients to be readmitted, you know, if they were dosed in the outpatient setting and, you know, around fever, you know, the time course of fever that would Are you seeing anything early in the outpatient cohort that's given you confidence that you've got a viable profile for that setting?

38:22 First of all, thanks for joining, Jim. Very good questions. Obviously, the current guidelines in the CAR T field and in general for late stage HDL-BCL patients is that when patients develop a fever, you want to be sure that you can exclude infectious disease. And so typically these patients do get admitted, get put on an antibiotic and then are monitored. If obviously the patients are doing well, the fever subsides quickly, the patient can be discharged quickly as well. So the timings around those will be important. And a lot of these patients do, whenever they develop fever, whether they're under therapy or not, will have to go to the hospital, get checked. for potential infections and obviously the risk of sepsis that could develop and it is really around managing that risk that I think you have to be very mindful and very focused on from a fever perspective. Now this is no different whether the patient is on CAR T or the patient is just being managed at that stage of the disease and there is no difference in terms of the rules that apply and how you actually manage those patients at that point in time. and others.

39:35 So in that regard, that is a key parameter we're looking at in terms of kind of the early experience. I think it's, you know, we don't have enough patients, I think, to have a feel how this is going to develop through the trial. You know, we have to run the cohort and get a good feel for that as we're looking at the 20 patients in totality.

39:57 And then, Chris, maybe a broader question on ability to navigate the pandemic. You referenced the southern What is your exposure to sites in those areas and is there a way to adapt the study to enroll in sites that are less hotspots?

40:18 We do have a significant number of study centers across the U.S. This allows us to focus our enrollment more towards the sites. that are less impacted and that actually has worked well so far but you know it's something you have to be very vigilant about and and you know you have to monitor very carefully and we've seen certainly in the last you know the month of July we've seen you know pretty significant and rapid surges in places like Miami or Houston that I think we all hoped you wouldn't see frankly now those centers still continue to operate the cancer center still continue to operate but it's very clear that when you listen to the public health officials that some of those places are approaching or have been approaching maximal capacity on their ICU beds, et cetera, which obviously starts them to put or present the risk where that could spill over into cancer centers as well. So that's certainly one of the things we're looking very carefully at. From a geographic distribution perspective, we're very well distributed across the US with our centers. and obviously we're also having you know centers in the UK on the auto 3 side and there is an element of an ability to balance out and you know as you can imagine while we work you know you know pretty heavily hit in New York City

41:48 in the middle of and towards the end of April we now actually have enrolled quite a few patients out of New York so it's really kind of managing as after the pandemic kind of flows frankly through the country managing accordingly and making sure we're sort of focusing on the centers that are less impacted or less likely to be impacted in a way that would actually put the patients frankly at risk. But it's going to be a topic we'll have to watch very carefully as we go through the second half of the year with the risk of having kind of a flu on top of COVID. and frankly you know people's attitudes starting to wane and you know people start to get fed up with where we are and I think that aspect is probably one of the biggest risks that we're all going to be dealing with is that we frankly keep our act together as a population and you know depending where we are we know we had I think our issues with actually doing that and that is actually I think where the fundamental biggest risk is that we're dealing with.

42:55 Just a final question, Christian, and thanks for that. Just in terms of maybe moving your cell therapies up to earlier lines and away from less, you know, more from the brittle patients in the salvage setting, can you maybe speak to that strategy to maybe move auto one or auto one NG or auto three or auto three NG up to earlier lines? What strategy is there?

43:21 I think it's a very important point. It's an area we're looking at very intently. So we're looking at ways for early lines of therapy settings for all the three in DOBCL, which we believe is important. And we're also looking at the opportunities in the ALL setting as well, where clearly we know from the experience with Blenatumumab you know going to an early line of therapy basically in that particular with that particular redirected T cell therapy doubled the molecular CR rate by going earlier in the in the setting so there's a very clear very strong rationale for moving to earlier setting and a very significant opportunity for improved outcomes at a number of levels in these patients also less beaten up they have typically the disease isn't quite as rapidly progressing as we have at the last line setting and that actually together actually gives you an opportunity to have a much more profound impact for these patients.

44:33 Great, thanks for taking the questions. Thanks a lot, Jim. Thank you. Our next question comes from Asika Goonwardeen from Truist.

44:45 Hi guys, good morning and good afternoon. Thanks for taking my question. I was wondering about auto four. Could you maybe talk to us a little bit about what you would expect in the data in the first half of 2021 and what kind of follow up? And then also, if I can add on to that, T cell lymphoma is a very diverse set of diseases. I was wondering if there's potential for you to get a broad indication across all T cell lymphomas by focusing on the three subtypes that you're looking at in the phase one study?

45:18 First of all, thanks for joining us again. The AutoIV obviously is still in dose escalation, so it's going to be a smaller number of patients with dose escalation information, and we'll see where we are at that point in time in terms of the dose levels. But the information will predominantly be on the activity of the product at certain dose levels in a small number of patients. In terms of the disease setting, you're right, T-cell lymphomas are quite heterogeneous in terms of the population. However, when you look at outcomes, the large settings actually have a very similar, rather homogeneous outcome. So you can actually include the larger settings in a single trial and actually run it as a single trial that actually has the same outlook in terms of timeline with regards to relapses duration of responses etc in general where they behave very similarly and that is what we're doing so we're actually allowing the major indications in T cell lymphoma to be recruited into the study and have an indication like PTCL as a separate entity that would actually have to be developed as a separate label.

46:39 Great, thank you. All right, thanks a lot. Thank you. Our next question comes from Robert Andrew with William Blair. Hi there. This is Robert Andrew for Matt Fibbs.

46:54 Thanks for taking our questions. Just a couple from me. I noticed in the press release here that the manufacturing capacity has been increased at the Catapult site. Is that just in general to support the Pivotal for Auto 1 and the potential launch there, or is that kind of also taking into And then I guess given the number of candidates that are entering the clinic in the next kind of six to 12 months, you know, is the capacity there now able to support all those studies without strain or does that have to be a prioritization?

47:35 Very good question. So we're adding capacity at the South therapy catapult to actually support a launch for for all to one. um supporting launch for all the three we believe will actually require more capacity and that's one of the reasons why we're obviously working on the uh on the Rockville facility that we have introduced uh you know a little while ago um with regards to the um uh capacity for the conduct of clinical studies obviously we do have uh quite a bit of capacity at this point in terms of our ability to run clinical studies um and uh will with the capacity we're building up also towards and many others. I think also worth mentioning in this context is that we're also collaborating with academic centers on some of our programs including auto 1ng and auto 8 where with the same types of processes, processes that we're running, our Auto 1 and Auto 3 programs.

48:49 Those are actually being run at the GMP facilities, at some of those academic partners as well. So we're actually having quite a network of capacity that we can work with, particularly for the earlier translational studies.

49:02 Okay, great. And then if I just follow up on maybe another question on the Auto 8 program, seeing that we're still on track for initiation in the second half here. Any kind of additional information on where we might hear some more about the design of the new cars that are in there? Maybe any pre-clinical data that kind of supports this advancement?

49:25 I think for now, we're obviously working on publishing quite a bit of our data across our programs and AutoAid. We're probably going to hold back a bit. We want to see kind of what the product actually behaves in the clinic. and then actually we'll make the determination of when and how to present. This program is obviously in a very competitive space and it's also frankly has to hit a very significant biological hurdle that we set for the program and so we'll want to actually run it out and see where we get to and we'll update in due time. Great, thank you. All right, thanks a lot. Thank you. Our next question comes from Greg from Goldman Sachs.

50:14 Hey, good morning and good afternoon. Thanks for taking my questions and congrats on the progress that you're making. I have two questions, if I could. The first is just on the competitive landscape, you know, we recently saw approvals for Monjuvi, which is, you know, in a second line setting for DLBCL and and Glenn Rupp, which is BCMA targeting asset and perhaps in a fifth line setting for multiple myeloma. So just with that in mind, could you just remind us how you're thinking about Auto 3 and Auto 8 respectively and how they are going to be positioned relative to those products? And then my second question is actually maybe that's for Andrew. I'm just thinking about as you advance particularly auto one and you're getting closer to potential filing and hopefully commercialization just trying to get a better sense of when as a company you guys are thinking about increasing investment around pre-commercialization activities or commercial infrastructure ahead of that thanks all right well thanks a lot for joining greg thanks for the questions

51:25 So with regards to competitive landscape, obviously within the DODCL segment, there's obviously quite a good number of programs that are active in the space. We had, as you pointed out, the recent approval of the CD19 monoclonal antibody for nephrosis and ZEN-COR, but there is also obviously quite a wide range of activities with bispecific antibodies, ADCs, as well as obviously a range of different types of CAR T approaches. So absolutely a competitive environment. With regards to the CD19 monoclonal antibody, I think the attractive part about that program and the current setting is that it's a setting where the patients actually have a hard time tolerating significant adverse events.

52:12 It's patients that are not eligible for an auto transplant and what we basically need for these patients is a a very well tolerated approach that still gives them an opportunity to actually get a longer lasting remission in that particular setting and that is really what the program managed to do combined obviously with a rather mild chemotherapy component which I think was the critical piece there to sort of create the therapeutic options for patients that otherwise would have a hard time taking on a lot of toxicity. So that is, I think, where that program is. When you look at the data in last line setting, the CRs actually come down dramatically. And there may be a 20%. Whether they're sustainable, I think it's too early to tell.

52:59 So they're very similar to other approaches that we've seen in last line setting and where, in fact, the CAR-T programs are set apart significantly. When you look at, you know, the and the other therapeutic modalities currently being tested. So I think that's important to keep in mind. What we see today with auto three is that we may be tracking above just carton long term remissions and we'll need to obviously have more data, more follow up to prove that. But the data today look very promising that we might be in good track to be to actually demonstrate a superior profile. So from that perspective, I think that landscape hasn't changed. I think there's a new component for patients that, you know, have limited ability to take toxicities.

53:56 And I think that is important and it does matter. But it also is a setting where you could see CAR-T actually moving as well and be highly active as well as where I would expect certainly from the data that we've seen across the various lines of therapy and the obesity I would expect. On Auto8, the BCMA ADC is active. There's no question about it. It does buy some time, but not an awful lot of time. When we look at basically the data we see in the field on the CAR-T side, be that Bluebird or be it the J&J program, particularly the J&J program has very significant, very deep molecular complete remissions and a very impressive data set. and substantially over and above we believe any of the other therapeutic modalities currently out there and we'll have to see kind of what ultimately ADCs and other therapeutic modalities fit in and how they're going to be slaughtered across the spectrum of lines of therapy and also the opportunity to potentially combine with other therapeutic modalities as well. So I think in that sense that the landscape hasn't changed in a significant way as far from our perspective and we still see you know very significant opportunity unchanged frankly for CAR T approaches with differentiated profiles in DLBCL and multiple myeloma.

55:17 Andrew you want to take the second one?

55:20 Yeah I do. Greg, thanks for the question. I mean, in terms of where we are talking about commercial, you know, sort of Randpup, et cetera, you know, that'll be a question I think will be addressed in 22. There's not a huge need at the moment for that. We're very fortunate that we have a very experienced commercial group, a very small commercial group, but a very experienced commercial group. You know, they're providing all of the thinking and the input that we need at this point. The physical sort of boots on the ground sort of thing is certainly a question that I'd be happy to talk to you about when we get to 2022.

56:13 Thank you very much. Thank you. Thank you. So it looks like that's all the time that we have for questions. The company will be happy to take any follow-up questions directly. And I'll now turn you back over to Dr. Christian Itin.

56:29 All right. Well, thank you all for joining us today. Great to actually be able to give you an update. Great to see many of you joining the call in the middle of August or the beginning of August here. So we're looking forward to the end of the quarter and update you on all the three. And then obviously at the end of the year, the ASH for the additional updates on both of our hemon programs and B-cell malignancies. With that, thanks a lot for your continued support and looking forward to also being in touch and keeping you updated. Thanks a lot, goodbye. Thank you for using the Compensating Center.