Q4 2021 Autolus Therapeutics PLC Earnings Call

Yeah.

Okay.

Operator: Good day, and thank you for standing by, and welcome to Autolus Therapeutics' fourth quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode.

Good day, and thank you for standing by and welcome to Ottawa Therapeutics fourth quarter 2021 financial results Conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session.

Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised the call is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your host today, Lucinda Crabtree, Senior Vice President, Finance. You may begin. Thank you, Justin. Good morning or good afternoon, everyone.

To ask a question during the session you will need to press star one on your telephone.

Please be advised the call is being recorded if you require any further assistance. Please press star zero I would now like to hand, the conference over to your host today today.

No crowd G Senior Vice President Finance.

You may begin.

Yeah.

Lucinda Crabtree: And thank you for joining us to take part in today's call on the financial results and operational highlights for the fourth quarter of 2021. I am Lucinda Crabtree, Senior Vice President of Finance. With me today are Dr. Christian Itin, our Chief Executive Officer, and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during today's call, our discussion will contain forward-looking statements.

Thank you Justin good morning, or good afternoon, everyone and thank you for joining us to take policy today's call on the financial results and operational highlights for the fourth quarter 2021 .

And Cindy Crabtree senior Vice President of Finance.

Me today, a doctor you Christian Eitan, our Chief Executive Officer, and Andrew Oakley, Our Chief Financial Officer.

Lucinda Crabtree: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the section titled Risk Factors in our annual report on Form 20-F filed with the Securities and Exchange Commission on March 4, 2021, which can be accessed on the EDGAR database at www.sec.gov, and in subsequent filings we make with the SEC from time to time. The forward-looking statements on this call reflect the company's views as of today, March 10, 2022, regarding future events, and should not be relied upon as representing the speakers or the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some future point, the company specifically disclaims any obligation to do so, even if the company's views change.

Before we begin I would like to remind you that during today's call. Our discussion will contain forward looking statements.

All statements other than statements of historical facts on this cool all forward looking statements.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the section titled Risk factors in our annual report on form 20-F filed with the Securities and Exchange Commission on March 'twenty, 'twenty, one, which can be accessed through the Edgar database at Www Dot FCC.

You don't go and in subsequent filings, we make with the SEC from time to time.

The forward looking statements on this call reflect the company's views as of today March 10th 2022 regarding future events and should not be relied upon as representing the speakers' or the company's views as of any subsequent date.

The company May elect to update these forward looking statements at some future point the company specifically disclaims any obligation to do so even if the company's views change. These forward looking statements should not be relied upon as representing the company's views of any date subsequent to today.

Lucinda Crabtree: These forward-looking statements should not be relied upon as representing the company's views as of any date subsequent to today. TV advised that today's call is being reported and worked on. On slide three, you will see the agenda for today and it is as follows. Christian will provide an ODE of our operational highlights for quarter of 2021. Andrew will then discuss the country's financial results.

Be advised that today's call is being recorded on west coast.

On slide three you will see the agenda for today and it says Oh Golly Christian will provide an overview of our operational highlights the group core tier 121.

Lucinda Crabtree: Your Christian will conclude with upcoming milestones and any other concluding comments. Finally, we will, of course, welcome your questions following our Q&A session. All right, thank you very much, Lucy. And good morning, everybody.

Andrew will then discuss the Companys financial result, nickel Christian will conclude with upcoming milestones and any other concluding comments.

We will of course welcome your questions pulling out Vermont.

Thank you Christian.

Christian Itin: And thank you for joining us today. It's my pleasure to review our operating progress for the fourth quarter of 2021. If we move to slide number five, I'd like to give you a run through of the key operational updates from 2021. First of all, our multicenter FELIX study for our lead product, OBCell, is going well, and we're making good progress in our mission of building a leading acute lymphoblastic leukemia company. We're expecting data from the FELIX study in the second half of the year, with full data in the first half of 2023.

Alright, Thank you very much Lucy and good morning, everybody and thank you for joining US today, It's my pleasure to review our operating progress through the fourth quarter 2021, if we move to slide number five I'd like to give you a run through of the key operational updates from 'twenty to 'twenty. One first of all our multicenter <unk> study for our lead product <unk>.

Going well and we're making good progress in our mission of building, a leading acute lymphoblastic leukemia company.

We're expecting data from the field study in the second half of the year with full data in the first half of 2023.

Christian Itin: The program is not only designed for the treatment of acute leukemia, but also has the potential applications in the broader set of Non-Hodgkin's lymphoma indications, and has shown a consistent and best-in-class efficacy and safety profile across three BALL Phase I studies in patients with a wide range of age, disease burden, and prior therapy. In November 2021, we were pleased to announce a strategic collaboration and financing agreement with Blackstone Life Sciences, who have committed to invest up to $250 million into the development of OBCell in adult ALL, supporting the full development of the program towards commercialization, with $150 million already having been received in the shape of equity and project financing.

The program is not only designed for the treatment of acute leukemia, but also has the potential applications in the broader set of non Hodgkin's lymphoma indications and has shown a consistent and best in class efficacy and safety profile across three P. A L. L phase one studies in patients with a wide range of age disease burden on prior therapies.

November 2021, but we're pleased to announce a strategic collaboration and financing agreement with Blackstone Life Sciences, we have committed to invest up to $250 million into the development of <unk> in adult day on the Hill supporting the full development of the program towards commercialization with $150 million already having been received into shape.

As equity and project financing.

Christian Itin: In September, we received planning approval for our new manufacturing facility in Stephenage, UK. This 70,000 square foot facility will be leased to Autolus and is another important step for us on our journey to becoming a fully integrated commercial company. The facility will have an initial capacity of approximately 2,000 GMP batches per year, with further scope to expand.

In September we received a planning approval for our new manufacturing facility in Stevenage U K. This 70000 square foot facility will be leased to art listen there is another important step for us on our journey to becoming a fully integrated commercial company.

The facility will have an initial capacity of approximately 2000 GMP batches per year with further scope to expand this capacity will support the launch of Ob Sal and secure global supply A&D initial indications we will go into this in more detail later in the presentation.

Christian Itin: This capacity will support the launch of OBCell and secure global supply in the initial indication. We will go into this in more detail later in the presentation. During the course of the year, we expanded our board with two significant appointments. Firstly, we were delighted to announce the appointment of John Johnson as non-executive chairman.

During the course of the year, we expanded our board with two significant appointments. Firstly, we were delighted to announce the appointment of John Johnson as Nonexecutive Chairman John has brought a wealth of commercial oncology and business experience to auto list and is a recognized leader in the biopharmaceutical industry, having held a number of executives operational and commercial leaders.

Christian Itin: John has brought a wealth of commercial oncology and business experience to Autolus and is a recognized leader in the biopharmaceutical industry, having held a number of executive, operational, and commercial leadership roles. His experience is proving invaluable as we look towards the commercial launch of what we sell. Secondly, in conjunction with the Blackstone collaboration, Dr. William Young joined Autolus as a non-executive director.

Chip rolls.

Spirit is proving invaluable as we look towards the commercial launch of what we sell secondly in conjunction with Blackstone collaboration Dr. William Young joined <unk> as a nonexecutive director Bill is one of the pioneers of our industry and brings a wealth of commercial and operational experience to all of this at a time when we're shaping the product profile and the.

Christian Itin: Bill is one of the pioneers of our industry and brings a wealth of commercial and operational experience to Autolus at a time when we're shaping the product profile and the commercial strategy of OBC. In terms of other updates, Andrew Oakley is retiring from his role as CFO with Lucinda Crapptree who has worked in a number of roles at Autolus, taking over from him on the 30th of March this year. I look forward to working with Lucien or expanded role and would also like to thank Andrew for his many contributions to Autolus over the years. At least a company in a strong position and I wish him much happiness in the next chapter of his career.

Commercial strategy, although we sell.

In terms of other updates Andrew Oakley is retiring from his role as CFO with Lucinda Crabtree, who has worked in a number of roles at artless, taking over from him on the 31st of March This year I look forward to working with Lucien her expanded role and would also like to thank Andrew for his many contributions to <unk> over the years at least the company in.

Our strong position and I wish him much happiness in the next chapter of his career.

Christian Itin: Moving on to slide six. This is just a reminder of the terms of the collaboration with Blackstone. It has strengthened our balance sheet and, as I've already mentioned, will allow us to drive the OB-cell program and build up the commercial manufacturing capacity. Importantly, assuming all the milestones are received, this collaboration supports a catch runway into 2024. With that, let's switch gears and move on to slide number seven.

Moving on to slide six this is just a reminder of the terms of the collaboration with Blackstone.

Strengthened our balance sheet and as I've already mentioned will allow us to drive the Ob cell program and build up the commercial manufacturing capacity importantly, assuming all of the milestones are received this collaboration supports a cash runway into 2024.

With that lets switch gears and move on to slide number seven.

Christian Itin: 2021 was a busy year as far as driving our programs and clinical updates were concerned, and I'd like to give you a summary of the key program updates. OBSEL is on track to be the first Autolus product candidate tested in a pivotal study. As you remember, our key focus is on delivering the Felix study in adult patients with relapsed refractory acute limbalastic leukemia, where the study enrolling patients are both post-clinatumap or inatuse amap treatment, as well as patients that are just progressing in a rehab setting but may not have received yet inatuse amap or plinatumap.

2021 was a busy year as far as driving our programs and clinical updates were concerned and I'd like to give you a summary of the key program updates Ob.

<unk> is on track to be the first almost product candidates are tested in a pivotal study as you remember our key focus is on delivering the Felix study in adult patients with relapsed refractory acute lymphoblastic leukemia with the study enrolling patients who are both post splinter to them at or in a twosome have treatment as well as patients that are just progressing in a very upsetting.

But may not have received yet introduce a map for cleaner to them at the.

Christian Itin: The initial FELIX Phase 1b study presented at ASH in December 2021 showed a favorable safety and efficacy profile consistent with the Olcar-19 study in this patient population. Furthermore, as we presented in December, the duration of response from the Olcar-19 study remains highly encouraging, with morphological event-free survival for OB cell of 46% at 24 months of follow-up, with a median follow-up of 29.3 months, and patients approaching up to 42 months of durability.

The initial Felix Phase one B study presented at Ash in December 2021 showed a favorable safety and efficacy profile consistent with the old car 19 study in this patient population. Furthermore, as we presented in December the duration of response from the old car 19 study remains highly encouraging with morphologic.

<unk> event free survival for Ob sale of 46% at 24 months of follow up with a median follow up of 29 points 29.3 months and patients approaching up to 42 months of durability.

Christian Itin: We continue to see sustained ovocell persistence in those patients as well. As I mentioned earlier, we're also exploring the activity of OB cell beyond ALL in the context of the old car-19 extension study and the data presented at ash demonstrated a favorable safety profile with 13 of 13 non-hot conflict formal patients achieving complete metabolic remission. It is also important to mention the long-term persistence of OBCell demonstrated by quantitative PCR in this patient group.

We continued to see sustained ob cell persistence in those patients as well.

As I mentioned earlier, we're also exploring the activity of Ob sell beyond ALLL in the context of the old car 19 extension study and the data presented at Ash demonstrated a favorable safety profile with 13 of 13, non Hodgkin's lymphoma patients achieving complete metabolic relation.

It is also important to mention the long term persistence of Ob sell demonstrated by quantitative PCR in this patient group.

Christian Itin: We're planning additional updates from the All-CAR Extension Study at the European Hematology Association meeting in June 2022. In addition to OBCell development, we're working on a next generation product candidate which forms part of our lifecycle management strategy. For this candidate, we've added a highly potent CD22 car on top of the CD19 car that is the foundation for the OBCell program. This new program, called OTTA 122, is currently being evaluated in pediatric patients in the CARPAL Extension study.

We're planning additional updates from the old car extension study at the European Hematology Association meeting in June 2022, and.

In addition to Ob shell development, we're working on the next generation product candidates, which forms part of our lifecycle management strategy for this candidate we've added a highly potent CD 22 car on top of the CD 19 car that is the foundation for the obesity program.

This new program called Autobahn 'twenty two is currently being evaluated in pediatric patients in the car patent extension study, we plan to share additional clinical data on this product.

At <unk> in June finally, our program order for in peripheral T cell lymphoma has made good progress and where it moved through the dose escalation. We plan to present initial clinical data from the dose escalation trial at DHA in June as well.

Christian Itin: We plan to share additional clinical data on this product, at EHA in June. Finally, our Program Auto IV in Peripheral T-cell Lymphoma has made good progress and we're moved through the dose escalation. We plan to present initial clinical data from that dose escalation trial at EHA in June as well. Moving to slide number nine. Focusing specifically on adult acute lymphoplastic leukemia, there is a very high unmet medical need for these patients, ALL is a very challenging disease. It resides in the bone marrow, and it is formed and driven by cells that are very close to actual stem cells.

Moving to slide number nine.

Focusing specifically on adult acute lymphoblastic leukemia, there is a very high unmet medical need for these patients <unk> is a very challenging disease. It resides in the bone marrow and it is forum and driven by sales that are very close to actual stem cells those.

Christian Itin: Those cells have enormous proliferative potential, and they're very challenging to manage. Because they reside in the marrow and crowd out normal marrow cells, patients tend to become significantly immune suppressed as a consequence of the disease itself. The standard of care that we're using in this space is high-dose combination chemotherapies, which consists of intervals of treatment with short recovery times that are done and repeated in cycles. It is a horrendous type of treatment for patients to go through.

And those sales have enormous proliferative potential and theyre very challenging to manage.

Because they reside in the marilu and crowd at normal marrow cells, the patients tend to become significantly immune suppressed as a consequence of the disease itself.

Standard of care that we're using in this space is high dose combination chemotherapies, which consists of intervals of treatment with short recovery times that are.

Done and repeated in cycles.

Is horrendous type of treatment for patients to go through the outcome. However, it's positive from a response perspective about 90% of the patients achieved complete remission. The challenge. However is that most of these permissions are short lift and the patients relapse in fact, only about 30% of the patients see longer term benefit after the initial line of therapy.

Christian Itin: The outcome, however, is positive from a response perspective. About 90% of the patients achieve complete remission. The challenge, however, is that most of these remissions are short-lived and the patients relapse. In fact, only about 30% of the patients see longer-term benefits after the initial line of therapy. Once you relapse, the outlook is rather poor. The disease tends to progress rapidly. I've lost the signal.

Once you relapse the outlook as well the poor the disease tends to progress rapidly.

I've lost the signal.

Christian Itin: [inaudible] Pardon, Andrew? Yes. Oh, I'm sorry. Have we lost Christian? Yes, I think we have, I can't tell you him.

Pardon Andrew.

Yes.

Oh I'm sorry.

We lost Christian.

Yes, we have a control.

Christian Itin: Okay, I'll continue. So, we were on slide. Slide 9. So Christian just said that disease tends to progress rapidly. A normal course of action is that these patients have the option of a set of targeted therapies which include Blimps Cyta, Vesponsa, and Tercatus with or without a stem cell transplant. Overall, the challenge has been with these patients that they are prone to have immunological toxicities, particularly if you use immune-based therapeutic approaches like Brunstein or Kekati.

All right I'll continue.

So we were on slide.

Slide nine.

So Christian Brian said, the disease tends to progress rapidly.

Course of action is that these patients have the option of a set of targeted therapies, which include Lynch, Georgia.

So kicked conscious waste oversell the stem cell transplant.

Overall, the challenge has been with these patients they are prone to have immunological toxicities, particularly if you use immune based therapeutic approaches slips and slides for CIT conscious.

Christian Itin: These patients are rather fragile and have a lot of co-morbidities. You need to have a therapeutic approach that is, on the one hand, highly potent, but, on the other hand, well tolerated. That's quite a tall order to combine these different set of properties into a single product.

These patients throughout the fragile and had a lot of Comorbidities you need to have a therapeutic approach that is on the one hand highly potent but on the other hand well tolerated.

That's quite a tall order to combine these different set of properties.

Single product.

Christian Itin: We believe that is exactly what we're doing with OB-SYN. Obacil has received orphan drug designations as well as designations for accelerated reviews with various regulators. So if we can move on to slide 10. Here is a quick summary of the three products that have been more recently have been approved. All are targeted therapies. Blimcyto, targeting CD19, Inzotrimumab, targeting CD22, and Ticartis, a CD19 kind.

We believe that is exactly what we're doing with Ob. So.

<unk> received orphan drug designations as well as designations for accelerated reviews with various regulators.

So if we can move on to slide 10.

Yeah.

Here's a quick summary of the three products that have been more more recently been approved all targeted therapies targeting.

Targeting CD 19 instrument targeting CD 22, and conscious of CD 19 car.

Christian Itin: What we're seeing with all of these products is a high degree of activity in terms of complete remission rates that can be achieved at a range between the 40s up to the 80% range. However, the fundamental challenge has been, with all these therapies, to get sustained responses, and that still remains elusive. As you see in the table, if we're looking at 18 months of event-free survival, those numbers are relatively low. They're about 10% for Brunsaita, which is the market-leading product, and they go up to about 25% for TecCast. The toxicities that we're seeing with these agents are typically immunological toxicities and with intratumor meb also hepatic toxicities. Lincito and Ticardis trigger cytokine release syndrome and neurotoxicity.

What we're seeing with all of these products is a high degree of activity in terms of complete remission rates that can be achieved at a range of between 40 <unk> up to the 80% range.

However, the fundamental challenge has been with old based therapies to get sustained responses and that's.

Still remains elusive.

As you've seen the table if we're looking at 18 months of event free survival. Those numbers are relatively low there are about 10% from <unk>, which is the market leading product. They go up to about 25% subject classes.

The toxicities that we're seeing with these agents are typically immunological toxicities with <unk>.

<unk> also hepatic toxicities.

Sorry to interrupt.

So let it go and released syndrome neurotoxicity.

Christian Itin: However, the products differ in the severity of those toxicities, with BlinCytos showing low levels, where Tercatus showed elevated levels of Severe, CRS, and IQ, with Ticadas about 25% of the patient's experience, high grade CRS, and 35% of the patient's experience, high grade neurotoxicity. So if we move to slide 11. Ovocell is a unique mechanism of action. It is designed to efficiently engage leukemic cells without remaining bound to the leukemic cell after the kill has been delivered.

Well the product is different and the severity of those toxicities between sort of showing low levels, which should elevated levels of severe Crs and my kids.

With the account is about 25% of the patients experience high grade Crs and 35% of the patients experience high grade neurotoxicity.

So if we move to slide 11.

<unk> has a unique mechanism of action and its.

Designed to efficiently engage leukemic cells without remaining bound leukemic cell. After the kiln is been to visit.

Christian Itin: This feature is important to minimise Side-A-Con release. Avoid T-cell exhaustion, maximize T-cell expansion and the systems and thus maximize anti-liquimic activity while minimizing side effects. The key technical feature driving these desirable properties is a binder to CD19 on the tip of the chimeric antigen receptor that has a fast on-rate combined with a fast off-rate. And as illustrated on this slide, the on-rate of OBCell is comparable to Kymriah. However, the off-rate is approximately 100 times faster.

This feature is important to minimize cytokine release.

T cell exhaustion maximize T cell expansion and persistence.

Maximize anti leukemic activity, while minimizing side effects.

Christian Itin: This translates into a big difference in the time the receptor is bound to CD19. So if we move to slide 12. We've had the opportunity to evaluate OBSEL at this point in three phase one clinical trials. They cover quite a range of patients in ALL. We started with the program in pediatric patients, moving then to an adult patient population that we treated in the UK, and then the Phase 1b run-in for the pivotal study where most of the patients were recruited in the U.S. What we see across these three phase one studies is a very consistent outcome.

Technical feature driving these desirable properties is appointed to CD 19 on the tip of the chimeric antigen receptor that has financed on rate combined with a <unk> offering.

And as illustrated on this slide you on rate of obesity is comparable to Kim Ryan.

The off rate is approximately 100 times faster.

This translates into a big difference in the time the receptor is bound to CD 19.

So if we move to slide 12.

We've had the opportunity to evaluate that'd be sold at this point in three phase one clinical trials.

But quite a range of patients.

We started with the program in pediatric patients.

Moving then to an adult patient population that we treated in the U K.

And then the phase one be running for the pivotal study with most of the patients were recruited in the U S.

What we see across these three phase one studies is a very consistent outcome.

Christian Itin: None of the patients that we have treated in these studies, which is a total of 50 patients so far, have experienced any form of high-grade, Cytokine Release Syndrome, They also experienced only limited high-grade neurotoxicity, and that was a rapidly reversible, with a steroid, intervention. [inaudible] as you can see in the adult population. Whereby, we look at any green line for neurotoxicity. It is fairly low.

None of the patients that we've treated in these studies, which is a total of 50 patients. So far have exchanged any form of high grade cytokine release syndrome.

But you also experienced only limited high grade neurotoxicity.

And that was rapidly reversible with steroids intervention.

As you can see in the adult population.

Christian Itin: It's between 13 and 20 percent far off from the close to 90 percent that we're seeing with the currently approved product in the space. [inaudible] We're seeing this consistent outcome despite a difference in the underlying patient conditions that we have in these trials, starting with the children with a median age of nine years, going to adults with a median age of 42 years, and a wide range of tumor burden, going from 21% of patients with high tumor burden to 75% of patients with high tumor burden, and also a varying degree of pretreatment with Benzaito. What is very encouraging is the fact that the data is highly consistent across this wide range in these patient populations. So if we turn to slide 13, please.

Whereby we'd look at any great line of neurotoxicity is fairly low.

Between Celgene and 20% firewall from the close to 90% that we're seeing with the currently approved product in the space.

We're seeing this consistent outcome. Despite the difference in the underlying patient conditions that we have in these trials starting with the children with a median age of nine years going to adults with a median age of 42 years and a wide range of tumor burden going from 21% of pace.

<unk> with high tumor burden to 75% of the patient a patient with Tony Chambers.

And also a varying degree of pre treatment with <unk>.

So anytime.

What is very encouraging is the fact that.

The data is highly consistent across this wide range and this patient in these patient populations.

So if we turn to slide 13 please.

Christian Itin: So just, if you look at the data from the all-car-19 study [inaudible] What we've been able to show is that we have exceptional persistence. And there's very similar data that we could show and have published in the Pediatric Health Health Study. What you see on the left-hand side here is the median persistence of the county cells; now look up to a time point of 24 months of follow-up. What is important is that this is not just a faint signal that you pick up by genetic marking.

So just if we look at the data from the old come 19 study.

What we've been able to show is that we have exceptional persistence and there's very similar data that we could show that have published on the pediatric study.

What you see on the left hand side here is the median persistence of the car T cells.

Now I'll look up to a time point of 24 months of follow up.

What is important is that this is not just a signal that you could pick up a bunch of making marking.

Christian Itin: This is looking at cells in circulation using flow cytometry analysis to determine the presence of CAR T cells. These CAR-T cells are active, so we see continued B cell aplasia in these patients as well. What that translates to is what you see on the right-hand side.

This is looking at cells in circulation using flow cytometry analysis to determine the presence of car T cells.

These car T cells active so we see continued bisso aplasia in these patients as well.

What that translates to is what you see on the right hand side on the right hand side you see the event free survival of these patients looking at patients in ongoing complete remission.

Christian Itin: On the right-hand side, you see the event-free survival of these patients, looking at patients in ongoing, complete remission. As the patients reach 12 months of follow-up, the event-free survival stabilizes at around 46% and stays flat up to two years and out to three years. In other words, we've been able to get these patients who have initial relapses to then stabilize. The patients that made it beyond 12 months have stayed in complete remission.

As the patient reached 12 months of follow up the event free survival stabilizes at around 46% and stays flat up to two years and up to three years.

In other words, we've been able to get these patients who at initial relapses today and stabilize.

The patients that made it beyond 12 months have stayed in complete remission.

Christian Itin: That is very encouraging and very different. Remember, I highlighted before that Lensito 18 months EFS is at 10%, and Ticatus 18 months EFS is at about 25%, and we're at 46%, and we continue to stay there.

That is very encouraging and very different remember I highlighted before.

Then slide 18 months PFS is at 10% and to countless 18 months PFS is at about 25% and we're at 46% and we continued to stay there, whereas all of them currently.

Christian Itin: The approved programs continue to deteriorate. The approved programs continue to deteriorate. The approved programs continue to deteriorate. Andrew, I'll stop you there.

The approved programs continue to deteriorate.

Operator: I think Christian's back with us to turn to slide 14. Oh, very good. Very good. Thank you very much, Andrew. And apologies, everybody, for dropping off the line here. But I hope it's going to hold for now.

Andrew I'll stop you there I think Christian is back with us to turn to slide 14, well very good.

Very good thank you very much Andrew and apologies everybody for dropping off the line here.

Christian Itin: So moving to slide 14. In summary, we believe that the profile of the product has the potential to be transformational for adult patients. We're building on a unique mechanism of action with a very high level of complete remission rate that shows and translates with excellent persistence into long-term event-free survival in these patients, and now with a median follow-up of close to 30 months from the old-car study. We combine this very favorable profile with a very favorable safety profile with no high-grade cytokine release syndrome and very limited neurotoxicity.

I hope, it's going to hold for us.

So moving to slide 14.

Some really believes that the profile of the product has the potential to be transformational for adult patients were building on a unique mechanism of action with a very high level of complete remission rate that shows and translates with excellent persistence into long term event free survival in these patients and now with the median follow up of close to 30 months from BMO.

Car study, we combined this very favorable profile with a very favorable safety profile with no high grade cytokine release syndrome, and very limited neurotoxicity.

Christian Itin: Turning to slide 15, we're conducting a pivotal study at this point in time. It's a 100-patient, single-arm study. We expect to be fully enrolled as we go through the course of this year and expect to have initial data starting in the second half of this year with full data in the first half of 2025. Moving to slide 16. I'd like to take a few minutes to take a quick look at the market as it currently presents itself. For hematological malignancies, CAR T-cell delivery is fast becoming established care and has nearly doubled in 2021.

Turning to slide 15, we're conducting a pivotal study at this point in time, it's a 100 patient single arm study, we expect to be fully enrolled as we go through the course of this year and expect to have initial data starting in the second half of this year with full data in the first half of 2023.

Moving to slide 16.

I'd like to take a few minutes to take a quick look at the market as it currently presents itself for Hematological malignancies car T cell delivery is fast becoming established care and has nearly doubled in 2021 car.

Christian Itin: CAR T-cell therapy has had notable success in moving to earlier lines, noting the BLBCL second line studies, ZUMO 7 and TRANSFORM, which will accelerate adoption and expansion of treatment centers. If we look specifically at ALL, redirected T-cell engagement in the form of Lincyto has become standard of care. You can see the product has been doing well and is continually adding market share. We estimate that over 2,000 adult patients currently receive Lincyto, and it continues to grow at a healthy rate at around 25%, as it is benefiting both from a broader delivery footprint and moving to earlier lines in therapy. As context though, the CAR T price that we have between the various approved products range from about $400,000 to just shy of $500,000 in the current environment.

Car T cell therapy has had notable success in moving to earlier lines, noting the Bcl second line studies, Zuma, seven and transform which will accelerate adoption and expansion of treatment centers. If we look specifically at Anl redirected T cell engagement in the <unk> side, who has become standard of care you can see.

The product has been doing well and is continually.

Adding market share we estimate that over two thirds of adult patients currently receive <unk> and it continues to grow at a healthy rate at around 25% as it is benefiting both from a broader delivery footprint and moving to earlier lines in therapy.

As context, though the car T price that we have between the various approved products range from about 400000 to just shy of $500000 in the current environment.

Christian Itin: I would note that our Felix study protocol permits prior Blinna use, as we do not view Blinna as a direct competitor per se, as treatment can be sequenced. More than likely, Descartes will be the main competitor to Obacel, as it will be the only Cartesil product on market, so will have established the use in adult ALL. To remind, Descartes is now approved by the FDA for adult ALL, with other countries set to follow later this year.

I would note that our Felix study protocol from its prior planar used as we do not view blayne as a direct competitive per se.

As treatment can be sequenced.

More than likely to Carlos will be the main competitive Toby sell as it will be the only car T cell product on market. So we will have established.

We'll have established for use in adult AML to remind to Carlos is not approved by the FDA for adult AML with other countries set to follow later this year.

Christian Itin: We believe that OBCell has curative potential as a stand-alone product and is poised to be best-in-class product for this indication, and OBCell, we believe, is also poised to benefit from the other trends that we've discussed, expansion of the delivery footprint, both from a number of centers, giving CAR-T cell therapy, and use in ambulatory setting and in outpatient therapy, moving CAR-T cell therapy into earlier treatment paradigms. Switching gears to slide 17.

Adobe cell has curative potential as a standalone product and is poised to be best in class and best in class product for this indication Adobe cell. We believe is also poised to benefit from the other trends that we've discussed this expansion of delivery footprint both from number of centers.

Given car T cell therapy, and use an ambulatory setting as an outpatient therapy and moving car T cell therapy into earlier treatment paradigms.

Switching gears to slide 17.

Christian Itin: The manufacturing of cell therapies is complex and requires a great deal of skill and experience. As we mentioned earlier, in September 2021, we announced that planning approval has been granted to build the company's new manufacturing facility in Stevenage IV in the UK. This location is about a mile from our current clinical manufacturing operations at the CGT facility and will allow us to transition our entire operation, experience, staff and operations to the new facility, which will minimize startup risks and costs for commercial supply.

The manufacturing of cell therapies is complex and requires a great deal of skill and experience as we mentioned earlier in September 2021, we announced that planning approval has been granted to build the company's new manufacturing facility in Stevenage four in the UK. This.

This location is about a mile from our current clinical manufacturing operations at the CGT facility and will allow us to transition our entire operation experienced staff and operations to the new facility, which will minimize startup risks and costs for commercial supply.

Christian Itin: As we have worked out for the supply of our pivotal study with centers across the U.S. and Europe, the Caucasian is well suited for global supply with easy access to several international airports, including London Heathrow. The 70,000-square-foot facility is being leased to Autolus and will allow for approximately 2,000 batches a year of initial capacity, with scope to expand further when needed.

As we have worked out for the supply of our pivotal study with centers across the U S. Europe . The cocaine is well suited for global supply with easy access to several international airports, including lung disease trials.

The 70000 foot square foot facility is being leased to Atlas and will allow for approximately 2000 batches of year of initial capacity with scope to expand further when needed you will see below an image of what the facilities should look like once completed and also on the right side of snapshots of the works on the way in the middle of February .

Christian Itin: You will see below an image of what the facility should look like once completed, and also on the right side a snapshot of the works underway in the middle of February. Facilities are scheduled to support licensure submissions for OVCEL in 2023, as well as to begin supporting clinical manufacturing supply in the second half of 2023, as well, upon MHRA authorization. Moving to slide 18, as I indicated, we're also evaluating the products outside of ALL in non-Hodgkin's indications, and expect to provide updates on these programs over the course of this year. Moving to slide 20.

The facility is on schedule to support license their submissions for Ob said on 2023 as well as to begin supporting clinical manufacturing supply in the second half of 'twenty as well a palm MH already authorization.

Moving to slide 18, as I indicated we're also evaluating the products out.

Outside of AML, and non hodgkins indications and expect to provide updates on these programs over the course of this year moved.

Moving to slide 20.

Christian Itin: We started exploring OBSL in BNHL indications and also CLL last year. In the 16 patients we have reported so far, we've seen a remarkably positive safety profile with no high-grade cytokanvalese syndrome and no patient experiencing any form of neuro toxicity. [inaudible] Moving to slide 21, as we've seen in ALL, in BNHL, we see excellent expansion and engraftment. The CAR T cells behave very similar to what we've seen in the ALL patients.

We started exploring oversell A&P NHL indications and also CLS last year and.

In the fixings patients who have reported so far we've seen a remarkably positive safety profile with no high grade cytokine release syndrome at no patient experiencing any form of neurotoxicity.

Moving to slide 21, as we've seen in ALLL NBA NHL, we see excellent expansion any grasp the car T cells behave very similar to what we've seen in the AML patients.

Christian Itin: Flight 22, then, shows the results that we actually have very high levels of clinical activity. All non-hersicum inflammation patients achieved a complete metabolic remission, and that gives us obviously a strong basis to build on. We had one CLL patient in addition to the non-hersicum patients that had a partial response with minimal residual disease, a negative condition in the bone, all in all. The results are obviously very encouraging. Furthermore, as you can see, we have initial good durability in the follicular patient.

Slide 22, then shows the results.

Half shows results that we actually have very high levels of clinical activity.

All non Hodgkin's lymphoma patients achieved a metabolic complete remission.

And that gives us obviously a strong.

<unk> to be able to all we had one CLO patients. In addition to the non Hodgkin patients that was valuable that had a partial response with a minimal residual disease negative condition in the bone marrow OLED. The results are obviously very encouraging. Furthermore, as you can see we have initial good.

Durability in the Follicular patients.

Christian Itin: Summarizing on slide 23, in summary, we have a very favorable starting point that we're now exploring in a larger patient group. We expanded the cohorts for the purpose of having extended follow-up on these patients in order to understand the profile and then to support the decision-making around further clinical development and other indications. We plan to have further data presentations at EHA in June this year. Switching to slide number 25. On the right-hand table, we provide a quick summary of the basic experience that we had to date with OBCell in pediatric patients in the CAR-PAL study.

Summarizing on slide 23 in summary, we have a very favorable starting point that we're now exploring in a larger patient group, we expanded the cohorts for the purpose of having extended follow up on these patients in order to understand the profile and then to support the decision making around further clinical development in those indications we plan to have further data presentations at <unk>.

And this year.

Switching to slide number 25.

On the right hand table, we provide a quick summary of the basic experience that we had to date with <unk> in pediatric patients in the car Pallas study the fundamental finding was that we have excellent activity no cytokine release related.

Christian Itin: The fundamental finding was that we had excellent activity, no cytokine-release-related severe toxicity, but we did see about half of the patients relapse over time, and those relapses were due to loss of the CD19 antigen. That's why we went back and built on this favorable profile of OBCL with its exceptional persistence as well, adding a highly potent CD22 card to create Auto One 22, which is a program that we're obviously moving forward from a lifecycle management perspective.

Severe toxicity, but we did see about half of the patients relapse overtime, and obviously lapses were due to loss of CD 19 antigen.

That's why we went back and built on this favorable profile of L. B cell with its exceptional persistence as well, adding a highly potent CD 22 car to create Ottawa 'twenty two.

Which is a program that we're obviously moving forward from a lifecycle management perspective.

Christian Itin: To date we've been able to show a high degree of activity in preclinical models and did obviously share some of the data at the ASH conference. Obviously the product is highly potent and we believe has the right properties to make a difference in the pediatric patients. This program is now obviously in clinical evaluation in an extension of the CARPAL study and we expect to update you with first actual clinical data at the EHA meeting in the middle of the year. Moving to slide 29.

Moving to slide 26 today to have been able to show a high degree of activity in preclinical models.

Data, obviously share some of that data.

At the Ash conference obviously, the product is highly potent and we believe has the right properties.

To make a difference in the pediatric patients. This program is now obviously in clinical evaluation and an extension of the car powered study and we expect to update you with first actual clinical data at the ehi meeting individually once a year.

Christian Itin: I won't dwell on this slide given it has been presented before, but to remind you, the ALDA IV program is in clinical exploration, and we plan to provide a clinical update, actually the first clinical data from our dose escalation study at EHA this year. Moving to slide 30, when we look at the technology, obviously Autolus has a wide range of technology developed.

Moving to slide 29, we're actively exploring T cell lymphoma, which is an aggressive disease with very poor prognosis for patients I won't dwell on this slide you announced and presented it before but to remind you. The order of four programs in clinical exploration and we plan to provide a clinical update actually first clinical data from our dose.

Escalation study.

This year as well.

Christian Itin: There will last few years with a hundred patent families on the prosecution, which is obviously a very significant technology treasure chest that we're building on and gives us an ability to really create very specific and very detailed properties in our product. [inaudible] In addition to our hematology pipeline, Autolus has also developed, obviously, this building on this modular engineering strategy to solve challenges, particularly not only the hematological malignancies, but also in the solid tumor setting. By engineering T-cells with multiple modules, we can generate complex therapeutics with multiple properties.

Moving to slide 30, when we look at the technology. Obviously, although this has a wide range of technology developed over the last few years with 100 patent families onto prosecution.

Which is obviously a very significant technology treasure chest that we're building on that gives us an ability to really create very specific and very detailed properties in our products in.

In addition to our hematology pipeline Alturas has also developed obviously this building on this module reengineering strategy.

<unk> challenges and particularly not only the hematological malignancies, but also in the solid tumor settings.

T cells with multiple modules that could generate complex therapeutics.

With multiple properties.

Christian Itin: One of the key areas that obviously we've been engaged in is related to the several modules that we have included into the Auto6-NG program. Now, moving to slide 31, this is just a quick look at a new piece of technology that we just published on, which actually allows us to express particular protein modules at very low levels in our CAR T-cells. And this is important, particularly if you look at agents that have very high biological activity, like interleukin-12.

One of the key areas that obviously, we've been engaged in is related to the several modules that we have included into the auto six Mg program.

Now moving to slide 31, it's just a quick look at a new piece of technology that we just published some.

Which actually allows us to express.

Particular protein modules at very low levels.

In our car T cells and this is important particularly if you look at agents that have very high biological activity like interleukin 12 months and what we've been able to show is obviously that we can deliver interleukin 12 get the desired benefit, but we avoid the toxicity that comes along with exposure to systemic I hope.

Christian Itin: And what we've been able to show is obviously that we can deliver interleukin-12, get the desired benefit, but we avoid the toxicity that comes along with exposure to systemic IL-12 secretion. So it highlights in a very nice way, I think, the utility of controlled expression and actually controlling expression of highly potent, potentially toxic gene product. Moving to slide 32, we have a series of next generation programs that use our modular technologies in various forms.

12 situation.

So highlights in a very nice way I think the utility of controlled expression and actually controlling expression of highly potent potentially toxic gene products.

Moving to slide 32, we have a series of next generation programs to use our module with technologies in various forums.

Christian Itin: I just wanted to reiterate our Solid Tumor Program, ALDA6-NG, which is going to be in the clinic middle of the year, which is building on multiple programming modules. And one particular module, obviously, that we are using with that program is the support of long-term persistence in the case of the CCR module that we're including in ALDA6-NG. So with that, we're moving to slide 33, and I will pass over to Andrew for the fourth quarter of 2020 financial update. Andrew.

I wanted to reiterate our solid tumor program.

All of the six Mg, which is going to be integrating middle of the year.

Which is building a multiple programming modules and.

One particular module, obviously that we are.

Using with desk program is the support.

All of long term persistence in the case of the CCR module that.

Including all of the <unk> century.

So with that we're moving through slide 33, and it will pass over to Andrew for the fourth quarter 2020 financial update Andrew.

Andrew Oakley: Thanks, Christian. And good morning or good afternoon to everyone. So we're on slide 34. And it's my pleasure to review our financial results for the fourth quarter to December 31, 2021. So starting with our cash position, cash at December 31, 2021 totaled $310.3 million, as compared to $153.3 million at December 31, 2020. Net total operating expenses for the 12 months ending December 31, 2021 were $165 million.

Thanks, Christian and good morning, or good afternoon children. So if we were on slides 34, and it's my pleasure to review our financial results for the fourth quarter to December 31, 2021, so starting with our cash position cash at December 31, 2021 totaled 302.

$3 million as compared to Q3.

$3 3 million.

At December 31, 2020.

Net total operating expenses for the 12 months ending December 31, 2021 465.

Andrew Oakley: That's net of grant income and license revenue of $2.3 million. And that compares to net operating expenses of $168.1 million, dollars net of grant income and license revenues of 1.7 million dollars for the same period in 2020. Research and Development Expenses remained relatively flat at $134.8 million for the year ending since 31 2021, and it compares to $134.9 million for the comparative period last year. Cash costs, which excluded depreciation and monetization as well as share-based compensation, increased to $121.4 million from $116.9 million.

Dollars.

That's native grant income and license revenue of $2 $3 billion and that compares to net operating expenses of $168 1 million.

Dollars net of grant income and license revenues of one $7 million for the same period in 2020.

Research and development expenses remained relatively flat at $134 $8 million for the year ended December 31 2021.

Compares to $134 9 million for the comparative period.

Last year our cash.

Cash costs, which exclude depreciation and amortization as well as share based compensation increased to 121 4 million from $116 9 million the increase in research and development cash costs of $4 $5 million consisted primarily of an increase in compensation and employment related costs of $3.

Andrew Oakley: The increase in research and development cash costs of $4.5 million consisted primarily of an increase in compensation and employment-related costs of $3.8 million due to a combination of an increase in employee headcount to support the advancement of our product candidates in clinical development and the severance payments related to the reduction in workforce that was initiated during the first quarter of 2021. Secondly, an increase of $2.5 million in facility costs related to continued scaling and manufacturing operations, and thirdly, an increase of $2.4 million, in purchased consumables used in the manufacturing process of Obesol for the FELIX study.

$8 million due to a combination of an increase in employee head count to support the advancement of our product candidates in clinical development and the severance payments related to the reduction in workforce that was initiated during the first quarter 2021, secondly, an increase of $2 $5 million and facility costs related to the continued scaling of meta.

Thanks shrink operations.

And thirdly, an increase of $2 $4 million.

Purchase consumables used in the manufacturing process, if I'd be so Felix study.

Andrew Oakley: Fourth, an increase of $0.9 million in IT infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations. And lastly, an increase of $100,000 for cell logistics, which is offset by a reduction in clinical trial costs of $5.2 million overall. Non-cash costs decreased to $13.4 million for the year ended December 31, 2021 from $18.1 million for the previous period last year. The $4.7 million decrease of non-cash costs is related to a decrease of $7.7 million of share-based compensation expense as a result of the lower fair value of auctions recognized during the period and due to the reduction in workforce that was initiated in the first quarter last year.

And fourth an increase of zero point $9 million in it infrastructure and support from <unk> systems led to the conduct of clinical trials and manufacturing operations and lastly, an increase of $100000 right to sell logistics, which is offset by a reduction in clinical trial costs of $5 2 million carloads overall.

Noncash costs decreased to $13 $4 million for the year ended December 31, 2021 from $18.1 billion for the previous period last year, the $4 7 million a decrease of noncash constitutes related to a decrease of $7.7 million of share based compensation expense as a result of a lower fare.

Value of options recognized during the period and due to the reduction in workforce that was initiated in the first quarter of last year and that was offset by a $3 million increase in depreciation expenses.

Yes.

Andrew Oakley: That was offset by a $3 million increase in depreciation expense. General and administrative expenses decreased to $31.9 million for the year ending December 31, 2021 from $35 million for the year ending December 31, 2020. Cash costs, which, as I've explained, exclude depreciation as well as share-based comp, decreased to $26.7 million from $27.4 million.

General and admin expenses decreased to $31 $9 million for the year ending December 31, 2021 from <unk> $5 million for the year ending December 31, 2020 cash costs, which as I've explained exclude depreciation as well as share based comp decreased to $26 7 million.

Others from $27.4 million, there were decreases of zero point $7 million related.

Andrew Oakley: There were decreases of $0.7 million of costs, and that relates to, firstly, $0.8 million of expenses related to the company's commercial preparation activities, $0.6 million of employee compensation due to the reduction of workforce in the first quarter of 2021, and lower retention costs. Thirdly, $0.5 million of facilities costs. And fourthly, $100,000 in general admin expenses, which all of that was offset by increases in directors and offices insurance and IT infrastructure and support for information systems of $1 million and $0.3 million respectively.

Costs and that relates to firstly 0.8 million.

Expenses related to the company's commercial preparation.

Activities.

$6 million of employee compensation June due.

Due to the reduction of workforce in the first quarter of 2021 and lower retention costs.

Thirdly, 0.5 million in facilities costs and fourthly.

$100000 in general and admin expenses, which all of that was offset by increases in directors and officers insurance and it infrastructure and support for information systems, and $1 million and zero point $3 million respectively.

Andrew Oakley: Non-cash costs decreased to $5.2 million for the year ending December 31, 2021 from $7.6 million for the corresponding period last year. The $2.4 million decrease in non-cash costs is mainly attributed again to lower share-based compensation expenses recognized during the period and due to the reduction in the workforce that was initiated during the first quarter of 2021. Interesting income decreased to $0.3 million for the year, which compares to $0.5 million for the year ending at $3,131.20.

Noncash costs decreased to $5 $2 million for the year ended December 31, 2021 from $7 $6 million for the corresponding period last year.

$2 $4 million a decrease of noncash cost is mainly attributable attributed again to lower share based compensation expenses recognized during the period and due to the reduction in workforce that was initiated during the first quarter of 2021.

Interesting income decreased to $7 $3 million for the year.

That compares to zero point $5 million.

Year, ending December 31, 2020.

Andrew Oakley: Decrease is due to lower cash balances held combined with lower interest rates for cash that's on deposit. Interest expense increased to 1.1 million dollars for the year ending December 31 2021 and that relates to the liability relating to the sale of future revenue which arose upon entering into the collaboration and financing agreement with Blackstone. Income tax benefit decreased to $23.9 million for the year ending December 31-21 from $24.2 million for the corresponding period last year.

Decrease was due to lower cash balances held combined with lower interest rates for cash thats.

Does it.

Interest expense increased to $1 $1 million for the year ending December 31, 2021, and that relates to the liability relating to the sale of future revenue.

Which arose upon entering into the collaboration and financing agreement with Blackstone.

Income tax benefit decreased to $23 9 million for the year ended December 31 21.

From 24.2 million for the corresponding period last year.

Andrew Oakley: This is due to a small decrease in research and development expenditures which were qualifying for the tax credits for the year. And as R&D credits fell at a faster rate than the company's net loss before income tax, this led to a lower effective tax rate. Research and development credits are obtained at a maximum rate of 33.35% of the company's qualifying research and development expenses, and the decrease in the net credit is primarily attributable to a decrease in eligible expenditure.

This is due to a small decrease in research and development expenditures, which qualify for tax credits for the year.

And as R&D credits fell at a faster rate than the company's net loss before income tax this led to a lower effective tax rate.

Research and development credits are obtained at a maximum rate of 33.35% of the Companys qualifying research and development expenses and the decrease in the net credits primarily attributable to a decrease in eligible expenditure.

Andrew Oakley: The net loss attributable to ordinary shareholders was $142.1 million for the 12 months ending December 31, 2021, and that compared to $142.1 million. $1 million for the same period in 2020. The basic and diluted net loss per ordinary share for the 12 months ending December 31, 2021 totaled a loss of $1.97 compared to the basic and diluted net loss per ordinary share of $2.76 to the corresponding period last year.

The net loss attributable to ordinary shareholders was $142 1 million for the 12 months ending December 31, 2021, and that compared to 142 point.

$1 million for the same period in 2020.

The basic and diluted net loss per ordinary share for the 12 months ending December 31, 2021 totaled a loss of $1.97 compared to basic and diluted net.

Loss per ordinary share of $2.76 for the corresponding period last year.

Andrew Oakley: Autolus, estimates that it's current cash on hand and anticipated milestone payments from Blackstone will extend the company's run cash runway into 2024. And with that, it would be remiss of me before I hand the call back to Christian to not thank Christian for his kind words. I've enjoyed my time working with Christian and the management team and I certainly wish Lucy all the best. Lucy's promotion is very well deserved and I have the utmost confidence that she will excel.

Ultras.

<unk> estimates that its current cash on hand, and anticipated milestone payments from blacks Blackstone will extend the company's run cash runway into 2024.

And with that it would be remiss of me before I hand, the call back to Christian to not think Christian <unk>, calling woods.

I've enjoyed my time, working with Christian and the management team and I certainly wish Lucie all the best Lucia promotion is very well deserved and I have the utmost confidence that she will excel and on leaving the finance function at all and very capable hands.

Christian Itin: And I'm leaving the finance function at Autolus in very capable hands. And with that, I'll hand back to Christian to give you the part line of brief outlook on expected milestones Christian. Thanks a lot, Andrew. I'm moving to slide 36.

And with that I will hand back to Christian to give you an overview of the pipeline in brief that book unexpected milestones Christian.

Christian Itin: Five of the next steps we believe we have exciting months ahead of us with OVCEL running through the Felix study in adult LL, delivering initial clinical data from this pivotal study later this year and with full data expected in the first half of 2020. We've also guided that we plan to provide clinical updates from a number of our other programs at EHA in June of this year, namely OVCEL in BNHL and CLL patients from the old COVID Extension study. OVCEL data in primary CNS lymphoma from the carousel study.

Thanks, a lot Andrew.

Moving to slide 36, 500 next steps. We believe we have exciting months ahead of us with Ob sell running through the Felix study in adult day L. L. Delivering initial clinical data from this pivotal study later this year and with full data expected in the first half of 2023. We've also guided that we plan to provide clinical labs.

Data from a number of our other programs at <unk> in June of this year, namely Ob sell in NHL in CML patients from the old car extension study Ob sell data and primary CNS lymphoma from the Carousel study.

Operator: OTA-122 clinical data in the extension of the CAR-PAL study and clinical data from the dose escalation work we've done with OTA-4 in primary T-cell lymphoma also at EHA. This is in addition to progress across the pipeline with Auto 6 and GEQ changing to the clinic in mid-2022 and actually Auto 8 being rather imminent in terms of the start of phase one. Finally, as a result of our collaboration with Blackstone, we're in a strong position with a cash runway, as you heard from Andrew, including project financing payments from Blackstone, which gets us into 2024. We're now happy to take questions. And thank you. As a reminder, to ask a question, you'll need to press star one on your telephone.

<unk> 22 clinical data in the extension of the car Pallas study.

And clinics.

Clinical data from the dose escalation work, we've done with all four in prime the T cell lymphoma also.

Yeah.

This is in addition to progress across the pipeline with all the <unk> to enter the clinic in mid 2022 and actually auto eight.

Yes.

Rather imminent in terms of the start of the phase one study.

Finally, as a result of our collaboration with Blackstone, we're in a strong position with a cash runway as you heard from Andrew including project financing payments from Blackstone, which gets us into 2024, we're now happy to take questions.

And thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby we compile the Q&A roster.

Operator: Please stand by as we compile the Q&A rosters. And our first question comes from Gil Blum, from Needham & Company. Your line is now open.

And our first question comes from Gill from Needham <unk> Company.

Your line is now open.

Yes.

Gil Blum: Good morning and good afternoon, guys. Thanks for taking our questions. Just a few from us.

Good morning, and good afternoon.

Hi, Thanks for taking our questions.

Just a few from us so.

Christian Itin: So, first of all, there were some delays in the FELIX study due to COVID. Are you guys taking any strategic moves to quote-unquote COVID-proof the FELIX study? All right, Gil.

First of all.

There were some delays on the Felix studies due to Covid are you guys thinking any street.

<unk> moved to <unk>.

Quote unquote Covid proof the Felix study.

Yes.

Christian Itin: First of all, thanks a lot for joining. I was thinking you have more than one question, so I was waiting for the next question to come. I'm happy to answer the Felix question.

Alright ill first of all thanks, a lot for joining us.

He was thinking you have more than one question. So that was waiting for the next question to come.

Happy to answer that.

Felix question, So I wanted to correct.

Which I do appreciate it.

Christian Itin: Which I do appreciate. So with regards to the Felix study, obviously as we're getting into the fourth quarter, obviously we have very significant impact on many centers, not only the UK but also across the U.S., first on the tail of the Delta surge and then basically moving straight into the Omicron surge. What we're seeing across the centers is that there is a very significant reduction of and frankly loss of nursing staff that we've seen, actually this is across Europe as well as across the U.S., with many centers actually struggling to keep clinical trial operations going irrespective of the nature of the clinical trial. Most centers are back online at this point, but there's still a few centers in the U.S. that are not in a position where they can actually operate clinical trials.

So with regards to the Felix study, obviously as we're getting into the fourth quarter.

Obviously, we have very significant impact on many centers not only the UK, but also across the U S. First on the tail of the Delta search and then basically moving straight into the army Chrome search.

What we're seeing across.

The centers is that there is a very significant.

The reduction of.

And frankly loss of nursing staff.

That we see.

Actually this is across Europe , as well as across the U S.

With many centers actually struggling to keep our clinical trial operations going irrespective of the nature of the clinical trial.

Most centers are back online at this point, but theres still a few centers in the U S that are not in a position where they can actually operate clinical trials, we expect that to actually now to lessen as we get.

Christian Itin: We expect that to actually now to lessen as we get further into the year. And we certainly see an upswing kind of starting in January and then gradually moving up. I think we've done everything that is possible to quote-unquote COVID-proof the trial, but we need to remember, you know, these patients do require significant access and support at the respective centers and, you know, there is, it requires obviously significant operating, properly operating infrastructure at the center and unfortunately that is because it's linked to staffing.

Further.

The year and we certainly see an upswing kind of starting in January and then gradually moving up.

I think we stopped everything that is possible to quote unquote.

Colby proof the trial.

But we need to remember these patients do require significant access and support at the respective centers.

There is a requires obviously significant operating properly operating infrastructure at the center.

Unfortunately that is because it's linked to staffing.

Christian Itin: Those issues are not fast in sort of terms of the time it takes to fix them and frankly are a longer-term challenge, I think, for many of the hospitals to sort of actually get back their staffing levels and training levels.

Those issues are not fast.

In terms of the at the time it takes to fix them.

Frankly are a longer term challenge I think for many of the hospitals to sort of actually get back their staffing levels and training levels.

Christian Itin: But I think within the study, I think we've done what is possible and I think we now have, you know, very steady flow of patients as we're progressing the study, and maybe moving to the pretty data rich he had of you. Specifically for the DLCCL cohort, are we going to see additional patients in addition to those that you've already discussed? Yes, we keep enrolling in those cohorts. You know, each cohort is designed for about 10 patients each.

But I think within the study is simply stand what is possible and I think we're now has a very steady flow of patients as we're progressing the study.

Okay.

Maybe moving to the a pretty data rich <unk> ahead of you.

Specifically for the deal PCL cohort or are we going to see additional patients.

In addition to those that you've already discussed.

Yes, we can.

Keep enrolling in.

In dose cohorts.

Each cohort is designed for about 10 patients. Each so we've continued to enroll patients into the L. T cell cohort as well as the other cohorts as well.

Christian Itin: So we continue to enroll patients in the DLDCL cohort, as well as in the other cohorts as well. Okay, and maybe a quick competitive question on AUTO-122. So again, from a competitive standpoint, how common is a CD19 negative relapse in patients that are currently being treated with commercial CAR-T? And is the rate similar to the one that you guys observed with your own study? It's a very good question.

Okay.

And maybe a quick competitive question on auto 122.

Again from a competitive standpoint, I'll comment as a CD 19 negative relapse in patients that are currently being treated with commercial card fees.

As the rate similar to the one that you guys observed with your own clinic.

Christian Itin: And I think we're still in the process of collecting data, I think, across the field. And what we're seeing, I think, is clearly that, particularly for the pediatric ALL patients, this is the predominant cause of relapse that we're seeing. Remember, however, looking into other indications, be it DLDCL or some of the other non-Hodgkin's indications, it is clearly a contributor to relapse, but it certainly doesn't seem to be as prominent a driver for relapse.

This is a very good question and I think we're still in the process of collecting data I think across the field.

But we're seeing I think is clearly that.

Particularly for the pediatric.

AML patients. This is the predominant cause of relapse that we're seeing.

Weber have ever looking into.

Other indications <unk> bcl or some of the other non Hodgkin's indications it is clearly a contributor.

To relapse, but it certainly doesn't seem to be as prominent a driver for relapse, but clearly within pediatric allo Leds. It's the predominant driver one of the key things we're looking forward.

Christian Itin: But clearly, within pediatric ALL, it's the predominant driver. One of the key things we're looking forward, in terms of the data from the FELIX study, is actually to see to what extent antigen loss is driving relapses in adult patients. And I think there, we still don't have enough data. And one of the key, I think, factors there is, in order to be able to see the impact of target negative or CD19 loss as a driver for relapse, is that, obviously, you have to have products that are very long-persisting, so you can exclude, actually, a potential contribution of the relapse due to, potentially, just loss of the CAR T cells, which obviously is one of the drivers that can actually lead to relapse itself.

In terms of the data from the Felix studies actually to see to what extent antigen loss is driving relapses in adult patients and I think there we still don't have enough data and one of the key I think factor series in order to be able to see the.

The impact of target negative for CD 19 loss as a driver for relapses that all of them.

You have to have products that are very long persisting. So he can exclude.

Actually a potential contribution.

After relapse due to potentially just loss of the car T cells, which obviously is one of the drivers that could actually lead to relapse itself. So I think with Ob Silva as a real opportunity to evaluate that in a very stringent way given that we have very long persistence with the product.

Christian Itin: So I think with ob-cell, we have a real opportunity to evaluate that in a very stringent way, given that we have very long persistence with the product. And with that, that contribution, a potential contribution of CD19 loss, I think will become very visible. Obviously, the initial experience that we have in our first experience in the old CAR study and the 1B portion of the FELIX study, obviously, we've seen some CD19 negative relapses. But obviously, those were limited, and certainly not in the magnitude that we have seen prior in the pediatric.

With that that contribution or potential contribution of CD 19 loss I think will become very visible obviously the initial experience that we have in our <unk>.

First.

The experience of the old car study and the <unk> portion of the Felix study, obviously, we've seen some CD 19 negative relapses.

Obviously, there is more limited and certainly not in the magnitude that we have seen prior in the pediatric patients.

Okay.

That's a great summary.

And.

Christian Itin: Okay, that's a great summary. On AUTO VIII, it looks like there's a start of a Phase I in the first half. Have we received any additional details on this program? you know, the nitty gritty of what the targets are or did I miss this?

On auto as well.

Looks like there's a startup of phase one in the first half, but we've received any additional details on this program.

Good.

The nitty gritty of what the targets are or did I Miss this.

Christian Itin: We haven't updated on that. I think we're going to be, we'll be talking about that when the study is up and running. And obviously, we'll, we'll spend some time on that program. But obviously, it is at this point still early and want to make sure the program is running properly in the clinical, in the clinical study, and then we'll start to talk about it more. All right, and one last one for Andrew because he's gonna be leaving us. Um, are the BlackRock Milestones front or back?

We have an updated on that I think we're going to be we'll be talking about that when the study is up and running.

<unk> will spend some time on that program, but obviously it is at this point, it's still early and we want to make sure of the program is running properly and the clinical in the clinical study and then we'll start to talk about it more.

Alright, and one last one for Andrew because he is gonna be leaving us.

Are the <unk>.

Barack milestone front or back ended.

Andrew Oakley: Gil, thanks for the question. I mean, I think what we've said is that the milestones are related to development and regulatory milestones, so that probably just gives you an idea in terms of when we would expect to proceed. Okay, Andrew, you will be missed and thank you guys for taking our questions. Thanks Gil.

Thanks for the question I mean.

I think what we've said is that the milestones related to development regulatory milestones. So that probably gives you an idea in terms of when we would expect to see.

For CECO.

Okay. Okay.

Andrew you will be missed.

You guys for taking our questions.

Thanks, Gil Thanks, a lot bill.

Thank you.

Gil Blum: Thanks a lot Gil. Thank you. And our next question comes from Mara Goldstein from Mizzou. Do you mind if I open?

And our next question comes from Mara Goldstein from Mizuho.

Your line is now open.

Mara Goldstein: Great, thanks so much for taking the questions. I just wanted to ask, you know, you'll obviously have a big EHA update this year, and so when do you think you'll be in a position to talk about potential next steps for, you know, the All-CAR-19 extension, cohorts, and Auto-122 as well, or rather, excuse me, not Auto-122, but also carousel in the CMS lymphoma? Thanks for joining, Mara, and thanks for the question.

Great. Thanks, so much for taking the question.

To ask you obviously have a big <unk> update this year and so when do you think you'll be in a position to talk about potential next steps for.

The all cart 19 extension cohort and Ottawa in 'twenty two.

That's why I don't I'd, rather excuse me not on a 122, but also have carousel in that in that CNS.

Lymphoma.

Thanks, and thanks for joining marathon and then thanks for the question.

Christian Itin: Obviously, what we're doing in the all-car study is evaluating the profile of ob-cell in those indications, and when we look at the respective indications, there are several, I think, aspects that matter in terms of assessing the potential of the product. One is, I think for all of those indications, you want to see a good and very well-manageable safety profile, and I think we start to get a pretty good view on that, and the consistency of the data, I think, is very encouraging.

Obviously, what we're doing in the old car study is evaluating the profile of Ob selling those indications and when we look at their respective indications.

That's a good segue.

I think aspects that matter in terms of assessing the potential of the product. One is I think for all of those indications you want to see a good and very well manageable safety profile and I think we start to get a pretty good view on that and the consistency of the data I think is very encouraging.

Christian Itin: The second aspect is that you want to see a high degree of clinical activity that is sustained over time, and clearly, as we're looking at the various indications, we do need, obviously, a certain amount of follow-up, and I think we'll start, as we get through the middle of the year and into the second half of the year, actually to have, I think, a good level of follow-up, particularly on the follicular lymphoma patients, and we're starting to build, obviously, also on the DL-BCL patients as well, and are adding on CLL and some more mantle cell experience. So I think as we're going to the course of the second half of the year and get to the end of the year, I think we start to get a pretty good view on the respective relative profile that we have also for the program in the respective sub-indications. For primary CNS lymphoma, obviously, this is a smaller study that we do on the academic side together with our collaborators at UCL.

The second aspect is that you want to see a high degree of clinical activity that is sustained over time.

And clearly as we're looking at the various indications we.

We do need obviously, a certain amount of follow up and I think we'll start as we get through the middle of the year and into the second half of the year.

Actually do you have I think a good level of follow up particularly on the Follicular lymphoma patients.

And we're starting to build obviously wholesale bcl patients as well and are adding on C. L. L.

Some more mantle cell experience.

Think we're as we're going through the course of the second half of the year and get to the end of the year I think we start to get a pretty good view on the respective relative profile that we have also for the program in the respective sub indications for primary CNS lymphoma. Obviously this is a smaller study that we do on the academic side together with our collaborators.

UCL.

Mara Goldstein: And this particular program is exploring, obviously, the utility of CAR-T in that very challenging patient population. What we'll have at EHA is initial data from the initial patients that we have that were treated. And I think we're going to gain more experience as we treat more patients, particularly second half of the year as well. But I think overall, we start to get a pretty good view on the range of profile that we have in those indications middle of the year.

This particular program is exploring obviously the utility of the car T.

All the sell in that.

Challenging patient population, what will have an EHR as initial data from the initial patients that we have that were treated.

And I think we're going to gain more experience expert treat more patients, particularly second half of the year as well, but I think overall, we start to get a pretty good view on the the range of profile that we have in those indications middle of the year and I think when it comes to durability, I think a pretty a pretty clear picture.

Mara Goldstein: And I think when it comes to durability, I think a pretty clear picture by the end of this year with the extended follow-up. All right. Thank you so much. And Andrew, good luck and enjoy retirement. Thanks, Mara.

By the end of this year with the extended follow up.

Alright. Thank you so much Ana Andrew good luck and enjoy rich.

Hi, Amit.

Thanks, Laura.

Nick Adit: Thank you. And our next question comes from Nick Adit from Wells Fargo. Your line is now open.

Thank you and our next question comes from Nick Abbott from Wells Fargo.

Your line is now open.

Christian Itin: Terrific, thanks for taking our questions, and my congratulations to Andrew, too. Just go back to the theme that's still, it's obviously a gigantic hole in the ground at the moment, but so when do you expect to be able to start sort of PPQ activities, and then, you know, you said it'll support around about 2,000 doses per year. You know, to increase that, do you excel, to just build out, you know, the existing shell? And I have a follow-up. Yeah, very good.

Terrific, Thanks for taking our questions.

And Mike Congratulations to Andrew too.

Just go back to the steepness.

It's a gigantic hole in the ground at the moment.

But so when do you expect to be able to start so the P. P Q activities and then.

You said it'll split around about 2000 doses per year.

Yeah.

To increase that Gallo to just build out the.

The existing shale and I have a follow up thanks.

Christian Itin: Well, thanks for joining us, Nick. I really appreciate it. Another early day on your side.

Very good well thanks for joining Nick really appreciate it another early day on your side.

Christian Itin: So the Stephen H. Facility, obviously, you see this in the February picture, obviously a lot of the groundwork that has been done. The actual facility is actually built, most of it is built actually in a factory, and so they're all prefabricated modules. So as soon as the ground actually has been ready, obviously, the actual time to wreck the building is very quick, and we're starting to see now the building get off the ground in a very nice pace and smack on time.

So Stephen H facility, obviously, you see this as of February picture, obviously, a lot of the ground work that's been done the actual facility is.

Actually built most of it is built actually in the factory.

And so that all prefabricated modules so as soon as they hit the ground actually it's been ready all the savings that the actual time to Rex to building is very quick and we're starting to see now the building get off the ground.

A very nice pace and smack on time.

Christian Itin: So what we're planning to do is actually be able to take on the building towards the end of the year and then run the PPQ activities in the first part of 2023. So it gives us kind of the right timeframe and sequence for the VLA file, and we'll be in time to support it. In terms of increasing capacity, the current facility, as indicated, supports about 2,000 batches a year.

So what we're planning to do is actually be able to actually.

Take take all the building towards the end of the year and then won the PDQ activities in the first part of 2023.

So it gives us.

Kind of the right timeframe it sequence into into the BLA file and will be in time to support it in terms of increase in capacity. The current facility as indicated supports about 2000 batches a year.

There's probably a bit more room to expand.

Upwards on that by operating at a slightly higher density. However, there is a literally.

Christian Itin: There's probably a bit more room to expand upwards on that by operating at a slightly higher density. However, there is literally the site next to where we're currently building that is actually available and could be used for an extension of the building, which will actually give just an extended overall operating environment that we can use in Stevenage. Now what we will do is we'll balance, if you look longer term, the manufacturing capacity in the UK with, you know, at some point, a second site, and that's obviously one of the things that we're looking at. Very likely, it will take time to sort of consider a second site in the US.

Site next to where we currently building.

It is actually available and could be used for an extension of the building, which actual case.

It's just an extended overall operating environment that we can use in Stevenage.

Now what we'll do is we'll balance if at all.

Look longer term.

Manufacturing capacity in the U K with.

At some point the second site and that's obviously one of the things that we're looking at.

Likely it would make over time to sort of consider a second site in the U S.

But that obviously is downstream and post launch of the product.

Christian Itin: But that obviously is downstream and post-launch of the product. So for now, the facility actually is exactly what we need. It allows us to cover, actually, we believe, the full opportunity in the adult data. Thank you. So, you know, I think you've said that. Felix PLA target is 2H23. Can you talk about timing for European submission? And then how do you think about partnering options for Japan or greater China? Yeah, very good question.

So for now that the facility actually is exactly what we need and it allows us to cover actually we believe the full opportunity in the adult setting.

Alright, thank you.

So I think you said the Felix.

Helix BLA target is to reach 23 can you talk about timing for European submission and then how do you think about partnering options, but Japan greater China for example.

Christian Itin: So as we had indicated, obviously, we expect full data first half of 23, which gives us an ability to drive to a BLA filing second half of 23. Now, as we're thinking through the sequencing of an opportunity of sequencing in terms of different regulatory jurisdictions, obviously, the primary focus is on the BLA and the US market for very obvious reasons. But there is also opportunity to potentially also take a faster path in the UK, which is currently under exploration under the so called ILAP process, which is a designation we've received and gives us an opportunity to have conversations around that.

Yes, very good question so.

As we had indicated all this we expect full data.

First half of 'twenty, three which gives us an ability to drive to a BLA filing second half of 'twenty three.

As were thinking through the sequencing off.

The opportunity of sequencing in terms of difference.

Regulatory jurisdictions.

I would say the primary focus is on the BLA.

The U S market for very obvious reasons, but there is also opportunity to potentially also take a.

A faster path in the U K, which is currently under under exploration.

Under the so called <unk> process, which is a designation we've received it gives us an opportunity to have conversations around that we'll see kind of what the timing looks like around that but there may be an opportunity for an accelerated path in the U K as well not too dissimilar from what you typically would see in the U S.

Christian Itin: We'll see kind of what the timing looks like around that. But there may be an opportunity for an accelerated path in the UK as well, not too dissimilar from what you typically would see in the US. We would think about the European approach in a staggered way to the US activities and would sort of in sequence after the BLA filing, consider filing in the EU as well.

Think about the European approach in a staggered way to the.

The U S activities.

And what sort of in sequence.

After the BLA filing considered filing in the EU as well.

Typically as you.

I'm sure are well aware.

Christian Itin: Typically, as you I'm sure are well aware, the review timelines tend to be longer in the EU. So there will be sort of a staggered build in terms of approvals over time just based on the regulatory review timelines that we've seen in the, So that's sort of the role that we're currently looking at, and then you're pointing to the fact that the globe doesn't end beyond, you know, with the U.S. and Europe, it goes quite a bit beyond that, and so we're clearly looking at opportunities in kind of Asia-Pacific area as well, and that is sort of under investigation, but there is not enough guidance at this point in time of when we're planning to sort of get into those areas and start to be active, from a development or or. Terrific. Thanks a lot, Christian. Alright, that's a lot, Nick.

The radio timelines tend to be longer in the EU, so that would be sort of a staggered beyond in terms of approvals that over time, just based on the regulatory review timelines that we've seen in the space.

So that's sort of the role that we're currently looking at and then you pointed to the fact that the can.

I hope this has been the armed.

With the U S and Europe that grows quite a bit beyond that and so we're clearly looking at opportunities.

Asia Pacific area as well.

They set a voluntary investigation.

No not at all that the guidance at this point in time of labor planning to sort of get into those areas and start to be access.

From a development or or a commercial perspective.

Terrific. Thanks, a lot Christian.

Alright, Thanks, a lot Nick.

Nick Adit: [inaudible] And thank you. And our next question comes from Asthika Goonewardene from Truist. Your line is now open.

And thank you and our next question comes from Al <unk>.

Luca.

Darby truest.

Your line is now open.

Asthika Goonewardene: Hi, this is Bill on for Asthika. We were wondering about any potential updates or clinical initiations for AUTO7 or the ALO program or any sort of color regarding those. Thanks. Right, so the Auto-7 is certainly a program that we've pushed, we did push back from a priority perspective. The focus is on Auto-6 NG on the solid tumor side, and also actually obviously collecting and reviewing some of the data that we've seen in the space of PSMA targeting, which is obviously a mixed picture and is an area we're looking at very carefully.

Hi, This is bill on for Africa.

We were wondering about any potential updates or clinical initiations for auto seven or the allo program or any sort of color regarding those things.

Right. So the auto seven is certainly a program that we've pushed.

They've pushed back from a priority perspective, our focus is on all of the six N G on the solid tumor side.

And also actually obviously collecting and reviewing some of the data we've seen in the space of the SMA targeting which is obviously, it's a mixed picture and it's an area. We're looking at very carefully.

Asthika Goonewardene: With regards to the ALO program that is actually moving forward at UCL and we expect that study to start in the upcoming months and it's actually all ready to go at this point in time. But auto 7 were pushed back behind auto 6 and G and auto 6 and G as we indicated we will get the clinical study up and running middle of the year. Thank you, appreciate it.

With regards to the Allo program that is actually moving forward.

At UCL.

And we expect that study to start in the upcoming months.

It's actually all ready to go at this point in time.

But all of the seven were pushed back behind Autosave and G. In both <unk> and G. As we indicated.

We will get a get the clinical study up and running middle of the year.

Thank you appreciate it.

Thank you.

Christian Itin: Thank you. Thank you. And thank you. And our next question comes from Matt Pipps from William and Blair. Your line is not open.

And thank you.

Our next question comes from Matt Pips from William and Blair.

Your line is now open.

Matt Pipps: Hi, thanks for taking my questions. Christian, first, do you think the recent label update for Ticardis and ALL based on the cohort 6 data with kind of the steroid prophylactic use, you know, makes any kind of difference as far as physician perception of that product versus a potential Oberstell, Well, first of all, first, thanks for joining that. You know, the use of steroids with CAR T's obviously has been, you know, certainly been quite wide.

Hi, Thanks for taking my questions. Christian first do you think the recent label update for <unk> and a O L. Based on the cohort six data with kind of a steroid prophylactic use.

It makes any kind of difference as far as physician perception of that product versus a potential.

Oh God.

Correct.

Well first off.

Thanks for joining that.

Use of steroids with car Ts, obviously has been.

Christian Itin: And when you look at the data presentations that we've seen from TICARDIS around steroid use, obviously that's been, you know, quite consistently sort of being evaluated and looked at. And in fact, the data we've seen on safety, including the primary label, obviously has already had, you know, quite extensive use of steroids included. So that's actually the first thing. The second is that one of the things that I think has become clear, there is a number of presentations that are out there looking particularly at the steroid use in the context of Giscarda in the OBCL did show an impact on outcome of the patients and particularly challenges to sustain persistence. And certainly that is one of the key challenges we see in ALL is that persistence actually does matter.

Flipping quite wide and when you look at the data presentations that we've seen from to Carter's around steroid use obviously that's been.

Quite consistently sort of being evaluated and looked at that in fact, the data we've seen on safety, including.

The primary label, obviously has already had a quite.

Quite extensive use of steroids included.

So that's actually is the first thing the second is that one of the things that I think because become clear there was a number of presentations that were out there looking particularly at the at the steroid use in the context of just start out in the obese Yale did show an impact on the outcome of the patients in particular challenges to sustain.

<unk>.

And certainly that is one of the key challenges that we see at least a persistence actually thousand matter.

Christian Itin: And also one of the key things that we have been observing with our product is persistence that goes out for two or three years. And certainly that's an area that's been more challenging for the initial product in the space and certainly also the TICARDIS to get actually reasonable level of persistence in ALL. The more aggressive you use steroids, the more that becomes challenging.

Obviously wanted to key things that we have been observing with our properties.

Since that goes out for two or three years and certainly that's an area that's been more challenging for the.

The initial product in the space and certainly also the Carter's to get actually reasonable level of persistence in a L. L.

More aggressive you use steroids to more of that becomes challenging. So I think it's a difficult trade off in terms of the safety signal.

Christian Itin: So I think it's a difficult trade-off in terms of the safety signal, you know, high or intense steroid use has already been part of the, frankly, the treatment before. And we don't think there's going to be any significant change there. It's been pretty much what the centers had to do to sort of actually find a way to manage.

No.

Our intent to steroid use is already a big part of it frankly the treatment before we don't think there's going to be any significant change there that's been pretty much what the centers have to do to sort of actually finalized managed to pull up.

Christian Itin: Thank you. Thanks. I'd ask you guys in the initial kind of Felix data, you highlight it's in difficult or maybe differences in the quality of Luca Faresis, from the safety run in, you know, higher blast counts and things.

Okay.

And I asked you guys in the initial kind of Felix data you highlighted some difficulties or maybe differences in the quality of Leukapheresis from the safety run in you know higher blast counts and things.

Christian Itin: And I don't know if you can think too much on this at this point, but do you feel like the move to the industrialized process is handled appropriately in the part two of Felix? Absolutely. I mean, one of the key things that we have in acute leukemia, one of the challenges is that the patients can have basically an effusion of leukemic cells from the marrow into the blood stream. And you can actually get situations where the patients, when you look at the circulating lymphocytes in the blood, you know, you have 90 or even more percent, above 90% of the cells being leukemic cells.

I don't know if you can say too much on this at this point, but do you feel like the move to the industrialized processes San Luis appropriately in the port to Felix.

Absolutely I mean, one of the key things that we have in acute leukemia and one of the challenges is that.

Patients can have.

Basically.

A an infusion of leukemic cells from the barrel into the bloodstream and you can actually get.

<unk>, where patients when you look at the circulating lymphocytes in the blood you have 90 or even more percent about 90% of the sales being leukemic cells and as you can imagine if that's where you sort of then start Jackson collecting lymphocytes from it means that you. Lucas recently is predominantly consists of leukemic cells with obviously.

Christian Itin: And as you can imagine, if that's where you sort of then start to actually collecting lymphocytes from, it means that your leukophoresis predominantly consists of leukemic cells, with obviously, you know, a low percentage of T cells that you collect, and ultimately, those are the cells we're interested in from a manufacturing perspective.

A low percentage of T cells to be collected ultimate sales were interested in from a manufacturing perspective.

Christian Itin: So what we did, and we spent time on early on as we transitioned the program onto the commercial side, is to make sure that we can actually deal with a wide range of patient conditions so that we're actually in a position to manufacture for almost all patients. That's certainly what we've been able to do, that we're actually gonna include in therapy. And that's been one of the key elements, really, to make sure that we have the ability to treat this wide range of patients and conditions.

So what we what we did and we spent time on early on and as the transition of the program up to the commercial side is to make sure that we can actually deal with a wide range of patient conditions. So that we're actually in a position to manufacture for as.

Almost all patients.

Certainly what we've been able to.

That we're actually going to include.

And two in two therapy.

And that's been one of the key the key elements needed to make sure that we have an ability to include this wide range of patients and conditions.

Christian Itin: And those changes actually did, through the manufacturing process, turned out to actually make sure that we can manufacture for all the patients that we have been able to actually enroll in leukophores. And it gives us an ability to really be able to manufacture, even if the patients tend to be very advanced and in poor condition. So in that sense, it was to make sure that the bandwidth of patients we can actually, frankly, successfully manage is expanded to the maximum extent. And that was a very successful endeavor.

And those changes actually dipped.

To the manufacturing process.

Dio to actually make sure that we can manufacture for all the patients that we have been able to actually enroll and Luc freeze and it gives us an ability to.

To really be able to manufacture even if the patients tend to be.

Very fast and in poor condition.

So in that sense. It is to make sure that the bandwidth of patients. We can actually frankly successfully manage is expanded to the maximum extent.

And that was a very successful endeavor.

Christian Itin: And one last quick one, just to make sure, clarify here, so Topline did Felix in the second half, is that just coming in a press release with maybe something like a response rate, and then we'll get a medical conference presentation in the first half of 2023? I think that is a fair way of looking at it. You don't want to piecemeal the data too much in terms of individual bits and pieces, so it has to be sort of high-level update early on and give an update and be clear kind of what the trial looks like in terms of outcome.

Okay and one last quick one just to make sure clarify here so topline data Felix in second half is that just coming in a press release with maybe some response rate and then we'll get a.

Medical conference presentation in the first half of 'twenty three.

I think that is a fair that's a fair way of looking at it.

You don't want to pay.

Piecemeal the data too much in terms of individual bits and pieces. So it has to be used at a high level update early on.

In.

To give an update and be clear kind of what the trial looks like in terms of outcome, but then obviously a full presentations at medical conferences, obviously they have a key.

Christian Itin: But then obviously a full presentation at the medical conference is obviously the key data release also with a lot of deep dive, which will be done at that point in time. We expect that to be in the first half of 2023.

Data.

Our release also with a lot of deep dive, which will be done at that point in time, we expect that to be.

Yeah first half of 'twenty 'twenty three.

Yep. Thanks Christian.

Matt Pipps: Okay, thanks Matt. Thank you. And our next question comes from A.R. Joseph from J.P. Morgan.

Okay. Thanks, Matt.

Thank you.

And our next question comes from Eric Joseph from JP Morgan. Your line is now open.

A.R. Joseph: Your line is now open. Good morning, good afternoon, thanks for taking the questions. On Felix, or part two of Felix, just wanted to.., really just come back to your level of confidence in providing a top-line readout from the study for the end of the year, and particularly wondering if there's any flexibility in including patients from the running portion in the primary endpoint efficacy analysis. And then secondly, as it relates to carousel. I'm wondering if you could just kind of help frame the primary CNS lymphoma commercial opportunity and what, Regulatory, Outlook might look like an indication. September 27, 2014, facilitator.

Good morning, good afternoon, thanks for taking the questions.

On helix or parts of the Felix just wanted to.

Uh huh.

Really just come back to your level of confidence in.

We're running a top line readout from this.

But at the end of the year, and particularly wondering if there's any flexibility in including.

Patients from the running portion in the primary endpoint efficacy analysis.

And then secondly, as it relates to carousel.

Wondering if you could just kind of help frame the primary CNS lymphoma commercial opportunity and what the regulatory.

Hum.

Outlook might look like and any indication in terms of.

Study size and endpoints that would.

Facilitator allowed for an approval thanks.

Christian Itin: All right. Well, thanks a lot, Eric. First off, kind of with the FELIX study and whether we would—the analysis would include the Phase 1b cohort of the study. Obviously, from a safety perspective, all the patients will be included as is normally done. From a statistical perspective, the data set that obviously will look at efficacy will be the Phase 2 portion only, which is the way that the trial was designed.

Alright, well, thanks, a lot Eric first off with the Felix study.

And whether we would do the analysis would include the phase <unk> cohort of the study.

And obviously from a safety perspective on all the patients will be included as is normally done from a statistical perspective, the data set that obviously will look at efficacy.

It will be the phase II portion only.

Christian Itin: And so the Phase 2 data set is the key data set from that perspective. With regards to the primary CNS lymphoma, we're looking into that opportunity, obviously, some initial sizing, etc. We think it is, you know, somewhere in the range between kind of the pediatric and the adult ALL opportunity. And when we look at the regulatory path here, or development path, I think if you do have a good level of activity and the national safety profile, that you should have an ability with a relatively compact trial to be able to actually drive towards a label. This is very difficult to treat the disease with very limited options once the patients have relapsed.

Which is the way that the trial was designed.

And so the phase II data set this to key dataset from that perspective.

With regards to the primary CNS lymphoma.

We're looking into that opportunity.

Obviously.

Some initial.

Sizing et cetera.

We think it is.

Somewhere in the range between kind of the pediatric and adult AML opportunity.

And when we look at the regulatory path here with development path I think if you do have a good level of activity in the.

The national safety profile that he should have an ability with a relatively compact trial.

To be able to actually drive towards the label. This is a very difficult to treat disease with very limited options lots of patients have relapsed.

A.R. Joseph: So there is likely an opportunity with a rather tailored or focused approach, but obviously those conversations obviously have not happened at this point in time with regulators, so this is just a general outlook, given the type of indication, the backdrop that you have with the current standard of care, and the incomparable settings of other rarer forms of oncology. Okay, thanks for taking the questions, Chris. Thanks a lot, Eric. Appreciate it.

There is likely an opportunity with a broader tailored focused approach.

Obviously, those conversations obviously happened what happened at this point in time with regulators. So this is just a general outlook given the type of indication the backdrop that he has.

With the current standard of care.

And comparable settings.

Sure.

Vera forums.

Uncollectible.

Bankruptcies.

Okay that makes sense, okay. Thanks for taking the questions Christian.

Thanks, a lot Eric I appreciate it.

Christian Itin: Thank you. And our next question comes from Ingrid Geffenhau from Kempen. Your line is now open. Hi, team. Hi, Christian.

Thank you.

And our next question comes from Ingrid <unk> from Kempen.

Your line is now open.

Hi, Tim Hi, Christian.

Ingrid Geffenhau: Good afternoon. I just wanted to follow up a little bit more on what we should expect for WALS 122 updates. So, you mentioned we should see some initial data at EHA and then perhaps some more data towards the end of the year. Can you just break down what kind of – are we looking probably at response rates at EHA and then a longer follow-up? Or will this first update already contain some information, some sort of couple of months follow-up in the first phase? Yes, so thanks for joining and greet. So in Ottawa 22, we did start that work at the very start of last year.

No.

I just wanted to follow up a little bit more on what we should expect for lots of 122 update.

And we should see some initial data at Okay, and then perhaps some more data.

And can you just breakdown what kind of.

Looking probably at least close rates I E.

I'll have a follow up or what is first update of any questions for me.

And that's sort of a couple of follow up and first nations.

Yes, so thanks for joining and great Southern Ottawa 'twenty, two we did start that work at the at the very.

Christian Itin: So we have patients obviously that have been treated. And by the time we get to the EHA, we'll have been treated and followed for 12 months, or maybe slightly more than that. But also the patients, you know, involvement kept going into sort of the early part of the first quarter this year. And also for those patients, we will have sort of just a limited follow up. So I think a few things to sort of kind of set expectations. First off, the patients that we've been treating in this particular trial are patients that are not eligible for Kunraya. I think that's important to keep in mind.

Start of last year. So we have patients obviously, that's being treated.

And by the time, we get to the HSA will have been treated and followed for for 12 months or may be slightly more than that but I'll save the patient enrollment.

Enrolment kept going into sort.

So to the early part of the of the first quarter. This year and also for those patients who will have sort of just the limited follow up.

I think a few things to sort of kind of set expectations first off the.

Christian Itin: So these are patients that you would not see in a CBRNA trial or you would not have seen and frankly are not commercially treated with CBRNA. So that's the first thing, and it also includes patients that may have failed after Chimraya. So this is a very tough patient population that we sort of included in this study. The first thing that we're obviously going to be looking at are number one, response rate, number two, the safety profile. Also, we had a very favorable safety profile with ovacell.

The patients that we've been treating in this particular trial are patients not eligible for can ride out there.

I think that's important to keep in mind. So these are patients that you would not see the cabana trial or you would not have seen in fact theyre not commercial they're treated with <unk>. So that's the first thing and it also includes patients that may have failed after come Ryan as well. So this is a very tough patient population that we sort of include.

In this in this study the first thing that we're obviously going to be looking at are number one.

Christian Itin: We want to see what the safety profile looks like with the second canaric aperture receptor included in the product. And the third area that I think is important is to get a feel for persistence. And from a fundamental question related to relapses and what might have driven relapses, whether any antigen loss driven relapses. Obviously, we will have a first view on that, but given the range of follow-up that I indicated to you before, that is probably still a bit premature to sort of have an absolutely conclusive answer to that particular question, and I think it will be the data by the end of the year that will give us, I think, a very good view on the impact of the dual-targeting approach on the potential for CD19 loss-driven relapses in those pediatric patients.

Response rates now, but to the safety profile.

So we had a very favorable safety profile with Ob Sal we wanted to see.

What's the safety profile looks like with the second generic aperture receptor included in the product at.

The third area that I think is important is to get a feel for persistence.

And.

From a fundamental question related to.

Relapses and what might have driven relapses whether in Yahoo.

<unk> loss driven relapses.

We will have a thirst you on that but given the range of follow up that I indicated to you before that is probably still a bit premature to sort of have absolutely conclusive answer to that to that particular question and I think it will be the data by the end of the year that will give us I think a very good view.

The impact.

Impacts of the dual targeting approach.

The potential for CD 19 loss.

Driven relapses in those pediatric patients. So the primary update I think it will be a bad basic activity.

Christian Itin: So the primary update, I think, at EHA will be about basic activity, clinical activity, safety, persistence profiles, and I think will start to give us a feel for the impact on potential relapse, but I think the more complete picture will be the one at the end of the year. Right, that's clear. And if I may just have a quick follow-up on that, what could be some of the reasons why these patients were not eligible for chemotherapy?

Clinical activity safety process.

Persistence profiles and I think we will start to give us a feel for the impact on AUM.

Potential relapse, but I think the more complete picture will be the one at the end of the year.

Okay, that's clear and if I may just have a quick follow up on that what could it be some of the reasons why these patients are not eligible for <unk> right.

Christian Itin: Well, there are a number of potential reasons. First off, obviously, if the patient's already failed, you can't get a second time on the product. So that's one reason. But then it's also depending on where the localization of the disease is. Or there may also be elements related to comorbidities that may actually exclude you from chiropractic treatment.

Well there are number of potential reasons first off obviously to the patients who have already failed you can't get a second time on the product. So that's one reason.

But then it's also depending on where the localization of the diseases.

Or there may be also elements related to Comorbidities that may actually exclude you from from Korea treatment. So those I think key parameters that I think are impacting its essence, it's being in a condition. That's just not conducive for.

Christian Itin: So those are, I think, key parameters that I think are impacting. It's being in a condition that's just not conducive for the current standard of, All right, that's clear. Thank you. Thanks a lot, Ingrid. And thank you, and I am showing no further questions. I would now like to turn the call back over to Dr. Christian Itin for closing remarks.

Sure for the standard for the current standard of care.

All right that's clear thank you.

Thanks, a lot and grid.

And thank you and I'm showing no further questions I would now like to turn the call back over to Dr. Christian Eitan <unk> for closing remarks.

Christian Itin: Thank you very much. Well, thanks to all for joining us. Obviously, great to connect, hopefully, in the upcoming month in person. I'm definitely getting ready for that, and I'd like to thank you all for the support. And we're looking forward to an exciting 2022. Completely, I've listed, putting aside everything that's happened in the political landscape and the economic landscape, I think, from an internal perspective, we're in an excellent space, and I think it has a lot of opportunity for news flow as we go through the course of this year.

Thank you very much well thanks, all for joining I'll say a race to connect hopefully.

In the upcoming months in person.

Late getting ready for that and I would like to thank you all for the support and we're looking forward to an exciting 2022.

Completely I've listed putting aside everything that's happened on the political landscape and economic landscape I think from an internal perspective, we are in an excellent space and I think has a lot of opportunity for news flow as we go through the course of this year and looking forward to keeping you updated alright. Thank you very much and see you soon bye bye. Thank you.

Operator: And looking forward to keeping you updated. All right. Thank you very much. And see you soon. Bye bye. This concludes today's conference call. Thank you for participating. You may now disconnect. [music]

This concludes today's conference call. Thank you for participating you may now disconnect.

Yeah.

[music].