Q1 2020 Earnings Call

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Operator: BF-WATCH TV 2021 Ladies and gentlemen, thank you for standing by. And welcome to the Autolus Therapeutics First Quarter 2020 Financial Results and Operations Highlights Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero.

Ladies and gentlemen, thank you for standing by and welcome to the also less therapeutics first quarter 2020 financial results in operation highlights conference call.

At this time, all participants are in listen only mode.

After the speakers presentation, there will be a question answer session to ask a question. During this session you and he's a press star one on your telephone.

Please be advised that today's conference is being recorded.

If you weren't any thought assistance please press star zero.

Operator: I would now like to hand your conference over to your speaker today, Dr. Lucinda Crabtree, Vice President of Investor Relations. Thank you. Please go ahead, ma'am. Thank you, Cara.

I will now I'd like to hang your conference over to your speaker today Mr. excuse me Dr. Lucinda Crabtree, Vice President of Investor Relations. Thank you. Please go ahead ma'am.

Thank you Carl Good morning, Oh, good afternoon, everyone and thanks for taking Paulson today's cool financial results and when she want pilots and SCUSA Twentytwenty I'm using a country Vice President Investor Relations with me today on don't say Christian Austin, Our chairman and Chief Executive Officer Andre.

Lucinda Crabtree: Good morning or good afternoon, everyone, and thank you for taking part in today's call on the Financial Results and Operational Highlights for the first quarter of 2020. 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.

Lastly, on Chief Financial Officer.

Lucinda Crabtree: 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 well as discussions of potential risks, uncertainties, and 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 subsequent date for this presentation.

When we begin I would love to remind you that during the school, we will be making forward looking statements all statements other than statements of historical facts and tendon presentation. All forward looking statements.

Actual results performance or achievements, maybe materially different from those expressed or implied bus wouldn't statements for a discussion of the risks and uncertainties relating to our business. Another important boxes any of which could cause our actual results to differ from those contained in the board looking statements. Please see the section titled first factors in our annual reports on form 10.

Yeah, Paul on March the Twentytwenty as well as discussions the potential risks uncertainties and other important factors and out of the periodic filings with the FCC.

Lucinda Crabtree: So with that, on slide three, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the first 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 welcome your questions following our remarks. So with that, I'd now like to turn the call over to Christian. Thank you.

Christian Martin Itin: Thank you, Lucinda, and welcome to all of you, and thank you for joining us. I'm pleased to review our progress for the first quarter of 2020. In the first and last slide, we are pleased to report on a very productive first quarter. We remain on track with our clinical programs despite the challenges of COVID-19. As an organization, we have quickly adapted to this challenging environment, ensuring business continuity. Our focus has been on ensuring our clinical B-cell programs, Auto I and Auto III, continue to progress, and we remain on track with recruitment ongoing and manufacturing operations uninterrupted. As such, we expect to deliver data in the timelines that we have previously guided. While some of our participating clinical centers have been infection hotspots and had to pause enrollment for a few weeks, others could continue to work unaffected. We expect infections will continue throughout the year with flare-ups in places that were hit by the first wave of infections, while areas spared for now may see a rise in infections at some point in the upcoming month.

Christian Martin Itin: However, what is important to remember is that the patients we enroll in our trials have a very high medical need, no different from a severe COVID-19 patient, and the drive for centers to continue to treat these kinds of patients is very high. Typically, if a center gets under heavy pressure from COVID-19 infections, stem cell transplants and CAR T therapy are among the last procedures to be stopped and are among the first to resume post-peak infection. As many of you have analyzed, the time from establishing social distancing and stronger measures to reaching the other side of the first infection peak took approximately eight weeks in all impacted areas, irrespective of whether the measures were taken early or late relative to the rise of infections. The consistency of this infection pattern is helpful to anticipate the time of impact on a given center and catchment area.

Christian Martin Itin: Finally, we expect the increasing levels of preparedness and adjustments underway in the various healthcare systems and the continued implementation of social distancing measures will allow for continued treatment of these severely ill patients throughout the year. We expect that the adjustments we made for clinical trial operations and in our supply chain will remain relevant and in place for the duration of this infection cycle. Plus, the wider operational adjustments we made to minimize the risk of infection and exposure, as well as increase resilience to the risk of business interruptions, will also remain in place and, if necessary, will be adjusted.

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Allowed for continued treatment of these severely ill patients throughout the year.

We expect that the adjustments, we made for clinical trial operations and in our supply chain will remain relevant and in place for the duration of this infection cycle, plus divide or operational adjustments, we made to minimize risk of infection that exposure as well as increase resilience towards the risk of business interruptions will also remaining.

Place and if necessary will be adjusted.

Christian Martin Itin: With regard to our earlier stage programs, their monetary potential impact. At this point, we may see up to a quarter of delay depending on the program and the impact COVID-19 had on our respective academic or business partners. With that, and remaining on slide five, let me give you an overview of our corporate highlights.

With regards to our earliest stage programs here monitoring potentially impact at this point, we may see up to a quarter of delay depending on the program and the impact <unk> 19 hat on our respective academic or business partners.

Where's that and Romanian slight flies, let me give you an overview of our corporate highlights <unk>. The in April that the F. day, except at the I.D. application for all along our lead car T. product candidate for the treatment of adult patients with acute lymphoblastic leukemia, which allows us to initiate clinical sites and the company's first a little stuff.

Christian Martin Itin: We announced in April that the FDA accepted the IND application for Auto-One, our lead CAR-T product candidate, for the treatment of adult patients with acute lymphoblastic leukemia, which allows us to initiate clinical sites in the company's first overall study, Auto-One, AL-1, in the U.S. This followed the opening of the first site in the U.K. in March of this year, having received approval for the clinical trial applications by the MHRA earlier in the quarter. We expect to initiate dosing of our first patient in this study this quarter and remain on track to provide full data by the end of 2021. With regard to our lead product candidate for the treatment of DL-BCL auto 3, the Phase 1-2 Alexander study is ongoing. The timing of the program remains on track, and we will update on the decision for Phase 2 in mid-2020, as previously guided.

Auto loan Ala bomb in the U.S.

This call it at the opening out the first side to the U.K. March of this year, having received approval of the clinical trial applications by the M.H. already earlier in the quarter.

We expect to initiate those thing of our first patients in this study this quarter and remain on track to provide full date up at the end of 2021.

<unk> pulled out candidate for the treatment F.D.L.D.C.L. auto asleep. The phase one two Alexander's study is ongoing the timing of the program. The writings on track and we'll we'll update on station for face too and make 2020 as previously guide it.

Christian Martin Itin: We're excited about our DLDCL program and its broader market potential following the positive data update we provided at the EHA-EBMT CAR T-cell meeting in February 2020. Our Chief Scientific Officer, Dr. Martin Poulet, presented early, encouraging signs of sustained, complete responses achieved with low toxicity and minimal patient management requirements. We're now planning to add a 20-patient cohort to the ongoing Alexander study in the second half of this year, with patients treated in an outpatient setting, which I will expand on a little later in this call. The last item I wish to touch on in this slide is our forthcoming clinical data updates expected through May and June. For Order 1 in Adult DLL, we plan to present updated data at the virtual EHA meeting in June with approximately six months of additional follow-up post our ASH 2019 data. For Auto 3, we're planning to present updated data at ASCO in an oral session. We will also follow up with a similar presentation at the EHA meeting two weeks later. We plan to present both sets of data to investors in calls shortly following this virtual conference. Moving to slide six.

We're excited about R.D.L.D.C.L. program and it's brought market potential following the positive date update we've provided at the E.H.A.E.M.T. car T. cell meeting in February 2020.

T Scientific officer dark market Palais presented early encouraging signs of sustained complete responses to change with low toxicity at minimal patient management required.

Right now planning to added plenty patient cohort to the ongoing Alexander study and second half with this year with patients treated in an outpatient setting, which I will explain expand on a little later into in this call.

The last item I wish to touch on into slide is our forthcoming clinical data updates expect it through may and true.

For auto bomb in adult daily L., we plan to present updated data at the virtual E.H.A. meeting in June with approximately six months of additional follow Posner Ash 2019 data cuts.

For all the three were planning to present updated date ASKO in an oral session.

Will also follow up with a similar presentation at the E.H.A. meeting two weeks later.

We planted present, both sets of data to investors in cold shortly following these virtual conferences.

To slide six in addition to our lead to need <unk> clinical candidates were planning a series of pre clinical data updates on some of our pipeline programs A.C.R. two in late June.

Christian Martin Itin: In addition to our two lead clinical candidates, we're planning a series of preclinical data updates on some of our pipeline programs at AACR2 in late June. We have been invited to make an oral presentation on our prostate cancer program, AUTO7, and also have poster presentations planned for both AUTO6-NG in small cell lung cancer as well as AUTO5 as an assistive program to AUTO4 in T-cell lymphoma. Much like ASCO and DHA, we're planning an investor call that will shortly follow these presentations at AACR2. Finally, I would like to thank our partners at the Cell Therapy Catapult and the GSK site organization and Stevenage for their continued support that enabled us to maintain operations throughout the peak infection and support the critically ill patients in our trial. Moving to slide seven.

We have been invited to make an oral presentation on our prostate cancer program or a seven an old sounds poster presentations bound for both auto six N.G. in small set of lung cancer as well as auto five sister program to order for N.T. cell lymphoma.

Like ask on D.H.A., we're planning an investor cold that little shortly followed these presentations A.C.R. too.

Finally, I would like to thank our partners that the cell therapy catapulted into the G.S.K. side organization and Stephen H., where they continued support that enabled us to maintain operations through at the peak infection and support the critically ill patients in out of trials.

[noise] moving to slide seven.

I wanted to spend a brief moment recapping on our lead program auto loan in it all to L.

Christian Martin Itin: I wanted to spend a brief moment recapping on our LEAP Program Model 1 in Adult ALL. Relapsed refractory adult ALL is a challenging disease often impacting elderly patients. A lot of these patients have significant comorbidities, making them a fragile patient group to treat. The indication is approximately three times the size of relapsed refractory pediatric ALL and represents an attractive market opportunity. Within the U.S. and the top five European countries, approximately 3,000 patients every year are at the end stage of treatment, having failed chemo and transplant and therefore requiring other options. However, at this point, there is no CAR-T therapy approved for adult ALL. Obviously, there are a number of programs that are being tested. However, all of them have experienced significant challenges with the management of the toxicities.

Well lapsed refractory at all to L.L. is a challenging disease, and often impacted and elderly patients a lot of these patients have significant cold morbidities, making them in France, an outpatient group to treat.

The indication is approximately three times the size of relapse Refracture pediatric Gail and represents an attractive market opportunity.

Within the U.S. and the top five European countries, approximately 3000 patients every year I didn't end stage of treatment, having failed chemo transplant and therefore, requiring other options.

At this point, there's no karkhi therapy approved for it all day L.L.. Obviously, there are a number of programs that are being tested however, all of them have experience significant challenges with the management of the toxicities.

Well, we created like the old alone is a product that is designed to behave physiologically engages target cells like a normal piece of wood.

First generation car T. products share the identical binder to C.D. 19 is this true for <unk> start to analyze of so.

Spider has a slow off right from the C.D. 19 targets and as a consequence wants the car t. cell binds to the other team U.S.L. and has to live with the tax and tried to talk sick payload. It has difficulty letting go from the targets L. and get stuck.

Christian Martin Itin: What we created with Auto-One is a product that is designed to behave physiologically and engage target cells like a normal T-cell would. First-generation CAR T products share the identical binder with CD19. This is true for Kymriah, Triscarta, and Lysosome.

When you have a car t. cells <unk> when you have car t. cells getting stuck to target cells. They continue to be activated which dry side, a kind of release and bounce adverse events. In addition to leading to side a kind of really syndrome. This continued activation of the car t. cells can drive exhaustion, which negatively impacts per systems.

Christian Martin Itin: This binder has a slow off-rate from the CD19 target. As a consequence, once the CAR T cell binds to the leukemia cell and has delivered the taxocytotoxic payload, it has difficulty letting go of the target cell and gets stuck. When CAR T cells get stuck to target cells, they continue to be activated, which drives cytokine release and thus adverse events. In addition to leading to cytokine release syndrome, this continued activation of the CAR T cells can drive exhaustion, which negatively impacts persistence. So there is a fundamental challenge with that type of engagement.

So there's a fundamental challenged with that type of engagement.

In contrast, what we created with auto loan is a car keep product that mimics the behavior and the binding kinetics, Oh physiological t. cell with a very fast off rate and then the ability to disengage relatively rapidly after delivering to kill.

The result is reduced side to kind of of these and also in increasing targets l., killing as the car t. cells are freed up more quickly and can reengage new leukemia cells.

In addition car t. cells can expand more readily leading to more active car t. cells in the patients body capable of fighting for leukemia.

Christian Martin Itin: In contrast, what we created with AUTO1 is a CAR T product that mimics the behavior and the binding kinetics of a physiological T cell with a very fast off-rate and an ability to disengage relatively rapidly after delivering the kill. The result is reduced cytokine release and also an increase in target cell killing, as the CAR T cells are freed up more quickly and can re-engage new leukemia cells. In addition, CAR T-cells can expand more readily, leading to more active CAR T-cells in the patient's body capable of fighting the leukemia. Now, turning to slide 8.

Now turning to slide eight.

What we show on the left hand side is the data for playing a to them admirably insight, though which is the current standard of care in this disease setting.

What is important to understand is that the patients that we have treated on our child and at that we highlighted what we highlighted the dash is that the patients are not have mostly on the gone and failed stem cell transplant. In addition, approximately 60% of patients have been on <unk> and failed.

Christian Martin Itin: What we show on the left-hand side is the data for Blinatumab or Blincito, which is the current standard of care in this disease setting. What is important to understand is that the patients that we have treated on our trial and that we highlighted, and what we highlighted at ASH, are mostly patients who have mostly undergone and failed a stem cell transplant. In addition, approximately 60% of patients have been on inotuzumab or blinitumab and failed. Thus, our data is based on a patient population with more advanced disease compared to the data shown for the Blenner tumor. However, what you see in the Blinatumumab results is that the CR rate in that population is about 40%, with an event-free survival of about 30% at six months, and in fact, most patients relapse within less than a year. When we look at the safety profile, BlinkCyto shows a good safety profile overall, and in fact, the product is typically delivered in an outpatient setting.

Or a date ice based on a patient population with more advanced disease compared to the data showing triply and a tune that.

However, what do you see independent to a map results is that the C.R. rate in that population is about 40% with an event free survival.

30% at six months and in fact, most patients relapse within less than a year.

When we look at the safety profile Blink site those shows a good safety profile over old and in fact, the product is typically delivered in an outpatient setting.

Mad when we look at our own data for auto loan. If you look at the total data set the 16 patients you have an overall c. or rate of 87% and a half an event free survival of 68% at six months. So in a simple way we have around twice the activity that was reported with Linda to map, where the comparable safety profile.

We have <unk> no patience with Highgrade side to kind of release syndrome, and we have 90% of the patients with high great toxicity.

Oh patients with high great.

City had a very high tumor burdening, the marrow off more than 50%.

Going forward will manage these patients went to north toxicity starts to build to minimize highgrade adverse events.

Christian Martin Itin: Now when we look at our own data for auto one, if you look at the total data set of 16 patients, you have an overall CR rate of 87% and then have an event-free survival of 68% at six months. So, in a simple way, we have around twice the activity that was reported with Blenner Tumor Map with a comparable safety profile. We have had no patients with high-grade cytokine release syndrome.

Finally, I just wanted to touch on the subset of patients that were treated with the close commercial manufacturing process.

You can see that the data if anything looks somewhat better than the total overall, which includes patients that were treated with product that was manufactured by hand with a conventional manufacturing process.

So based on this data on turning to slight nine we decided to move the program forwarding to pivotal study.

<unk> was filed in the U.K., including two <unk> Rolling currently the U.K. The U.S.I.D. also is now open and we're opening up centres in the U.S. with the <unk> aim enrolling patients in the second core.

Christian Martin Itin: And we have 19% of the patients with high-grade neurotoxicity. All patients with high grade neurotoxicity had a very high tumor burden in the marrow of more than 50 percent. Going forward, we will manage these patients when the neurotoxicity starts to build to minimize high-grade adverse events. Finally, I just wanted to touch on the subset of patients that were treated with the closed commercial manufacturing process. You can see that the data, if anything, looks somewhat better than the total overall, which includes patients that were treated with a product that was manufactured by hand using a conventional manufacturing process. So based on this data, I'm turning to slide nine. We decided to move the program forward into a pivotal study. The CTA was filed in the UK and cleared in Q1, and we're currently enrolling patients in the UK.

As a reminder, this is a single on 100 patients study with relapsed refractory patients the primary endpoint to see alright, and secondary endpoints include molecular C.R.'s fan free survival and duration of response, we remain on track to complete involvement in the first chance of next year.

To what extent, we may be impacted by the call. It 19 situation going forward. So we'll have to see but we currently expect the impact to be limited.

I plan to deliberate data up at the end of Twentytwenty bones remain on track.

No turn to slide 10, where I would like to switch gears and talk about auto Sweet a program that is designed for the treatment of patience with diffuse large b. cell lymphoma.

Third line D.L.D.C.L. is about four times bigger an indication and then relapse refractory at all to L.L. and the setting with all ready to approve car T. therapy products with just <unk> plus license l. or take her 17 expected to be approved later this year, we're beginning of next year.

Christian Martin Itin: The US ID is also now open, and we're opening up centers in the US with the aim of enrolling patients in the second quarter. As a reminder, this is a single-arm, 100 patient study with relapsed refractory patients. The primary endpoint is CR rate, and secondary endpoints include molecular CRs, vent-free survival, and duration of response. We remain on track to complete enrollment in the first half of next year. To what extent we may be impacted by the COVID-19 situation going forward, we'll have to see, but we currently expect the impact to be limited. Our plans to deliver data by the end of 2021 remain on track.

We know this is a large opportunity with approximately 10000 patients in the back end up the disease, which is a sizable population with a very significant medical neat.

In terms of the outlook for those patients. They have typically run through a series of chemotherapy combinations often with them on a clone lansky body and they also have received the transplant. If there were eligible for it if not they go directly to salvage therapy.

Car T. therapies are approved in the third line or salvage therapy, setting with trials ongoing and patients in second line setting.

Christian Martin Itin: Let's now turn to slide 10, where I would like to switch gears and talk about Auto3, a program that is designed for the treatment of patients with diffuse large B-cell lymphoma. Third-line DL-BCL is about four times bigger an indication than relapsed refractory at ALT-LL and a setting with already two approved CAR-T therapy products, which are SCART and Chimraya, plus Lysazel or JCAR-17 expected to be approved later this year or beginning of next year. We know this is a big opportunity with approximately 10,000 patients on the back end of the disease, which is a sizable population with a very significant medical need. In terms of the outlook for those patients, they typically have run through a series of chemotherapy combinations, often with a monoclonal antibody, and they also have received a transplant if they are eligible for it. If not, they go directly to salvage therapy.

There are two things that we see as being really important for successful treatment and commercial uptake in D.L.D.C.L.

First you have to induce complete permissions that are lasting this is a disease setting where you aim for cure.

Second is that you actually have to have a therapy that can be administered where the patients are situated.

Today in the U.S. approximately 80% of the patients are treated outside of University hospitals, and only about 10% of the patients are treated as University hospital inpatients. It is this population that is primarily treated with car t. therapies.

The key challenge for treatment 10th is is the need for intense patient management, which has limited the use of car tea outside of the University hospital inpatient setting.

What we're looking for an auto three is a highly high level of sustained complete permissions. In addition, we're looking for a safety profile that can be managed in non academic outpatient settings to reach the majority of patients.

Moving to slide 11.

Across the car T. popular programs in D.L.D.C.L., we observe a fairly high overall response rate yet the sustained complete response rate is limited it is somewhere between 30 and 40% depending on the program and a subset of indications that were treated or included in the respective trials.

Christian Martin Itin: CAR T therapies are approved in the third liner salvage therapy setting with trials ongoing in patients in the second line. There are two things that we see as being really important for successful treatment and commercial uptake in DLDCL. First, you have to induce complete remissions that are lasting. This is a disease setting where you aim for cures. Second, you actually have to have a therapy that can be administered where the patient is situated. Today, in the U.S., approximately 80% of patients are treated outside of university hospitals, and only about 10% of the patients are treated as university hospital inpatients. It is this population that is primarily treated with CAR-T therapy. The key challenge for treatment centers is the need for intense patient management, which has limited the use of CAR-T outside of the university hospital inpatient setting. What we're looking for in Auto III is a high level of sustained complete remissions. In addition, we're looking for a safety profile that can be managed in non-academic outpatient settings to reach the majority of patients. Moving to slide 11.

Roughly a third of the complete responses are lost early on typically within the first three to six months.

There are two key mechanisms reported that are likely driving relapse lost a C.D. 99 digits in about 30% to 50% of the patients.

That time of relapse and P.D. <unk> checkpoint upregulation in about two thirds of the patients at time of free Naps.

Looking at safety, but the commercial T.D. 19 cars, there's significant amount of management of those patients required to address severe side to kind of release syndrome and in particular in particular as well as to severe neurotoxicity.

Typically these toxicities happened early onset and require intense patient management that monitoring meaning patients are largely confined to classical hospitalized patients setting.

We designed to program with a dual targeting approach having two independent receptors in each car t. cells individually designed and optimized for the respect his target antigen to minimize the impact the C.D. 19 antigen loss. We also kind of the P.D.L. <unk> Upregulation and check point based escape of lymphoma cells, where the single though September.

Christian Martin Itin: Across the CAR-T programs in DLD-CL, we observe a fairly high overall response rate, yet the sustained complete response rate is limited. It is somewhere between 30 and 40 percent, depending on the program and the subset of indications that were treated or included in the respective trial. Roughly a third of the complete responses are lost early on, typically within the first three to six months.

<unk> the day before infusion of order three providing to cover it to achieve a C.R. and sustain it.

Oh, there three has shown a high level of C.R.'s in the dose escalation face with the current study.

Present, the further updated ask.

It it's worthwhile, noting that the high level of complete <unk> without a inducing hike rate C.R.S. or side to kind of release syndrome, and no neurotoxicity of any great into patients toast at 152 450 million sell doses.

Christian Martin Itin: There are two key mechanisms reported that are likely driving relapse, loss of CD19 antigen in about 30 to 50 percent of the patients at time of relapse and PD-L1 checkpoint upregulation in about two-thirds of the patients at time of relapse. Looking at safety, with the commercial CD19 cars, there is a significant amount of management of those patients required to address severe cytokine release syndrome, and in particular, in particular, as well as severe neurotoxicity. Typically, these toxicities have an early onset and require intense patient management and monitoring, meaning patients are largely confined to classical hospital inpatient settings. We designed a program with a dual-targeting approach, having two independent receptors in each CAR T-cell, individually designed and optimized for the respective target antigen, to minimize the impact of CD19 antigen loss. We also counted the PD-L1 up-regulation and checkpoint-based escape of lymphoma cells with a single dose of pembrolizumab on the day before infusion of order 3, providing the cover to achieve CR and sustain.

Contrast is remarkable.

It's also important to notice that with all the way, we we have not managed to patients actively for adverse events.

Now to talk about the extent of the total addressable market. This profile enables us to potentially we reach let's continue to slide 12.

Currently proof products are only tapping into a a.

Proportion of substantially less than 20% of the market opportunity, which is managed by the academic centers, there's very little to no penetration to the rain, 80% of the market, which comprises settings that cannot deal with the intensity of patient management required for the current karkhi products.

We believe this creates an enormous opportunity for the profile off a product that we're seeing with all the sweet and as such we believe that the program has a unique potential going forward.

Back to provide an updated asked on the clinical profile of the program.

So let us turn to slide 13.

Would like to outline how we can build them this potential patient profile.

Given behind a differentiate clinical and safety profile being reported so far we see an attractive opportunity for auto three years in an outpatient solution for patients with the L.D.C.L. there for maximizing the commercial potential of car t. products across old settings with care this disease.

Christian Martin Itin: Order 3 has shown a high level of CRs in the dose escalation phase of the current study, and we will present a further update at ASCO. It is worthwhile noting that the high level of complete remissions were obtained without inducing high-grade CRS, or cytokine release syndrome, and no neurotoxicity of any grade at the patient's dose at 150 to 450 million cells. This is a very unusual finding

Such were planning to add a 20 patient quarter ongoing phase one two Alexandra study in the second half of this year with patients treated in an outpatient setting in order to broaden our understanding of the feasibility S.I. patient administration.

<unk> I will turn over the cold to Andrew for our first quarter 2020 financial updates Andrew.

Christian Martin Itin: When you compare this profile to the Cheskarta, Kymriah, and JCR17 data, the contrast is remarkable. What is also important to note is that with Auto III, we have not actively managed patients for adverse events. Now to talk about the extent of the total addressable market this profile enables us to potentially reach, let's continue to slide 12. Currently, approved products are only tapping into a proportion of substantially less than 20% of the market opportunity, which is managed by the academic center.

I think it's Christian and good morning or.

We live to slide stain. It sets my placement for you out financial results full date this quarter of 2020.

Hmm.

<unk> operating expenses for the same amount of sending much. So do you on 2020 or $38.6 million that was net income Oh $300000 on that compares to its operating expenses buggy point $2 million <unk> granting kind of those 2 million dollar.

Christian Martin Itin: There's very little to no penetration in the ring 80% of the market, which comprises settings that cannot deal with the intensity of patient management required for the current CAR-T product. We believe this creates an enormous opportunity for the profile of a product that we're seeing with Auto III, and as such, we believe that the program has unique potential going forward. We expect to provide an updated ask on the clinical profile of the program. So, let us turn to slide 13.

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Same period in 2019.

The increase switch to in general to they continued increasing clinical trial activity.

Which is expected to deliver on K. milestones throughout the rest 2020 also increased head count and an increase in public company costs literally related to insurance.

Research and development expenses increased $31.3 million for the same up at lunch and did manage to do you want Twentytwenty, that's up from $22.6 million for the same period in 2019.

Christian Martin Itin: I would like to outline how we continue to build on this potential patient profile. Given the highly differentiated clinical and safety profile we have reported so far, we see an attractive opportunity for Auto3 as an in- and outpatient solution for patients with DOPCL, therefore maximizing the commercial potential of CAR-T products across all settings of care in this disease. As such, we're planning to add a 20-patient cohort to our ongoing Phase I-II Alexander study in the second half of this year, with patients treated in an outpatient setting, in order to broaden our understanding of the feasibility of outpatient administration.

Cash costs, which exclude depreciation and amortization as well as shape based compensation increase to $25.6 million from 17, and a half million dollars.

The increase in R. and D. cash costs, that's $8.1 million, consisting primarily of an increasing compensation related costs at $2.2 million.

Increase an employee head count that supports the advancement of that part candidates as well as an increase $3.7 million in in project expenses associated with clinical activity and that includes the research process development manufacturing activities are necessary to conduct their studies.

Christian Martin Itin: With that...

Andrew Oakley: And with that, I will turn over the call to Andrew for our first quarter 2020 financial update.

Andrew Oakley: Thanks, Christian, and good morning or good afternoon to everyone. If we move to slide 15, it's my pleasure to review our financial results for the first quarter of 2020. Net total operating expenses for the three months ending March 31, 2020 were $38.6 million, net of grant income of $300,000, and that compares to net operating expenses of $30.2 million, net of grant income of $2 million for the same period in 2019. The increase was due, in general, to the continued increase in clinical trial activity, which is expected to deliver on key milestones throughout the rest of 2020. Also, increased headcount and an increase in public company costs primarily related to insurance. Research and development expenses increased to $31.3 million for the three months ended March 31, 2020, and that's up from $22.6 million for the same period in 2019.

Plus an increase of $1.8 million in licenses legal fees consulting services would show some of which is related to an option to negotiate a future license as well as I.T. infrastructure and support at the remainder was attributable to other additional costs the amount of about $400000.

General administrative expenses decreased the $7.6 million for the three months and indeed, much though do you well that's down from $9.6 million for the same period in 2000 in 19.

Cash costs, again, which exclude depreciation as well as associate based compensation.

Decreased to $5.9 million from $6.3 million.

Compensation related expenses database, but $300000 and I'd say communicate telecommunication of general costs decrease but by the same amount.

<unk> also the same amount in commercial cost that was off all upset by an increase in public company costs.

Andrew Oakley: Cash costs, which exclude depreciation and amortization, as well as share-based compensation, increased to $25.6 million from $17.5 million. The increase in R&D cash costs, which was $8.1 million, consisted primarily of an increase in compensation-related costs of $2.2 million due to an increase in employee headcount that supports the advancement of our product candidates, as well as an increase of $3.7 million in project expenses associated with a clinical activity that includes the research, process development, and manufacturing activities necessary to conduct the studies, plus an increase of $1.8 million in licenses, legal fees, and consulting services The remainder was attributable to other additional costs of about $400,000.

Half a million dollars, which <unk> primarily relates to insurance as I had previously mentioned.

No no cash costs are within the G.N.A. area date craze to $1.7 million for the three months ending much 31 and that can taste frequent $3 million for the same period into 2019, but they craze haiti's pretty that until two basically she had base.

Sensation expense, which decreased by $1.6 million as a result of below that.

<unk> most during the period.

Well, let loss attributable to ordinary shareholders is 29.9 million for the three months ending much. So do you want to 2020 and that compares to $27.2 million for the comfortable period in 2019.

Cash cash equivalents at the end of the quota today's little to $243.3 million and that compares at $210.6 million that we had at the end of December 2019.

Andrew Oakley: General and administrative expenses decreased to $7.6 million for the three months ending March 31, and that's down from $9.6 million for the same period in 2019. Cash costs, again, which exclude depreciation as well as share-based compensation, decreased to $5.9 million from $6.3 million. Compensation-related expenses decreased by $300,000, and IT, telecommunication, and general office costs decreased by the same amount, and there was a decrease, also by the same amount, in commercial costs, but that was all offset by an increase in public company costs of around half a million dollars, which primarily relates to insurance, as I have previously mentioned. Net non-cash costs within the G&A area decreased to $1.7 million for the three months ending March 31, and that compares to $3.3 million for the same period in 2019.

And as such we anticipate that that cash on hand provides us with a runway into 2022.

And with that Oh, no hand in the cold. That's the question to give you a brief outlook on expected milestones Christian.

Thanks, Andrew Let me conclude this part of the management discussion with a review of the upcoming milestones at news flow through 2020, it's moved to slide 17.

Upcoming eight months will be an end full period for us with multiple clinical milestones and opportunities for value creation.

Mostly <unk> imminent operational focus he used to conduct always sales are pivotal trial for auto loan and the L.A.L.L.

We expect to report clinical data across multiple programs, including updated updated all those three Alexandra data out the forthcoming ASKO meeting an updated auto one old car 19 data as well as auto three data E.H.A.S. previously mentioned.

Well look to progress or number of our other preclinical candy gets through the second half of 2020, and they're looking forward to providing preclinical data updates and I was solid tumor programs auto six Angie auto seven or eight A.C.R. as well as R.T. cell lymphoma program with all the five.

Andrew Oakley: The decrease here is attributed to basically share-based compensation expense, which decreased by $1.6 million as a result of the lower value of stock options that were recognized during the period. The net loss attributable to ordinary shareholders was $29.9 million for the three months ending March 31, 2020, and that compares to $27.2 million for the comparable period in 2019. Cash and cash equivalents at the end of the quarter totaled $243.3 million dollars, and that compares with $210.6 million dollars that we had at the end of December. And as such, we anticipate that that cash on hand provides us with a runway into 2022. And with that, I will now hand the call back to Christian, who will give you a brief outlook on expected milestones.

Finally towards the end of the year, we look forward to priding further data updates on both.

Auto loan or three as we expect for the end of the year in conclusion on flight 18, I'd like to recap the major messages from two days cold first auto bombings or if a person odalis program to move into pivotal stage, given the positive safety and efficacy profile today, the belief that autobahn has the potential.

Be a best in class C.D. 19 car T. program in adult they L.L. a disease setting with a very high unmet medical neat.

Secondly, with regards to Odyssey, and D.L.D.C.L., which is expected them slated for additional clinical data updates <unk> Che.

To conduct an outpatient court in the second half of this year.

The company is an excellent position combined with a strong balance sheet, which Brooklyn, Isis around right into 2022, <unk>, yeah, but in a good position I think are looking forward to an exciting second half a year when I'm happy to take questions. Thank you.

Christian Martin Itin: Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through 2020. Let's move to slide 17. The upcoming eight months will be an endless period for us with multiple clinical milestones and opportunities for value creation. Our chief and most imminent operational focus is the conduct, obviously, of our pivotal trial for ARDUAN in adult ALL. We expect to report clinical data across multiple programs, including updated Auto 3 Alexander data at the forthcoming ASCO meeting and updated Auto 1 Old Car 19 data, as well as Auto 3 data at EHA, as previously mentioned. We will look to progress a number of our other preclinical candidates through the second half of 2020 and are looking forward to providing preclinical data updates on our solid tumor programs, Auto 6-NG and Auto 7 at AACR, as well as our T-cell lymphoma program with Auto 5.

Okay.

Question, you need to press star one I get telephone.

Question press the pound key please.

<unk>.

Yeah Press question costs on line of chatting isn't that with me.

Company.

Everyone listen and get on for a child and congratulations on the progress and and a difficult environment.

Just just a couple of questions from me.

You discuss kind of the challenges that are related to.

<unk> hypothetically what would you consider more important.

Accessibility or the duration of and deep mess up response.

Well that's it off for joining the really appreciate it the I think with regards to D.L.D.C.L. you you won't you need those aspects actually to be addressed you need a high level of sustained C.R.'s.

And you need an excellent safety profile to reach the population both aspects are important in the belief that that we have an ability to making significant improvement on both sides with the program.

Christian Martin Itin: Finally, towards the end of the year, we look forward to providing further data updates on both Auto I and Auto III, as we expect for the end of the year. In conclusion, on slide 18, I'd like to recap the major messages from today's call. First, Auto I is our first Autolus program to move into the pivotal stage. Given the positive safety and efficacy profile today, we believe that Auto I has the potential to be a best-in-class CD19 CAR-T program in adult ALL, a disease setting with a very high unmet medical need.

So you do not consider one more important than the other.

Sense.

Well, there's you know it is a it's a life threatening disease. The first thing you have to make sure is the patience device. So getting too long term remission news walk the walk the ultimate goal is but then you also have to make sure that the patient has access to the therapy and right now in the U.S., they're only about 10% of the patients in that it's east setting that.

Access to Karkhi therapy, because it is confined to the inpatient segment of the centres of excellence and that has actually create a situation where while there was a big demand for these types of therapist. The actual access tech can be realized is very very small I'm not he's old the actual intensity of them.

Christian Martin Itin: Secondly, with regard to Order 3 in DLBCO, which is expected and slated for additional clinical data updates at ASCO and EHA, we plan to conduct an outpatient court in the second half of this year. The company is in an excellent position, combined with a strong balance sheet, which provides us with a run rate into 2022. We feel we're in a good position and, I think, are looking forward to an exciting second half of the year. We're now happy to take questions.

Management off these patients during the adverse events that occur in the at the onset of the therapy and how they sort of the key reason for the confinement today is a relatively small number centres. So you have to make fundamentally have the impact on the disease.

Well up and sustain see our rates gives you, but then you actually have to have the safety Purple front allows you to further expand the delivery of this type of therapy to centres beyond the the relatively small numbers of academic centers of excellence.

Operator: As a reminder, to ask a question, you need to press star 1 on your telephone. To withdraw your question, press the pound...

Operator: Please stand by while we compile the Q&A roster. Your first question comes from the line of Chad Mesner with Miyahama. Hi everyone, this is Gil on behalf of Chad and congratulations on the progress in a difficult environment. So just a couple of questions from me. You discussed the challenges that are related to... and DLBCL. Hypothetically, what would you consider more important, patient accessibility or the duration and deepness of response?

Alright, thank you.

And we are very much looking forward to seeing some of the pretty clinical data. The second half of Ah I see our I I know that that it looks like auto six N.G. data would be per than than that small cell lung cancer. So that's a very interesting indication not just because of the target, but also because they lack of you know.

I mean, it's a necessity that that scene and a lot of these cells kind of maybe you could you know kind of Orient us what kind of data we should be expecting add I I see are.

Christian Martin Itin: Well, thanks a lot for joining me. I really appreciate it.

Christian Martin Itin: I think with regard to DLBCL, you need both aspects to be addressed. You need a high level of sustained CRs, and you need an excellent safety profile to reach the population. Both aspects are important, and we believe that we have the ability to make significant improvements on both sides of the program. So you do not consider one more important than the other.

So do you see are we going to be presenting are obviously preclinical data on these from these programs as you may remember the way we designed the programs is actually to include.

A set off a self programming modules step in and you know enabled the sales.

Do have a higher resilience and higher ability to cope with the challenging microenvironments that we find in in these particular sets of customers.

Christian Martin Itin: and the other in this instance.

Christian Martin Itin: Well, you know, it's a life-threatening disease, so the first thing you have to make sure is that the patient survives. So getting to a long-term remission is the ultimate goal, but then you also have to make sure that the patient has access to the therapy. Right now, in the U.S., there are only about 10% of the patients in that disease setting that have access to CAR T therapy because it is confined to the inpatient segment of the Centers of Excellence. And that has actually created a situation where while there is a big demand for these types of therapies, the actual access that can be realized is very, very small. And that is all on the actual intensity of the management of these patients during the adverse events that occur at the onset of treatment.

And that is going to be a key part of the all the data that we're going to be presenting his.

The used to those modules in those settings and the impact the modules has to actually gave us a appropriate level of activity. Indeed, as you point that very challenging a tumor environments.

Excellent then and just some kind of last clarification, you're expecting to complete enrollment and the pivotal study.

By your and 21 first Athleta late.

Up next year for first testing first half next year, we stayed the year on year <unk>. Okay. Thank you that's what I thought they care for taking like questions and congratulations on them on your progress.

Christian Martin Itin: And that is sort of the key reason for the confinement to this relatively small number of centers. So you have to make fundamentally have an impact on the disease. That is what the sustained CR rates give you. But then you actually have to have a safety profile that allows you to further expand the delivery of this type of therapy to centers beyond the relatively small numbers of academic centers of excellence.

Thanks, Thanks for joining.

Yeah and ask questions <unk>.

Oh security.

Oh, Thank came out try taking the question I can just ask on the on off three outpatient program can you just talk a little bit about what the profile that patient with look like <unk> inpatient you know within the content to the extent that you can discuss protocol on that basis and then just also.

Christian Martin Itin: All right. Thank you.

Christian Martin Itin: And we are very much looking forward to seeing some of the preclinical data at the second half of AACR. I noted that it looks like auto 6NG data will be presented in small cell lung cancer. That's a very interesting indication, not just because of the target but also because of the lack of immunogenicity that's seen in a lot of these cells. Maybe you could kind of tell us what kind of data we should be expecting at the AACR.

Caroline a little bit on that sort of go now go decision as well I collected later M.P.R.N. a decision tree that will help you get cancer, making that decision. If you could just got that.

Yeah, alright, thanks for joining so in terms of the the the patient to patients actually we don't expect to look different.

From the the the patients that we've treated so far that the reason why you treat the patients in in in in patient setting with a car in a car t. programs is not because with the state the patient day and they easy, but it's the consequences of toxicity induced at the onset.

Christian Martin Itin: So at NACR, what we're going to be presenting are obviously preclinical data from these programs. As you may remember, the way we designed the programs is actually to include a set of cell programming modules that enable the cells to have higher resilience and higher ability to cope with the challenging microenvironments that we find in these particular sets of tumors. And that is going to be a key part of the data that we're going to be presenting, the use of those modules in those settings and the impact the modules have on actually giving us an appropriate level of activity in these, as you point out, very challenging tumor environments.

Of the therapy that you're providing.

So there is not we don't expect to see a difference in the patients and in fact, you know as you can imagine with the majority of the patients treated outside of the academic centers. The patients are are in in a in a reasonable condition and can obviously normally manage be managed in you know college at clinics and net.

Works etcetera, much more on the periphery healthy off the the health care system.

Christian Martin Itin: Excellent. And just some kind of last clarification. You're expecting to complete enrollment in the pivotal study by year-end 21, or just data-based? First half next week.

So we expect the same patients, but obviously, we're treating them in a slightly different settings. Then both the what the impatient setting is so this is not a difference of the patients. It's a difference the level of patient management required to actually get these patients safely through the therapy and <unk>.

Christian Martin Itin: First half of next year, with data at year end for next year.

Christian Martin Itin: Okay, thank you; that's what I thought. Thank you for taking my questions and congratulations on your progress.

Three is actually and anything else to to explore.

Christian Martin Itin: Thanks a lot. Thanks for joining us.

Christian Martin Itin: Your next question comes from the line with Mara Goldstein, Health Secure. Thanks very much for taking my question. If I could just ask, on the Auto III outpatient program, can you just talk a little bit about what the profile of that patient would look like relative to inpatient, you know, within, to the extent that you can discuss protocols on that basis? And then also, if I could drill in a little bit on the sort of go-no-go decision as well, expected later this year, and the decision tree that will help you get to making that decision, if you could discuss that.

Okay.

And then with regards to decision points, obviously, we're going to provide an update the where we are with the program with ASKO that gives us a very good view on the on the response rate level. We will have additional follow up that we'd like to see which gets into a slightly into the second half of the year at which point <unk>.

What the sustain see our rates looks like and that will be the key piece of information that will inform us on the path for it and as you can imagine getting the data from D.I. patient cohorts with also enabled us to actually design, a pivotal study somewhat differently, including i. patients an outpatient setting into pivotal studying.

Christian Martin Itin: Yeah, hi Mara, thanks for joining us. So in terms of the patients, the patients actually, we don't expect them to look different from the patients that we've treated so far. The reason why you treat patients in an inpatient setting with the current CAR T programs is not because of the state the patient is in, but because of the consequences of the toxicity induced at the onset of the therapy that you provide. So, we don't expect to see a difference in the patients, and in fact, as you can imagine, with the majority of the patients treated outside of the academic centers, the patients are in a reasonable condition and can obviously normally be managed in oncology clinics and networks, et cetera, much more on the periphery of the healthcare system.

Which we believe would actually be a very important component they'll say oh, the pivotal program. So that data will be very informative in in terms of the design of this study as well.

Thank you happy.

Thank you ma'am.

Yeah and ask questions.

<unk>.

I see mine right.

Hi, guys. The morning airline for Debjit, that's on the progress. So my first question is that so if I know, though decision were made on automatically the phase two person.

What did you still contain with allocation study automatically.

And what kind of that money to glean from that if it were discontinued.

You asked me a good questionnaire and obviously, we have a good level of comfort and Survivor program you seem to date early in the year as I said, we're going to be about two two could provide an update on the program. We feel good about program and a belief that that is an important data set to be generated.

Christian Martin Itin: So, we expect the same patients, but obviously, we're treating them in a slightly different setting than the inpatient setting. So, this is not a difference between the patients; it's a difference in the level of patient management required to actually get these patients safely through the therapy, and that is what the profile of Auto III is actually enabling us to expect.

Hmm, Okay. It are they planned for adaptation phases auto one as well.

At this point in time, there is no went to the reason for that is actually the the state the patients arrange themselves. So this is different from D.L.D.C.L.

Christian Martin Itin: And then with regard to the decision points, obviously, we're going to provide an update of where we are with the program at ASCO. That gives us a very good view of the response rate level. We will have additional follow-up that we'd like to see, which gets us slightly into the second half of the year, at which point we'll understand what the sustained CR rate looks like. And that will be the key piece of information that will inform us on the path forward. And as you can imagine, getting the data from the outpatient cohort would also enable us to actually design a pivotal study somewhat differently, including an outpatient setting in the pivotal study as well, which we believe would actually be a very important component of a pivotal program. So that data will be very informative in terms of the design of the study as well.

The the adult relapse your factory at the hotel patients typically are in in the end is very difficult situation. A lot of them are prone to step sees as a consequence of the disease progression up with the disease. So there are significant risk of picking up infections, a lot of them actually has to be managed.

In ice used for for sepsis and other types of court Morbidities.

On on as as a part of the normal course, all of the progression in L.C.N. stage of that disease. So the diseases quite different so in this setting you. We obviously will treat the patients mostly an impatient.

Setting for the first for the first few weeks just to have an ability to observe them a bee and and then it'd be able to map to help manage the disease, mostly a much less than a than syrupy itself. It is mostly that management disease eater.

Christian Martin Itin: Okay. Thank you. I appreciate it.

Christian Martin Itin: Thank you, Mara.

And <unk> think we're we're see a a large group of patients. We can then actually decide whether we might take a similar root does you know I was able to take with my previous program to map or we could do actually a a lot more of the activities outside the hospital at some point in time, but for this study the patient.

Christian Martin Itin: Your next question comes from the line of Debjit with HC Wainwright.

Christian Martin Itin: Hey guys, good morning. This is Aaron on behalf of DevJet.

Christian Martin Itin: Congratulations on the progress. So my first question is, so if a no-go decision were made on Auto 3, the phase 2 portion, would you still continue with the outpatient study of Auto 3? And what kind of learnings could you glean from that if it were discontinued?

Primarily treated in impatient setting.

Driven by the state that the patients or emotionally much list of them are actually the consequences of therapy itself.

Christian Martin Itin: You're asking a good question, Aaron. Obviously, we have a good level of confidence around the program. You saw the data early in the year. As I said, we're going to be able to provide an update on the program. We feel good about the program and believe that that is an important data set to be generated.

Okay. Thank you and then.

Okay.

Thank you.

That's it do you have another question.

<unk> yeah it.

One more in.

<unk>, comparing allogeneic and not politics Cartier approaches that do you think that the additional three to five week <unk> contribute to A.V.C.R.S. or neurotoxicity.

Christian Martin Itin: Okay, and are there any plans for an application size limit with Auto One as well?

Christian Martin Itin: At this point in time, there is no, and the reason for that is actually the state the patients are in themselves. So this is different from DL-BCL.

I don't think there is a a connection between.

<unk> time and.

Inside a kind of release of newer toxicity.

Christian Martin Itin: The adult, relapsed, refractory adult DLL patients are typically in a very difficult situation. A lot of them are prone to sepsis as a consequence of the disease and the progression of the disease. So they're at significant risk of picking up infections. A lot of them actually have to be managed in ICUs for sepsis and other types of comorbidities as a part of the normal course of the progression of the end stage of the disease. So the disease is quite different. So in this setting, we obviously will treat the patients mostly inpatient for the first few weeks, just to have the ability to observe them and be able to help manage the disease mostly, much less better than the therapy itself.

If you wouldn't have a concern around they too vain time or a long way too. Many times is that the disease may progressed further that look me more <unk> more tumolo typically means is often related to more adverse events. So if there's a connection that might be that there could be relationships. There. It's not what we're seeing it's not what we're pick.

[noise] Ah, but there is the the the the relationship you're suggesting I don't think it's there.

Oh great.

Okay. Thanks <unk>.

Yeah next question.

As far down.

Yeah, I guys. Congratulations all the progress and a initiation up your first pass at all.

Christian Martin Itin: It is mostly about managing the disease here. And obviously, as I think we see a larger group of patients, we can then actually decide whether we might take a similar route as I was able to take with my previous program, the Pulmonary Tumour Map, or we could do actually a lot more of the activities outside the hospital at some point in time. But for this study, the patients will be primarily treated in an inpatient setting, driven by the state that the patients are in mostly, much less so than actually the consequence of the therapy itself.

I guess first just on the list here go no go decision I should we expect that in concert with with Asheville in H.K. updates is that.

That mid year, and and I guess, the second part of it is just giving a strong positioning statement strong data we've seen so far in the commit.

Commitment to an outpatient study should we consider no go decision.

Unlikely and and you know would have to have something unusual happened between now and that decision. It just seems like it made a pretty strong positioning statement. The data seems very strong you're committing to or the development in an outpatient setting to just trying to understand that more than a timing and and and the bias towards go knogo.

Christian Martin Itin: Okay, thank you. Okay, bye. Thank you.

Christian Martin Itin: That's it. Do you have another question?

Right. So so obviously, we you know we're.

Christian Martin Itin: Yeah, I do. So, one more. In DLVCL, comparing allogeneic and autologous CAR T approaches, do you think that the additional three to five week vein-to-vein time could contribute to increased CRS or neurotoxicity?

Cannot guy due to the data where it back to present you know that's a few more weeks to go through that data.

As I indicated would feel good about the program that so what do you know so I picked up from the presentation I'm not a certainly true statement. So so this is where Ah well, obviously provide more update that ASKO, we'll have a bit more follow up in terms of the the time I think wanted to keep parameters that we're looking at <unk>.

Christian Martin Itin: I don't think there is a connection between Wayne-to-Wayne time and cytokine release and neurotoxicity. If you would have a concern around vein-to-vein time or long vein-to-vein times, it would mean that the disease may progress further. That would mean more tumor load, and more tumor load typically means more adverse events, so if there's a connection, that might mean there could be relationships there. It's not what we're seeing. It's not what we're picking up. But there is the relationship you're suggesting, I don't think there is.

<unk> and we're going to <unk> well enough. If you obviously for for ass scope of the belief that.

In the <unk> within the third quarter, we'll have I think the better visibility on on kind of the full day, just said from the patients we've treated to date in terms of the sustain see alright. So we'll get a very good view on that and that as you pointed out and then clearly.

Christian Martin Itin: Great. All right. Thank you.

Christian Martin Itin: Thank you, guys. Thanks, Christian. Thanks, Devjit. I appreciate it.

You know the fact that were want to move forward and actually explore the potential of the program in another patient setting is Oh say indicative also over all the publicity if you that we have a program.

Christian Martin Itin: Your next question- Hi guys, congratulations on all the progress and the initiation of your first pivotal. I guess first, just on the mid-year go-no-go decision: should we expect that in concert with ASCO and EHA updates? Is that mid-year? And I guess the second part of it is, just given the strong positioning statement, the strong data we've seen so far, and the commitment to an outpatient study, should we consider a no-go decision? It's unlikely and and you know would have to have something unusual happen between now and that decision. It just seems like you've made a pretty strong positioning statement. The data seems very strong, you're committing to further development in the outpatient setting, to just try to understand a bit more on the timing and and and and uh... the bias toward go no go.

And then Christian to the extent that when we get the update.

The upcoming medical meetings there'll be you know some need to make cross trial comparisons you feel like the baseline characteristics will hold up with yes guard out and that J. car 17, you know I I think back on when the debate between general one kite was on relative to burden.

So just maybe if you could give us a sense of tumor burden in whether you think it holds often will allow for those comparisons on a C.R. and durability of C.R.

I think the first of all you have some tumor burden I think you'll Philips present, the data on tour before it and as well and you'll see that this is a very comparable patient population I suppose reported <unk> and take her 17 them to have a burden in terms of kind of the patients that we have included I think we're tracking very nicely with the.

Christian Martin Itin: Right. So, obviously, I cannot guide you through the data we're about to present. There are a few more weeks to go for that data. As I indicated, we feel good about the program. That's what you also picked up from the presentation, and that is certainly a true statement. So, this is where we'll obviously provide more updates at ASCO. We'll have a bit more follow-up in terms of time. I think one of the key parameters that we're looking at is obviously sustained CR rates, and we'll have a view, obviously, for ASCO, but we believe that within the third quarter, we'll have, I think, better visibility on kind of the full dataset from the patients we've treated to date in terms of sustained CR rates. So, we'll get a very good view on that. And as you pointed out, clearly, the fact that we want to move forward and actually explore the potential of the program in an outpatient setting is obviously indicative of the overall positive view that we have of the program.

<unk> population there was always say the Undertaker 17 population it was somewhat different to what the just come with a population of all super closer to purchase Carter population of the J. car.

In general to Chase caught the population was it probably is a bit tougher population to deal with.

<unk>.

<unk>, maybe just a final question just on thoughts on outpatient treatment have you done much work talking to those 80% of centres that are treating patients away from tertiary care centres and what their threshold is to move.

Towards you know greater level of comfort with with car T., you always 100 patients data enough to kind of rule out the bad things in their minds and is there an in between scenario, where a strong profile could generate more referrals to church phrase shatters before.

Christian Martin Itin: And then Christian, to the extent that when we get the update at the upcoming medical meetings, there'll be, you know, some need to make cross-trial comparisons. Do you feel like the baseline characteristics will hold up with Yaskarta and JCAR-17? You know, I think back to when the debate between Juno and Kite was on relative tumor burden. So just maybe, you could give us a sense of tumor burden and whether you think it holds up and will allow for those comparisons on CR and durability of CR.

Communities actually pick up on it just trying to get a sense of level humpert and and your ability to to address that with with <unk> study.

It's a very good question and it it it's sort of any change in in sort of treatment paradigm or adoption is actually process that will take some time and it will require a buildup of confidence and and that is true. When you start with your your your K.L. else on the experience they make and then that's Elvis Shakespeare.

Christian Martin Itin: I think, first of all, yes, on Tumor Burden. I think you will also present the data on Tumor Burden as well, and you'll see that this is a very comparable patient population, as was reported for TSCARTA and JCR17 on Tumor Burden. In terms of the kind of patients that we have included, I think we're tracking very nicely with the TSCARTA population. There is obviously the JCR17 population, but it was somewhat different from what the TSCARTA population was. We're closer to the TSCARTA population than the JCR17. In general, the Chase Gardner population was probably a bit tougher to deal with.

For instance starts to propagate <unk>. So it's a process where you go where you we expect to go from.

The University hospital outpatient setting, which is one of the categories of outpatient to the on a non university hospitals outpatient setting and then you can actually move from there you have to expect that that will be sort of a gradual motion through the various types of centers.

And with that also you gain a lot of experience not just from a pivotal study, but then also from the ongoing experience going for it in terms of the real world.

Christian Martin Itin: Maybe just a final question on thoughts on outpatient treatment. Have you done much work talking to those 80% of centers that are treating patients away from tertiary care centers and what their threshold is to move towards a greater level of comfort with CAR-T? Is 100 patients' data enough to kind of rule out the bad things in their minds? Is there an in-between scenario where a strong profile could generate more referrals to tertiary centers before communities actually pick up on it? Just trying to get a sense of your level of comfort and your ability to address that with a pivotal study.

Continue to support the role item to capture hold out there all that opportunity in full.

All of these therapies, particularly new therapies take experience, which is personal experience with the with the product and that needs to be developed that needs to be rolled I'd appropriately.

Right. Thanks for taking the question than that congrats got on the progress.

<unk> much appreciate it.

In his question Kaufman line a barren.

<unk>.

Yeah, Hi, guys. Thanks for take my questions, maybe I could just start on the auto <unk> or.

Are you planning to those the opposition cohort with symbolism.

And then I guess on on that what are your thoughts in terms of of this data that we're I'm expecting soon mid year.

And should we be comparing these data to the most six data which represented at A.C.R. recently.

Christian Martin Itin: It's a very good question. Any change in treatment paradigm or adoption is actually a process that will take some time and will require a build-up of confidence. And that is true when you start with your KLLs and the experiences they have, and then that experience starts to propagate outwards. So it's a process where we expect to go from the university hospital outpatient setting, which is one of the categories of outpatient, to the non-university hospital's outpatient setting, and then you can actually move from there. You have to expect that that will be sort of a gradual motion through the various types of centers, and with that, obviously, you gain a lot of experience, not just from a pivotal study but also from the ongoing experience going forward in terms of the real-world data that will actually continue to support the rollout and the capture of that opportunity in full. All of these therapies, particularly new therapies, take experience, which is personal experience with the product, and that needs to be developed, and that needs to be rolled out appropriately.

Where I think they saw 46% C.R.A. and 75% or rate. So you know like I guess, if he could address those questions.

Yeah, Hi, there and thanks for joining obviously the way that we're treating the patients is that we're giving a single, though so <unk> and and that is going to be in any of the settings.

Obviously, the nice thing about this approach as you consider bake it into the Preconditioning regimen on which is a three day a regiment flew side regimen. So you can build it and and it can actually be nicely integrated in in any setting frankly.

With regards to to what we need to look at I think the.

Data you know using the P.D. alone monoclonal with just car if that didn't seem different.

In in any significant way from the Scarlet 890 absence of the P.D. alarm on a clone also I think we're just look at the <unk> data as it stands whether it's yeah. The original too much while Hello. This is my six trial I think they're there.

Christian Martin Itin: Great, thanks for taking the questions and congrats again on the progress.

Christian Martin Itin: Thanks a lot, Tim. It is much appreciated.

Christian Martin Itin: Your next question comes from a line by Byron Ann, which air... Yeah, hi, guys. Thanks for taking my questions. Maybe I could just start on the

Relatively close together and there's not an indication in I think that the edition of P.D., along monoclonal has increased or changed it profile.

Christian Martin Itin: and the Auto-3 Outpatient Cohort. Are you planning to dose the outpatient cohort with tembolizumab? And then, I guess on that, what are your thoughts in terms of this data that we're expecting soon, mid-year? And should we be comparing these data to the Zuma6 data which were presented at AACR recently? where I think

So it's going to be against it just Carter data as we as we know it today, which I think is is very consistent so that'll be comparing to what we're looking at them, but we this point clearly see.

The the most significant dataset does as we could tell from frequency perspective linguistics.

So so if humble isn't that doesn't provide any different contributions ethic of c.

Yeah, why not to evaluate the outpatient cohort without <unk>.

Christian Martin Itin: I think they saw a 46% CR rate and a 75% ORR rate.

I'm, sorry, that's not what I said, the I'm not sure what do you concluding.

Well I think also in the six.

Christian Martin Itin: So, you know...

<unk> if you look at US all kinetics, there was <unk> you know and when they showed us the data on some effects versus general wants all kinetic there wasn't really much of a change.

Christian Martin Itin: So, you know, I guess if you could address those questions. Yes, hi there, and thanks for joining me.

And one would have concluded that maybe you get better fanatics ends and the six because you have convalescent map on board.

Christian Martin Itin: Obviously, the way that we're treating the patients is that we're giving a single dose of Pembro on day minus one, and that will be in any setting. Obviously, the nice thing about this approach is you can sort of bake it into the preconditioning regimen, which is a three-day regimen, flu-cy regimen, so you can build it in, and it can actually be nicely integrated into any setting, frankly. With regard to what we need to look at, I think the data using the PD-L1 monoclonal with Chiskarta didn't seem different in any significant way from the Chiskarta data in the absence of the PD-L1 monoclonal. So I think we'll just look at the Chiskarta data as it stands, whether it's the original Zuma trial or the Sigma 6 trial. I think they're pretty good.

There wasn't Pembro on board was it <unk>.

But.

Well it has a sorry, but I mean <unk> pity one.

Yeah. It looks like it's an <unk> you know the interaction is not at the same place were acting on the T. on the T.C. I want the car T. So.

So acts on the on on the tumor. So so it's not necessarily the same biology to begin with you have different temporal has has additional impact on the t. cell itself.

So what we're seeing is obviously and this is what we're what would be talking about is is what will be looking at what sustains alright them, you'll start to get a view off that not the at the hospital presentation coming up and that's probably worthwhile, having a look at and as we go forward as indicated we will include pen grow as.

Part of the Preconditioning rent regimen, which was a single dose of Pembro, which obviously on its own doesn't have an impact on the lymphoma in in as I said as a as a an agent itself.

Christian Martin Itin: And there's not an indication, I think, that the addition of PD-L1 monoclonal antibody has increased or changed the profile. So it's going to be against the Chifcarta data as we know it today, which I think is very consistent. So that's what we'd be comparing to and what we're looking at. And what we, at this point, clearly is the most significant data set, as we can tell from an efficacy perspective in the space.

Okay, and then and then I guess this one one of the outpatient cohort what do you how I guess what are your plans for training the grade one to see our.

Are these patients gonna be truly outpatient like you know, we'll they'd be able to go home or are they going to be at a separate facility outside of the hospital.

Well that varies a lot depending on the institution typically if it is associated with a academic centers third those up basically you know Ah facilities relatively close by to the center.

Christian Martin Itin: So if Pembalizumab doesn't provide any additional contribution to efficacy... Yeah, why not evaluate the outpatient cohort without Pembroke?

That could be set up like a hotel as an example.

Where patients can actually you know be managed and obviously if need be they could be sort of you know looked at the end the context of the of the hospital itself. That's one set of settings. I mean is obviously the more distant settings, and you know going out and that's where all the snakes collecting the data on the feasibility on an empty experience.

Christian Martin Itin: I'm sorry, that's not what I said. I'm not sure what you're concluding.

Christian Martin Itin: I think the Zuma 6, if you look at the cell kinetics, there was really, you know, and when they showed us the data on Zuma 6 versus Zuma 1 cell kinetics, there

Christian Martin Itin: There isn't really much.

Christian Martin Itin: really much of a change, and one would have concluded that maybe you got better.

With it obviously, what do you want to make sure as you've captured the data what is the experience at the patient what is the safety profile what is the management requirements for these patients and that's what do you record.

Christian Martin Itin: Maybe you get better solokinetics with Enzyme VI because you have Pembrolizumab on board.

Christian Martin Itin: There wasn't Pembroke on board, was there? It was Atkinson.

And that's actually doesn't matter <unk> before that cool worked with or how far removed. The patient is whether patients as far removed from the hospital or not you know what do you need to do so you need to be able to collect the data. So most of what we're going to be working where are obviously centres that have outpatient facilities in in a reasonable distance to the sentence.

Christian Martin Itin: Um, but um... Well, at Tesla. Sorry. I mean, PD1. Yeah, the interaction is not at the same place. We're acting on the T cell, on the CAR T cell. A tezo acts on the tumor cell. So it's not necessarily the same biology to begin with. You have different, and tembro has an additional impact on the T cell itself. So what we're seeing is, obviously, and this is what we'll be talking about, is what we'll be looking at in the sustained CRH, and you'll start to get a view of that at the ASCO presentation coming up. And that's probably worth having a look at. And as we go forward, as indicated, we will include Pembro as part of the preconditioning regimen, which is a single dose of Pembro, which obviously on its own doesn't have any

Okay. That's helpful. Thank you.

Okay. Thank you very much.

Alright.

<unk> do anything any more questions.

Yeah next question costs and on line of met tell us what William player.

Okay. Thank you hi, guys. This is <unk> <unk> interesting questions.

Just just a very quickly on the or just only outpatient set and again.

<unk> your planning that if they are needed to new the whole study kind of entirely into the outpatient setting should not be you know should you make a decision on that one or <unk> discretion.

Christian Martin Itin: Okay, and then I guess just one more on the outpatient cohort. I guess, what are your plans for treating grade one to CRS?

Christian Martin Itin: Are these patients going to be truly outpatients, like, you know, will they be able to go home, or are they going to be at a separate facility?

Staking senses that and then maybe if I could just quit on all too or you know it's good to see some initial data <unk> the year that how how's enrollment being on on not Autosport City and you know maybe what can we expect.

Christian Martin Itin: They are in a separate facility outside of the hospital.

Christian Martin Itin: Well, that varies a lot depending on the institution. Typically, if it is associated with an academic center, those are basically, you know, facilities relatively close to the center. That could be set up like a hotel, as an example, where patients can actually, you know, be managed. And obviously, if need be, they could be sort of, you know, looked at in the context of the hospital itself. And that actually doesn't matter for that cohort, whether how far removed the patient is, whether a patient is far removed from the hospital or not. What you need to do is you need to be able to collect the data. So, most of what we're going to be working with are obviously centers that have outpatient facilities within a reasonable distance of the center.

<unk> at the end of the yet.

<unk>.

To make a decision on all took five and you know maybe possible via the outlook about program into 2020 on following on from from the data that are possible things.

Good thanks for joining a way the cards to the the the design of the pivotal study whether you want to make sure is that you have an ability to include centers that provide that treat patients in the outpatient segment as part of the pivotal study that was the idea to be able to do that so there will be a mix of patients that will be treated in an eight.

Patients and patients that are not in an outpatient setting but are you going to change the rate sufficient data that gives you then inability to move forward a waste abroad population and brought her treatment settings based on the data to generate in that study.

Christian Martin Itin: Okay, that's helpful. Thank you. Okay, thank you very much.

Christian Martin Itin: All right. Operator, do you have any more questions?

So that's the first part I'm. The first question. The second question related to older for old affordable somewhat impacted by the current covered into a situation and the the the challenges that we have to in terms of the.

Operator: Your next question comes from the line of Matt Phillips with William Blair.

Christian Martin Itin: Thank you. All right, guys. This is Rob. I'm on behalf of Matt here.

Christian Martin Itin: Thanks for taking the questions. Just a very quick one on the outpatient setting again, the additional cohort that you're planning there. Is the idea to move the pivotal study kind of entirely into the outpatient setting? Should that be, you know, should you make a good decision on that one?

Within the U.K., where we had obviously hospitals have to Chuck kinds of treatment for cancer patients that they were impacted we were not impacted with older three because we've basically could keep on operating in the U.S. at the same time, but <unk> all the forest predominantly operating as as as a clinical trial within the U.K.

Christian Martin Itin: Or is that still going to be kind of at the discretion of participating centers there? And then, maybe, if I could just give you a quick one on option four, you know; it was good to see some initial data at the start of the year there. How's enrollment been on that option four study? And, you know, maybe what can we expect in data at the end of the year? Is there likely to be enough to make a decision on option five? And, you know, maybe, if possible, a bit of an outlook for that program into 2021 following on from that data there, if possible. Thanks.

And therefore, we have been impacted we're in the process of evaluating what the impact is I think it's difficult to guide at this point in time bought level of impact who has a little guy probably made during the year once we have.

What we can expect a year and.

Great. Thanks very much.

Right. Thank you very much.

And ask questions on line of grant.

<unk>.

Good morning, or good afternoon. Thanks.

Questions and congratulate progress about three a question that.

You don't mind My first is.

And just focusing on the outpatient opportunity <unk> any sense that she could give us no. It's early days, but kind of what the incremental.

Christian Martin Itin: Hi Rob, thanks for joining us. With regard to the design of the Pivotal Study, what you want to make sure is that you have the ability to include centers that provide care for patients in the outpatient segment. As part of the Pivotal Study, that was the idea, to be able to do that. So there will be a mix of patients that will be treated in an inpatient setting and patients that are in an outpatient setting, but you want to generate sufficient data that gives you then an ability to move forward with the broader population and the broader treatment settings based on the data you generate in that study. So that's the first part and the first question.

Language revenue opportunities could be versus the annotation studying and then my second question, just what wanting to get an update on the allogeneic program Super interested in that and just keep it remind us how that program and how your engineering that you know the candidate.

How it might differ versus other a purchase from from other halogenate companies.

Christian Martin Itin: The second question related to Auto IV. Auto IV was somewhat impacted by the current COVID situation and the challenges that we had in terms of the UK, where hospitals had to shut down treatment for cancer patients, but they were impacted. We were not impacted with Auto III because we basically could keep on operating in the US at the same time, but Auto IV is predominantly operating as a clinical trial within the UK, and therefore we have been impacted. We're in the process of evaluating what the impact is. I think it's difficult to guide at this point in time what level of impact we'll have, and we'll probably guide it later in the year once we have better visibility of what we can expect by year end.

And and and lastly, I just want to touch upon a manufacturing I can just get us update on on where you on the manufacturing sides.

Capabilities of scale up and you know if there are any you know whatever the next key you know.

Internal milestones are looking for in terms of getting you know the company, where you think it needs to be thinking.

Hi, Greg Thanks for joining Oh say as a first starting with the auto three program at the question of course as terms of the impact on on on on market potential.

When you look at the centres of excellence impatient segments, which is where currently the car t. therapies are being used.

Christian Martin Itin: Great, thanks very much.

Christian Martin Itin: All right, thank you very much.

That is represents 10% of the actual commercial opportunity within the D.L.D.C.L. third lines are they going to U.S.

Christian Martin Itin: Your next question comes from the line of Gregg Slinovich with Goldman Sachs. Good morning or good afternoon.

So, but asking the question differently. If you you know terms with the increased over 90% of the market that there are you know we're looking to find a way to actually get tapped into there's an enormous opportunity ways substantially beyond the current.

Christian Martin Itin: Thanks for taking my questions and congrats on the progress. I've got three questions, if you don't mind. My first question is, Again, just focusing on the outpatient opportunity, any sense that you could give us, I know it's early days, but kind of what the incremental magnitude of the revenue opportunity could be versus the inpatient setting? And then my second question: I just wanted to get an update on the allogeneic program. I'm super interested in that.

How's that we're seeing other current opportunities to just sort of being visible from the car keys sales to do something because the literally catching up I tend to 11% of the total.

So that's I think hopefully gives a sense for the importance of of having a profile that allows you to go beyond the the incentive excellent impatient setting.

Christian Martin Itin: And if you could remind us how that program and how you're engineering the candidate might differ versus other approaches from other allogeneic companies. And then lastly, I just want to touch upon manufacturing. Could you just give us an update on where you are on the manufacturing side in terms of capabilities and scale up? And if there are any, what are the next key steps? Internal milestones you're looking for in terms of getting you know the company where you think it needs to be. Thank you.

Regards to the manufacturing question, obviously, we have been able and continue to manufacture throughout the peak of the coffee crisis.

I think which gives you on should give you a good sense have the ability that we're still going up now to be able to deliver including managing the complex supply chain of the U.S. with a vast reduction in commercial flights that would still feasible. So we feel good about it the way where we are on the commercials on the on the on the manufacturing site.

Christian Martin Itin: Hi, Greg, thanks for joining. I would say the first starting with the Auto III program and the question, of course, in terms of the impact on market potential. When you look at the Centers of Excellence inpatient segment, which is where currently the CAR T therapies are being used, That represents 10% of the actual commercial opportunity within the DLDCL third line setting in the U.S. So, asking the question differently, if you, you know, in terms of the increase, there are 90% of the market that are, you know, that we're looking to find a way to actually get tapped into, there's an enormous opportunity way substantially beyond the current profiles that we're seeing and the current opportunities that are sort of being visible from the car key sales that you're seeing, because they're literally catching about 10 to 11% of the, So that's, I think, hopefully gives a sense for the importance of having a profile that allows you to go beyond the center of excellence in patient settings.

I don't know her ability.

To deliver for our clinical studies, and obviously are now gearing up to to the full come talk to the pivotal study and that smell as other activities in the clinical scientists we've alluded to in the context of the presentation. So we're we're on track where we want to be with the <unk> with the manufacturing.

And have been able to consistently deliver product or even into currently mine, which certainly was a challenge for everyone in the business in our larger business I think for everyone that accompanies.

The final question was related to some of the technology that we started to show at the beginning of the year related to.

Inability to expand the technology into the towards the Alec Snake side, what we had shown at that point in time is programming module that renders to sales.

Christian Martin Itin: With regard to the manufacturing question, obviously, we have been able to manufacture throughout the peak of the COVID crisis. I think this gives you and should give you a good sense of the ability that we've developed now to be able to deliver, including managing the complex supply chain in the U.S. with a vast reduction in commercial flights, and that was still feasible. So we feel good about where we are on the manufacturing side and our ability to deliver for our clinical studies and, obviously, are now gearing up to the full conduct of the pivotal study and as well as other activities on the clinical side, as we've alluded to in the context of the presentation. So we're on track where we want to be with manufacturing and have been able to consistently deliver product even in the current environment, which certainly was a challenge for everyone in the business, in our larger business.

In a state where there's no t. cell receptors left on the surface actually your wife graft versus host disease, we'll do that with a in essence in capturing protein secretly pathway that captures the newly formed a piece of et cetera. So you can see complex isn't actually.

Shuttles them back to the E.R. for degradation that turns out to work very nicely and we show in a very nice set of graft versus host of these models.

Show the utility of that and a working whatever colleagues at the academic side to start up for this study towards the end of this year to first explore the utility off that module. So that's sort of where we are that program further elements of the technology, we haven't got discouraged.

Christian Martin Itin: The final question was related to some of the technology that we started to show at the beginning of the year related to an ability to expand the technology towards the allogeneic side. What we have shown at that point in time is a programming module that renders the cells in a state where there are no T cell receptors left on the surface, so you avoid graft-versus-host disease. We'll do that with, in essence, a capturing protein in the secretory pathway that captures the newly formed T cell receptor CD3 complexes and actually shuttles them back to the ER for degradation. That turns out to work very nicely, and we've shown, I think, a very nice set of graft-versus-host disease models that show the utility of that, and we're working with our colleagues on the academic side to start up a study towards the end of this year to first explore the utility of that module. So that's sort of where we are with that program; further elements of the technology we haven't yet disclosed.

And your final question crossing the line a single net.

Polygon global.

Just for the cool it seems like a really good up that I'm happy to add up.

Too quick questions.

And just give US a reminder.

Cost savings that treating patients is also three in and out <unk>.

Would bring.

Sort of the total cost of treatment <unk> to it's interesting to see most and it's going to be talking.

S D.C.T. yeah.

The presentation coming up with it.

<unk>.

About sort of some optimization techniques he's been using using say one product.

And I was just wondering you know so all the other.

Manufacturing tricks that can be.

<unk> brought in.

Christian Martin Itin: And your final question comes from the line of Samuel Leather with Polygon Global. Thank you very much for the call. It seems like a really good update, so I'm happy to hear that for sure.

The stage of development programs.

It seems that are very interesting, but I just wonder how much flexibility to the F.D.A., we'll give you changing manufacturing processes at this stage. Thanks.

Christian Martin Itin: Two quick questions. One, could you be really kind and just give us a reminder of, you know, sort of the approximate cost savings that treating patients, and also three, in an outpatient setting would bring? Again, sort of the total cost of treatment.

Thanks to anything sort of for joining I'll I'll start with the second question the.

In terms of the manufacturing processes, obviously, there's a a certain degree of of you know.

Christian Martin Itin: And two, it's interesting to see Martin Pooley is going to be talking at ASCCET, the presentation coming up on it, I think next week, about sort of some optimization techniques he's been using, using also one product. And I was just wondering, you know, sort of are there further manufacturing tweaks that can be brought in at this stage of development across the programs? You know, it seems sort of very interesting, but I just wonder how much flexibility the FDA will give you in changing manufacturing processes at this stage. Thanks a lot.

Proven to make that allow used to to stay within still the same product and you can do obviously quite a bit of work as you go through the early stages of development as you point that once you get into a into a pivotal study you obviously want to be sure that the process, you're running actually remains consistent throughout the trial so that indeed.

You have a proper integrity of the data set so to to that part of the question. You you don't want to move for change your manufacturing process in the pivotal study you want to actually keep it <unk> keep it steady and make sure that they're just a consistent data set.

Christian Martin Itin: Thanks, Dan, and thanks for joining us. I'll start with the second question. In terms of the manufacturing processes, obviously, there's a certain degree of, you know, improvements you can make that allow you to stay within the same product. And you can do, obviously, quite a bit of work as you go through the early stages of development, as you point out. Once you get into a pivotal study, you obviously want to be sure that the process you're running actually remains consistent throughout the trial so that, indeed, you have proper integrity of the data set. So to that part of the question, you don't want to move or change your manufacturing process during a pivotal study. You want to actually keep it steady and make sure that there is a consistent data set.

With regards to to in general process improvement in the in the end for car T. therapies, and very clearly lots of ways and how you over time can improve cos. It seems not to just similar to what we have seen you know and when we were developing kind of the from the early stages of antibody development to the kind of manufacturing processes do we have now a lot of that list.

You know continuous tweaking and optimizing individual processing steps and you know absolutely. Those are areas. There were very actively working on and and and looking for ways to continue to produce the process. He's going forward and I think that will continue to be an activity as you would have with any biological approach and certainly with that approach as as as complex and.

As much opportunity for for optimization as as a as a cellbased manufacturing process, but you're absolutely right. You don't want it rum changes three a pivotal study that would not be a good idea because it it risks the integrity of the study.

Christian Martin Itin: With regard to, in general, process improvement for CAR T therapies, very clearly lots of ways you can improve processes over time, not dissimilar to what we saw when we were developing from the early stages of antibody development to the kind of manufacturing processes we have now. A lot of that was continuous tweaking and optimizing of individual processing steps. Absolutely, those are areas we are very actively working on and looking for ways to continue to improve the processes going forward. I think that will continue to be an activity, as you would with any biological approach, and certainly with approaches as complex and with as much opportunity for optimization as a cell-based manufacturing process.

So that's the the first the the the second question. The first question you asked was about the costs related to the.

Management off the safety aspects in in it for the treatment of car T. patients.

The question, it's a very relevant one it's not that easy to quantify that precisely for each of the century city, but what we can say is that.

It's been a major issue within the U.S., Andrew staff that extra work that extra effort that has to be put into managed to patients put them in ice you et cetera.

Christian Martin Itin: But you are absolutely right. You do not want to run changes through a pivotal study. That would not be a good idea because it risks the integrity of the study. So that's the second question. The first question you asked was about the cost related to the management of the safety aspects of the treatment of CAR T patients, and the question is a very relevant one. It's not that easy to quantify that precisely for each of the centers.

It was not <unk>, he's not properly covered in the current reimbursement schemes and he's still not it was a problem early on and it continues to be a problem or the the amount of reimbursement at the hospitals can get for the management of the patients is still not sufficient which is certainly not only a an issue in terms of.

Resource use but in the hospital, but also he's a financial burden on on a lot on the hospitals on top and not remains a problem. Despite the fact that Oh said there is a certain level of compensation reimbursement that is built in in in in a in within the U.S., but it is not sufficient to cover the cost.

Christian Martin Itin: But what we can say is that it's been a major issue within U.S. centers that that extra work, that extra effort that had to be put in to manage the patients, put them in ICU, etc. is not properly covered in the current reimbursement schemes. And it's still not. It was a problem early on, and it continues to be a problem. The amount of reimbursement that hospitals can get for the management of patients is still not sufficient, which is certainly not only an issue in terms of resource use within the hospital but is also a financial burden on a lot of hospitals. And that remains a problem despite the fact that, obviously, there is a certain level of compensation or reimbursement that is built in within the U.S., but it is not sufficient to cover the cost. I don't think I can give you an exact number at this point in time, Dan, but I think the statement that, indeed, it is a loss-making operation for many of these centers is a true and remains a true statement.

I don't think I can give you an exact down but at this point in time and time down, but I think the statement that indeed, it is a a lossmaking operation from any of these Sanders is that true and remains a true statement.

Okay, that's very interesting.

To to find people were interested in doing the outpatient assessing.

Gang I'm fighting clinics.

I mean it is it it is obviously an interesting thing to do also because you know even if you run a an academic centers of excellence.

You know if you have a lot of resources behind find individual patient means that there is just left other patients you compare for so resource you Who's Who's also a challenge and it's an issue also with academic centers. So the the the interest is equally big whether this is on the impatient B.I. patience I to actually limit.

Christian Martin Itin: Okay, that's very interesting, and so has it been quite easy to find people who are interested in doing the outpatient setting in terms of going out and finding new clinics?

<unk> you might have resources that are needed to sort of manage a patient through and if you can then actually further relief that that burden by having the ability to actually move the patient either your normal boards that in addition, actually is easy to support than significant help for actually any of the centers.

Christian Martin Itin: I mean, it is obviously an interesting thing to do also because, you know, even if you're in an academic center of excellence, if you have a lot of resources bound by an individual patient, it means that there are just fewer other patients you can care for. So resource use is also a challenge, and it's an issue in academic centers. So the interest is equally big, whether this is on the inpatient or the outpatient side to actually limit the amount of resources that are needed to sort of manage the patient, and if you can then actually further relieve that burden by having an ability to actually move the patient out of your normal wards, that, in addition, is a support and significant help for any of the centers or practices.

Or or or practices.

Right. Okay. Thanks, again for much of a cool.

Okay. Thank you much appreciate it.

And then I thought the questions that this time.

Alright, well. Thank you very much at like to thank everyone for joining looking forward to obviously keeping updated through a very busy second set off the quarter with obviously a a a several calls to we're planning to update you on the data presentations at ask E.H.A.. The second part of the A.C. arm.

Christian Martin Itin: Okay, thanks again very much for the call.

But that I'd like to issue a great day, and looking forward to connecting with you and hopefully over the next few weeks. Thank you bye-bye.

Christian Martin Itin: Okay, thank you very much. I appreciate it.

Operator: And There are no further questions at this time.

Christian Martin Itin: All right, well, thank you very much. I'd like to thank everyone for joining us.

It's kind of close today's conference call. Thank you for your participation have a great Dane.

Operator: Looking forward to obviously keeping you updated through a very busy second half of the quarter with obviously several calls that we're planning to update you on the data presentations at ASCO EHA and the second part of the ACR meeting. With that, I'd like to wish you a great day and look forward to connecting with you obviously over the next few weeks. Thank you. This concludes today's conference call. Thank you.

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Operator: This concludes today's conference call. Thank you for your participation. Have a great day. © BF-WATCH TV 2021, ??? ??

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