Q1 2022 Autolus Therapeutics PLC Earnings Call

Emily Beynon: transcript Emily Beynon Ladies and gentlemen, thank you for standing by and welcome to the Autolus Therapeutics First Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

Ladies and gentlemen, thank you for standing by and welcome to the autos Therapeutics first quarter 2022 financial results Conference call.

Operator: After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press Star 1 on your telephone. If you require any further assistance, please press Star 0. Thank you. I would now like to hand the conference over to our speaker today, Olivia Manser, Director of Investor Relations. Thank you, Ren. Good morning or good afternoon, everyone.

At this time all participants are in a listen only mode. After the speaker presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone if you require any further assistance. Please press star zero.

I would now like turn the conference over to your Speaker today, Olivia Maxa director of Investor Relations. Please go ahead ma'am.

Olivia Manser: And thank you for joining us to take part in today's call on the operational highlights and financial results for the first quarter of 2022. I'm Olivia Manser, Director of Investor Relations. And with me today are Dr. Christian Itin, our Chief Executive Officer, and Dr. Lucinda Crabtree, 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. Please make sure you're familiar with our disclaimer, which is on slide two of the presentation.

Thank you Ryan good morning, or good afternoon, everyone and thank you for joining us to take part in today's call on the operational highlights and financial results for the first quarter of 2022.

Olivia months, the director of Investor Relations and with me today are Dr. Christian <unk>, our Chief Executive Officer, and Dr. Lucinda Crabtree, 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. Please make sure youre familiar with our disclaimer, which is on slide two of the presentation.

Olivia Manser: On slide three, you'll see the agenda for today, which is as follows. Christian will provide an overview of our operational highlights for the first quarter of 2022. Lucinda will then discuss the company's financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, of course, we will welcome your questions. Thank you, Olivia, and good morning to you all.

On slide three you will see the agenda for today, which is as follows Christian will provide an overview of our operational highlights for the first quarter of 2020 NUCYNTA will then discuss the company's financial results. The full Christian will conclude with upcoming milestones and any other concluding comments.

Finally of course, we will welcome your questions.

Christian Itin: Thank you for joining us. It's my pleasure to review our progress for the first quarter of 2022. Please move to slide four.

Thank you Andrea and good morning to you all thank you for joining US it's my pleasure to review our progress for the first quarter of 2022. Please move to slide four for those of you who are new to Atlas.

For those who know us without we are building a fully integrated car T company building on our broad platform of sales programs and technology to chocolate technologies, we're generating car T products that are tailored to the specific tumor setting.

Christian Itin: For those of you who are new to Autolus, and as a fresher, for those who know us well, we're building a fully integrated CAR T-COM. Building on our broad platform of self-programming technologies, we're generating CAR T products that are tailored to the specific tumor setting. Illustrating this approach are Obicel, with its focus on physiological engagement of leukemic cells, maximizing potency while improving safety and persistence, Auto4-5, with a unique targeting approach for T-cell lymphomas, and Auto6-NG, a CAR-T product candidate building on a clinically validated CAR-2GD2 and adding programming modules to render the CAR-T cells insensitive to checkpoint and TGS beta inhibition while increasing CAR-T cell persistence.

Illustrating this approach <unk> with its focus on physiological engagement of leukemic cells, maximizing potency, while improving safety and persistence over four five with a unique targeting approach for T cell lymphoma, and <unk> LNG a car T product candidate is building on a clinically validated car <unk> and <unk>.

Programming modules to render the car T cells insensitive to checkpoint on TGF beta inhibition, while increasing car T cell persistence for manufacturing, we're using a common platform.

Christian Itin: For manufacturing, we're using a common platform and process design principles to generate products that are highly active and persisting in patients. Our current operations for clinical trial supply is working in four shifts, seven days a week, in what we are anticipating to be very close to our commercial manufacturing model. The commercial manufacturing facility designed for 2,000 products a year is under construction in the UK, about a mile away from our clinical trial manufacturing site, and expected to be ready for GMP supply by the middle of 2023. Moving to slide five.

We're using the <unk> platform and process design principles to generate products that are highly active and persisting in patients.

Our current operations for clinical trial supplies working in four shifts seven days, a week and what we are anticipating to be very close to our commercial manufacturing model the.

The commercial manufacturing facility designed for 2000 products of the year is under construction in the U K about a mile away from our clinical trial manufacturing site and expect it to be ready for GMP supply by middle of 2023.

Moving to slide five.

Christian Itin: We had a successful quarter with OV-Cell clearing the pre-planned futility analysis in the FELIX trial and enrollment continuing to plan. In addition to the primary morphological cohort in the FELIX trial, we are expanding the MRD, or Minimal Residual Disease, cohort to up to 50 patients. In clinical practice, patients get evaluated on a regular basis for recurrence of disease, typically using flow analysis of their bone marrow. Indication of MRD levels, or minimal residual disease levels, of leukemia triggers treatment of the patients rather than waiting for full-blown relapse before starting treatment. This additional cohort does not impact our plant filing timelines, as the primary data will be based on the data from the morphological cohort.

We had a successful quarter with Ob self clearing the pre planned futility analysis of the Phoenix trial and enrollment continuing to plan.

In addition to the prime rate morphological cohort in the Phoenix trial, we are expanding the <unk> or minimal residual disease cohorts to up to 50 patients.

In clinical practice patients, who get evaluated on a regular basis for recurrence of disease typically using flow analysis of their bone marrow.

Indication of MRV levels of minimal residual disease levels of leukemia triggers treatment of the patients rather than waiting for full blood lead us before starting treatment.

This additional cohort does not impact our planned filing timelines as the prime rate data will be based on the data from the morphological cohort.

Christian Itin: With obtaining RMAT from the FDA, we have received preferred regulatory access for OBCell in all our key territories, the U.S., EU, and U.K. In addition, the EO granted also orphaned drug designation for OBCell, adding to the same designation we have received previously from the FDA. In the second quarter, we're looking forward to updates at EHA from our evaluation of opi-cell in non-Hodgkin's lymphoma and primary CNS lymphoma, and two oral presentations covering our initial evaluation of the dual-targeting OTA1-22 in children with ALL who are ineligible for chimeria therapy, and our dose escalation experience for OTA4 in T-cell lymphoma.

With obtaining our Matt from the FDA, we have received preferred regulatory access for Ob sell in all our key territories the U S EU and UK.

In addition, the EU granted also orphan drug designation for <unk> cel, adding to the same designation that we have received previously from the FDA.

In the second quarter, we're looking forward to update that EASA from.

Evaluation of <unk> in non Hodgkin's lymphoma, and primary CNS lymphoma, and two oral presentations covering our initial evaluation of the dual targeting Ottawa 'twenty two in children with <unk>, who are ineligible for <unk> therapy, and our dose escalation experience for order for T cell lymphoma and <unk>.

Christian Itin: In addition, the clinical phase I evaluation for auto VIII and relapsed refractory multiple myeloma started, and we are on track for auto VI MG to start a phase I in the second half of the year. Turning to slide six.

The clinical phase one evaluation for auto <unk> in relapse refractory multiple myeloma started and we are on track for <unk> to start a phase one in the second half of the year.

Turning to slide six.

Christian Itin: Here is a snapshot of our operational progress. As indicated, our new manufacturing facility in Stevenage is progressing well. During the quarter, Dr. Lucinda Crafty was appointed as Chief Financial Officer on the retirement of Andrew Oakley.

Here's a snapshot of our operational progress as indicated our new manufacturing facility in Stevenage is progressing well during the quarter. Dr. Lucinda Crabtree was appointed as Chief Financial Officer of the <unk>, Andrew Oakley and as we prepare for the potential launch of <unk>, Brent Rice was promoted to senior Vice President and Chief Commercial officer.

Christian Itin: And as we prepare for the potential launch of OBCell, Brent Rice was promoted to Senior Vice President and Chief Commercial Officer. As well as clinical progress, we continue to innovate with our cell programming platform, and earlier this week, Autolus announced the online publication of three abstracts, submitted to the American Society of Gene and Cell Therapy, ASGCT, to be held May 16 to 19 in Washington, D.C. The three abstracts focus on Autolus' modular approach to CAR T-cell programming.

Christian Itin: The abstracts involve, first, enhancing CAR T-cell persistence using a competitively active cytokine receptor, second, engineering of CAR T-cells to express a fast CD40 protein to increase its persistence and anti-tumor activity, and three, developing a minocycling-mediated protein-protein displacement platform to make cell therapies untunable with a commercially available and safe small molecule in a dose-dependent and reversible manner. Slide 7, we're jumping over and go directly to slide number 8. The focus is here on OBCell, and just to remind you, OBCell has a unique mechanism of action built on a highly specific engagement of CD19 coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated. This FAST disengagement is based on the FAST operator, the cat binder, and drives three key properties of OBCell.

As well as clinical progress, we continue to innovate with our cell programming platform and earlier this week <unk> announced the online publication of three abstracts submitted to the American Society of gene and cell therapy GCT to be held May 16 to 19 in Washington D C.

The three abstracts focused on almost modular approach to car T cell programming. The abstracts involved first enhancing car T cell persistence using a constitutively active cytokine receptor <unk>.

Second engineering of car T cells to express.

Fast CD 40 protein to increase its persistence and antitumor activity and three developing a minocycline mediated protein protein displacement platform to make cell therapies on tunable with a commercially available and safe small molecule in a dose dependent and reversible manner.

Slide seven we're jumping over and go directly to slide number eight.

The focus is here on <unk> and just to remind you <unk> has a unique mechanism of action built on highly specific engagement of CD 19, coupled with a fast release from CD 19 wants to kill of the leukemic cell has been initiated.

This fastest engagement this station of the fast off rate of the camp Binder and drive three key properties of Ob sale very high clinical activity paired with minimal toxicity at excellent persistence move.

Christian Itin: Very high clinical activity paired with minimal toxicity and excellent persistence. Moving to slide nine, there still remains a very high unmet medical need for adult ALL patients, with approximately 3,000 patients reaching the relapsed refractory stage of the disease that are residing in the U.S. and in the EU. While frontline high-dose combination chemotherapy enables about 90% of the adult patients to achieve complete remission, only about 30% to 40% will achieve long-term remission. Once patients are relapsed, they have a median overall survival of less than a year.

Moving to slide nine.

There still remains a very high unmet medical need for adult AML patients with approximately 3000 patients reaching the relapsed refractory stage of the disease that are residing in the U S and the EU, while strong client high dose combination chemotherapy enables about 90% of adult patients to achieve complete remission.

Only about 30% to 40% will achieve long term remissions.

Once patients that are relapsed they have a median overall survival of less than a year.

Christian Itin: Insight has become the standard of care for relapsed and refractory patients. However, most patients progress rapidly. More recently, Ticardus has been approved, showing a higher level of clinical activity, but also a significant increase in toxicity.

The insight that has become the standard of care for relapsed and refractory patients. However, most patients progressed rapidly.

More recently to Carlos has been approved showing a higher level of clinical activity, but also a significant increase in toxicity.

Christian Itin: When we look at slide number 10, This slide summarizes the key data we have shown to date for OBCell in ALL, which suggests that OBCell could be potentially a transformational therapy for adult patients with ALL. In the initial FELIX Phase 1b data presented at ASH at the end of last year, OBCR showed a favorable safety and efficacy profile consistent with the data we have collected prior in the old CAR-19 study in the same patient population.

When we look at slide number 10.

This slide summarizes the key data we have shown to date for Ob sale.

In ALLL, which suggests that <unk> could be potentially a transformational therapy for adult patients with AML.

Initial Felix phase one data presented at Ash at the end of last year <unk> sales showed a favorable safety and efficacy profile consistent with the data we have collected prior in the old car 19 study in the same patient population.

Christian Itin: We saw a high overall response rate and the duration of response from the Olcar-19 study remained highly encouraging, with morphological event-free survival for Urbicel of 46% at 24 months with a median follow-up of 29.3 months, and patients approaching up to 42 months of durability. We continue to see sustained ovocell persistence in those patients as well. And to remind you, ovocell has been granted orphan drug designation by the FDA for ALL, prime designation by EMA, ILAC designation by MHRA, and most recently, RMAT designation by the FDA, and as well as orphan drug designation by EMA as well.

We saw a high overall response rate and the duration of response from the old car 19 study remains highly encouraging with morphological event free survival for Ob sale of 46% at 24 months of median follow up.

24 months with a median follow up of 29 three months.

And patients approaching up to 42 months of durability.

We continue to see sustained Ob south assistance in those patients as well and.

And to remind you <unk> has been granted orphan drug designation by the FDA for ALLL Prime designation by EMA ILEC litigation NHRA and most recently, our Mac designation by the FDA and as well as orphan drug designation by email as well.

Christian Itin: Moving to slide 11, we're conducting the FELIX study with 100 patients in a morphological cohort, treating those patients at sites in the U.S., U.K., and in Spain. We expect to be fully roamed as we go through the course of this year. And as mentioned, expect to have initial data starting in the second half of this year with full data in the first half of next year. Switching gears and moving to slide number 13.

Moving to slide 11, we're conducting the Felix study with 100 patients in the morphological cohort treating those patients at sites in the U S U K and in Spain.

We expect to be fully rolling as we go through the course of this year and as mentioned expect to have initial data starting in the second half of this year with full data in the first half of next year.

Switching gears and moving to slide number 13.

Christian Itin: OBCell's unique profile means it could be applicable to a broad range of B-cell malignancies. We are evaluating the product outside of ALL in non-Hodgkin's B-cell lymphomas, including the typical follicular, DLD-CL, mantle cell and CLL indications, and expect multiple clinical readouts during the course of 2022. The first clinical updates will be in June at EHA, where we have readouts from a phase one study, an extension of the old CAR study in the non-Hodgkin's indications, as well as from a separate study, the so-called CARO cell study in patients with primary CNS lymphoma.

<unk> unique profile means it could be applicable to a broad range of b cell malignancies, we are evaluating the product outside of ALLL in hodgkins of B cell lymphomas.

<unk>.

Typical follicular <unk> mantle cell and <unk> indications and expect multiple clinical readouts. During the course of 2020 to the first clinical updates will be in June of DHA or behalf Readouts from our phase one study and extension of the old car study in the non Hodgkin's indications as well as from a set.

What started the so called Carousel study in patients with primary CNS lymphoma.

Christian Itin: On slide 14, on the right-hand table, we provide a quick summary of the basic experience that we have to date with OBCell and pediatric ALL patients in the so-called CAR-PAL study. The fundamental finding was that we have excellent activity without high-rate cytokine release syndrome, but we did see about half of the patients relapse due to antigen loss of CD19. That is why we went back and built on this favorable profile of Robicel that we have seen in kits, adding a highly potent CD22 card to create a product called AutoOne Slash 22.

On slide 14 on the right hand.

Table, we provide a quick summary of the basic experience that we have today for Adobe sell in pediatric AML patients in the so called car pallet study the fundamental finding was that we have excellent activity without high grade cytokine release syndrome, but we did see about half of the patients lead ups due to antigen loss of CD 19.

That is why we went back and built on this favorable profile our royalty sale that we have seen and kits.

<unk>, a highly potent CD 22 car to create a product called Autobahn slashed 22.

Christian Itin: We will have an oral presentation at EHA of the Phase I data for Auto I-22 in pediatric ALL patients that were ineligible for chimeria therapy. Moving to slide 16 to talk more broadly about our technology base. Autolus is a wide range of technology covering mostly cell programming modules and product candidates.

Well as an oral presentation at <unk> of the phase one data for auto loans and 22 in pediatric AML patients that were ineligible for <unk> therapy.

Moving to slide 16 to talk more broadly about our technology base.

Although this is a wide range of technology, covering mostly cell programming modules and product candidates with over 100 patent families of the prosecution we have a very significant technology treasure chest that we are building on.

Christian Itin: With over 100 patent families under prosecution, we have a very significant technology treasure chest that we're building on. Three new cell programming approaches will be presented at ASGCT annual meeting in mid-May, which showcase our industry-leading T-cell programming technology. Key areas covered by our cell program, MOTIV, cover selecting selective targeting of cancers, controlling CAR-T cell activity, shielding CAR-T cells from the cancer microenvironment, as well as the patient's immune system, and enhancing CAR-T cell persistence, as well as attracting the support of the patient's own immune system in the fight against the cancer. Moving to slide 17.

Christian Itin: Here, we have tabulated next-generation programs alongside the progress in the clinic. Most advanced is Order 4, our program to address T-cell lymphomas. Order 5 is the FISTA program to Order 4, and following Order 4 into clinical development. Both programs are run internally.

<unk> new cell programming approach is what we presented at <unk> annual meeting in May, which showcase our industry, leading T cell programming technologies key areas covered by our sales program.

Cover at selecting selective targeting of cancers controlling car T cell activity shielding car T cells from the cancer microenvironment as well as the patient's immune system and enhancing car T cell persistence as well as attracting the support of the patients own immune system in the fight against cancer.

Moving to slide 17 here, we have tabulated next generation programs alongside the progress in the clinic. Most advanced is order for our program to address T cell lymphomas order five as assistant program to order four and following order four into clinical development.

Both programs are run internally in collaboration with our academic partner UCL, We have moved auto eight into the clinic into the clinic in a phase one clinical study in multiple myeloma patients are working with <unk> to get into the clinic second half of this year targeting neuroblastoma solid tumors in children.

Christian Itin: In collaboration with our academic partner, UCL, we have moved Auto-8 into the clinic in a phase one clinical study in multiple myeloma patients. And we're working on Auto-6-NG to get into the clinic second half of this year, targeting neuroblastoma, a solid tumor in children. Turning to slide 18, I'll give you further information about Auto IV. We're actively exploring T-cell lymphoma, which is an aggressive disease with very poor prognosis for patients. The primary challenge has been to find a structure or target on the surface of T-cells that would allow you to target the T-cell lymphoma without at the same time targeting all T-cells together.

Turning to slide 18, I will give you further information about auto for.

We are actively exploring T cell lymphoma, which is an aggressive disease with very poor prognosis for patients with primary challenge has been defined a structure or targets on the surface of T cells that would allow you to target the T cell lymphoma without at the same time targeting all T cells together.

Christian Itin: And of course, what that means is that you need to have a target that allows you to get the lymphoma, leaving the T-cells behind and with that preserving immunity in these patients. Auto4 is targeting a structure called TRBC1, and it fits the program Auto4, a structure TRBC2. Both structures are related, they're a part of the constant domain of the T-cell receptor beta chain, and are coming basically available in T-cells in either one or the other isoform.

And of course, what that means is that you need to have a target that allows you to get there.

The lymphoma, leaving to T cells behind and with that preserve immunity in these patients <unk> is targeting a structure called <unk> and it's just a program order for a structure TWC to both structures are related that are part of the constant domain.

Off the T cell receptor beta chain and are coming are basically available in T cells in either one or the other isoforms.

Christian Itin: Those targets are novel, and we obviously are planning to show first data in an oral presentation at EHA for Auto IV from our dose escalation experience in phase one. With that, I'd like to actually hand over into the financial section and hand over to Lucy who's moving to slide, Thanks Christian and good morning or good afternoon to everyone. So moving to slide 20, it's my pleasure to review our financial results for the first quarter to March 31st, 2022.

Those targets are novel and we obviously are planning to show first data in an oral presentation at EOG for order for from our dose escalation experience in phase one.

With that I'd like to actually hand over into the international section and hand over to Lucy Who's moving to slide number 20.

Thanks, Christian and good morning, or good afternoon to everyone.

Alright.

See slide 20, it's my pleasure to review our financial results for the third quarter till March 'twenty.

2022.

Christian Itin: On the journey to transitioning Autolus into a fully integrated CAR T company, we continued in the first quarter of 2022 to focus our research and development efforts on our lead product, OBCell, and our pipeline assets addressing cancers with limited treatment options. So starting with R&D expense, for the three months ended March 31st, 2022, research and development expenses increased to $34 million from $30.7 million for the three months ended March 31st, 2021.

The journey to transition useless interestingly integrated coffee company, we continue to Incent creature.

Research and kind of an effort on our lead product.

And our pipeline assets.

Limited treatment option.

Christian Itin: Cash costs, being the biggest component of our R&D expense, were relatively flat at $30.6 million this quarter, from $30.7 million for this quarter ended March 31st, 2021. The small decrease in research and development cash costs to the tune of $0.1 million consisted primarily of a $2.8 million decrease in compensation and employment related costs, which was due to a combination of lower retention, severance payments and the timing of salary mix of new employee hires.

So starting with R&D expense for three months ended March 31st two.

<unk> research and development expenses increased to <unk> million.

<unk>.

From $37 million for the three months ended March 31st 2021.

<unk> being the biggest component of our R&D expenses were relatively flat at $36 million this quarter from $37 million.

For the quarter ended March 31st 2021.

The decrease in research and cash cost of between $1 million consisted primarily of.

$2 8 million a decrease in compensation and employee related costs, which was due to a combination of net retention and severance payments.

Timing of kind of the mix pretty eyes.

Lucinda Crabtree: A $0.9 million decrease in facilities costs related to the termination and exit of our U.S. manufacturing facility in the prior year and shift in our manufacturing strategy, and a $0.2 million decrease in research and development costs related to sales logistics. These decreases in R&D cash costs were offset by an increase of $2.9 million in clinical costs and manufacturing costs primarily related to our OBCell clinical product, $0.8 million increase in legal fees and professional consulting fees in relation to our research and development activities, and a $0.1 million increase related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations.

$9 million decrease in costs related to the termination and exit the year.

<unk> E and shifting our manufacturing strategy and at no point $2 million, a decrease in research and patent costs related to logistics.

Decreases in R&D cash costs were offset by an increase of $2 $9 million in clinical costs and manufacturing costs primarily related to.

Clinical product.

$8 million increase in legal fees and professional consulting fees in relation to an essential activity.

$1 million increase related to information information technology infrastructure and coaching and support for information systems related to the conduct of clinical trials manufacturing operation.

Lucinda Crabtree: Non-cash costs increased to $3.4 million for the three months ended March 31, 2022, from $36,000 for the three months ended March 31, 2021. The increase is primarily attributable to an increase of $3.1 million in share-based compensation expense included in R&D expenses as a result of the retention of employees post the reduction of workforce that was implemented during the three months ended March 31st, 2021. In addition, depreciation and an amortization expense increased by $0.3 million.

Noncash costs increased to $3 $4 million for three months ended March 30, <unk> 2000.

And tonnage.

The three months ended March 2021.

The increase is primarily attributable to an increase of $3 $1 billion. The share based compensation expense included in R&D expenses as a result of their attention. Please place the reduction of workforce that was implemented during the three months ended March 2000.

In addition, depreciation and amortization expense increased by $2 million.

Lucinda Crabtree: Just touching on the GNA side, expenses decreased by $0.7 million to $8 million for the three months ended March 31, 2022, from $8.7 million for the three months in the first quarter of the prior year, of which GNA cash costs, which excludes depreciation and amortization, as well as share-based compensation, decreased by $0.6 million to $7 million. All in all, including grant income and net total other expense, with the largest component being the interest expense of $1.8 million, which corresponds to the liability related to sales of future royalties and sales milestones, which arose upon entering into the Blackstone Strategic Collaboration, we ended the first quarter 2022 with a net loss on a pre-tax basis at $42.7 million versus $39 million in Q1 2021.

Just touching on the G&A side expenses decreased by <unk>.

$7 million.

$8 million for the three months ended March 30.

2019 from $8 $7 million for the three months.

Andy.

First quarter of the prior year.

G&A cash costs, which exclude depreciation and amortization share based compensation decreased by <unk> six.

$6 million.

$70 million.

All in all including on income net total other expense with the largest component and the interest expense $1 $8 million, which corresponds to the liability related to future booties, it sounds like things, which everybody's upon entering into the Blackstone Blackstone strategic collaboration we ended the first quarter 2022, with a net loss on a pre tax basis.

At $42 $7 million 30.

$39 million in Q1 2021.

Lucinda Crabtree: Although income tax benefits related to qualifying research and development expenditures continue to play a role as a source of additional cash, and the tax credit for the three months ended March 31, 2022, amounted to $5.6 million versus $5.7 million in the prior year quarter. All in all, this resulted in net loss attributable to ordinary shareholders of $37.1 million for the three months ended March 31, 2022, versus $33.3 million in the prior year quarter.

On the income tax benefits related to quote find research and development expenditures continued to play a role as a source of additional cash and the tax credit for the three months ended March 31st 2020 amounted to $6 million versus $5 $7 million in the prior year quarter.

This resulted in net loss attributable to ordinary shareholders and $37 $1 million and three months ended March 'twenty two.

Thank you $3 $3 million in the prior year quarter.

Lucinda Crabtree: This, in turn, gave a basic and diluted net loss per ordinary share for the three months ended March 31st, 2022, totalling 41 cents, compared to a basic and diluted net loss per ordinary share of 53 cents for the three months ended March 31st, 2021.

This in turn gives a basic and diluted net loss per ordinary share for three months ended March towards <unk> totaling Portugal.

Compared to basic and diluted net loss per ordinary share and 53.

And at March.

'twenty one.

Lucinda Crabtree: Finally, we ended the quarter with a cash position at $268.6 billion, and consistent with prior guidance, point to a cross-funding cash runway into 2024, assuming receipt of Blackstone Marlstone. And now let me turn back to Christian to give you an overview of the pipeline and a brief outlook on expected milestones. Christian.

Finally, we ended the quarter with a cash position.

<unk> hundred 68 $6 billion.

I can point to of course, losing cash runway into 2020, assuming proceeds nothing.

And now let me turn it back to Christian.

The pipeline and proof point as.

Chris.

Christian.

Christian Itin: Thanks, Lucy. Moving to the final slide, number 22. Finally, next steps. We believe we have an exciting year ahead of us, with OBCell running through the pivotal study in adult ALL, delivering initial clinical data from this pivotal study later this year, and full data expected in the first half of 2023. We plan to provide clinical updates from four of our programs at EHA this June. And this is in addition to progress across the pipeline that we alluded to, as well as we went through the presentation, in particular with obviously also looking at Auto6NG, expecting to enter the clinic in the second half of this year. Finally, as a result of our collaboration with Blackstone, we're in a strong financial position with cash runway, including project financing payments from Blackstone into 2024.

Thanks Lucy.

Moving to the final slide number 22.

Finally next steps, we believe we have an exciting year ahead of us with Ob sales running through the pivotal study in adult ALLL delivering initial clinical data from this pivotal study later this year and full data expected in the first half of 2023.

We plan to provide clinical update from four of our other programs from four of our programs at EAA. This June .

And this is in addition to progress across the pipeline that we alluded to as well as we went through the presentation and particularly with obviously also looking at almost six mg expecting to enter the clinic in the second half of this year finally, as a result of our collaboration with Blackstone, We're in a strong financial position with cash runway, including project side.

Nancy payments from Blackstone into 2024 with that we're happy to take questions.

Operator: With that, we're happy to take questions. As a reminder, to ask a question, you will need to press star 1 on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound. Once again, that's star one on your. Your first question comes from the line of Matt Phipps from William Blair. Your line is open.

As a reminder to ask a question you will need to press star one on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key once again Thats star one on your Touchtone telephone.

First question comes from the line of Matt.

Blair Your line is open.

Matt Phipps: Good morning, Christian, or well, I think it's not morning anymore there, but thanks for the call. I was wondering, Christian, if you could maybe help us set the stage a little bit for the Auto IV results. We've seen other CAR targets against T cell malignancies, such as CD5, CD7, do see some responses. A lot of patients maybe go to transplant. But I guess, you know, are you expecting a lot of patients in the Auto IV trial to go on to transplant if they do achieve a complete response? And then I assume also looking at things like viral infections will be another key data point for this program in the first update. Good morning, Matt.

Good morning Christian.

And it's about working with it but thanks for the call.

I was wondering Christian if you could maybe help us set the stage a little bit for the auto for results.

<unk> seen other car targets because T cell malignancies, such as <unk> 587, do you see some responses.

Basically we've got a transplant.

But I guess.

Are you expecting a lot of patients than the auto for trials to go on to transplant, if they do achieve a complete response.

I'm also looking at things like viral infections will be another key data point for this program in the first update.

Christian Itin: Thanks for joining. Very good question. So, as you pointed out, obviously, T-cell lymphoma is a very tough disease to go after. There are a number of approaches that have been tried. What you refer to, programs like CD5 or CD7, have sort of a limited application. CD7 is mostly present on acute leukemia, T-cell acute leukemia, rather than T-cell lymphoma. It's only a very small subset of T-cell lymphomas that carry CD7.

Good morning, Matt Thanks for joining a very good question. So as you pointed out obviously.

T cell lymphoma, it's a very tough disease to go after a number of approaches that have been tried.

What you referred to programs like <unk>, five or <unk> seven.

Limited application.

<unk> seven is mostly present on that.

Acute leukemia T cell acute leukemia, rather than T cell lymphoma.

Christian Itin: When you look at CD5, that's a general activation marker for T-cells. So, any T-cell that gets activated, including our CAR T-cells, would actually become CD5 positives, which obviously creates a number of challenges. And if you go after more general targets, like CD4, as an example, you run the risk that you're actually eliminating the compartment as you're trying to attack and trying to tackle the disease itself with consequences for the patient's ability to actually maintain a healthy T-cell mediated immune response.

It's only a very small subset of T cell lymphoma with Caris <unk> seven when you look at.

<unk> five thats, a general activation market for T cell, so any T cell that gets activated including our car T cells would actually become Sydney, five positives, which obviously creates a number of challenges.

If you go after more general targets like <unk> as an example.

Run the risk that you're actually eliminating the compartment as youre trying to attack and trying to tackle the disease itself with consequences for the patients ability to actually maintain a healthy T cell mediated immune response.

Christian Itin: So, what we're looking to do with Auto IV and then also with the sister program, Auto V, is really targeting a subset on the one hand, the disease itself, but then also only a subset of healthy T-cells so that at least half of the remaining T-cells, in theory, would not be targetable with the CAR T and with that sustained T-cell mediated response over time. What we're looking to do and what we've been doing in the trial that we're going to be updating on is obviously dose escalation. It's a wide range of doses, starting at very low levels to elevated levels.

So what we're looking to do with order for and then also assisted program OTO five is really targeting.

A subset.

On the one hand, the disease itself, but then also only a subset of healthy T cells. So that at least half of the remaining T cells in theory would not be targeting <unk>.

With it with a car T and with that sustained T cell mediated response over time.

What we're looking to do and what we've been doing in the trial that we're going to be updating on this obviously dose escalation. It's a wide range of doses starting at very low levels to elevated levels.

Christian Itin: And what we're looking to see are several points. Number one, one to understand the safety profile. Number two, obviously, do we have an ability to induce complete remissions in these patients? And number three, do we see any evidence that we're impacting the broader T-cell compartment in these patients, which obviously would be a concern from an overall safety perspective. As we're in a dose escalation, we have varying degrees of follow-up and we'll need to see and gain more experience to see whether indeed some of these patients may need to receive transplant in the future or whether the therapy on its own will be sufficient to sustain long-term remissions. That is too early to tell, but I think we're going to get a very good understanding. It's a novel target.

And what we're looking to see.

Several points number one to understand the safety profile.

Number two obviously do we have an ability to induce complete remissions in these patients.

Number three do we see any evidence that were impacting the broader T cell compartment in these patients, which obviously would be.

Concern from an overall safety perspective.

As we're in the dose escalation, we have varying degrees of follow up.

And we'll need to see it gain more experience to see whether indeed.

Some of these patients may need to receive transplant in the future or whether this therapy on its own both the sufficient to sustain long term relations that is too early to tell but I think we're going to get a very good understanding. It's a novel targets novel approach. It's first in man experience and I think it will give us a very good initial expense.

Christian Itin: It's a novel approach. It's first-in-man experience, and I think it'll give us a very good initial experience and understanding of the potential of this approach. Thanks, Christian.

And understanding.

The potential of this approach.

Christian Itin: And if I could ask one additional question, the recent data from from Stanford Group at ACR with a GD2 CAR, you know, showed some encouraging results in a, Tough glioma setting, but also did use. ICD infusions. I'm wondering if that's something you would look at, any kind of intracranial infusions with autosex programs. Right. So the specific indication that the Stanford group went after is a form of a glioma, which is obviously a cancer that is localized in the brain.

And then if I could ask one additional question the recent data from from Stanford Group.

With a GDP two car.

Showed some encouraging results.

Technically all of a sudden but also did use.

ICD infusions I'm wondering if that's something you.

I would look at any kind of intracranial infusions.

Six program.

So the specific indication that Stanford group went after is a form of <unk>.

<unk>, which is obviously.

Cancer that is localized in the brain.

There are various ways and how we can think about accessing debt whether you access.

Christian Itin: And there are various ways in how we can think about accessing that, whether you access the brain through an infusion of CAR T-cells into the bloodstream and then have the CAR T-cells migrate across the blood-brain barrier into the brain and then have an ability to target the glioma.

The brain through an infusion of car T cells into the blood stream and then have to the car T cells migrate across the blood brain barrier into the into the brain.

And then have an ability to target glioma. That's one approach it can take work. The SaaS. The team has done is take the ultimate approach, it's literally going directly into the brain.

Operator: That's one approach you can take. And what the Stanford team has done is take the alternate approaches, literally going directly into the brain and, frankly, delivering product directly onto the lesion in those patients. Obviously, that's an approach that's workable, as we're seeing, obviously, and we'll also have data for OBCL and primary CNS lymphoma, where we also do approach the dosing from the systemic side, so from the blood side. And I think we can start to see, you know, I think that both rights are possible and are usable.

Frankly delivering product directly.

Onto the lesion.

In those in those patients.

Obviously, that's an approach that is workable.

We're seeing obviously and we'll obviously have data for Ob sale of primary CNS lymphoma, where we also do approach.

The dosing.

From the systemic sites from the blood side.

I think we can start to see I think that that both rates are possible and are usable.

Operator: For our own TD2-CAR program, we would not envisage a...we would envisage a normal systemic approach, because the disease we're treating, uroblastoma, is a kidney-associated tumor that we can actually very well access just through standard administration into the bloodstream. Thanks, Matt.

For our own TV two car program noninvasive.

A.

We would envisage a normal systemic approach because the disease are treated in Europe last summer.

Kidney associated tumors that we can actually vary bell actions, that's true standard administration into the bloodstream.

Okay.

Thanks, Matt.

Nick Abbott: Your next question comes from the line of Nick Abbott from Wells Fargo, your line. Oh, good morning. Thank you for taking my question. Yes, lots of things going on here, team.

Your next question comes from the line of Nick Abbott from Wells Fargo. Your line is open.

Oh good morning, Thanks for taking my question.

Yes lots of things going on here team.

Nick Abbott: And I apologize that I had to join the call late, but the first question is on what we might expect as a benchmark for primary CNS lymphoma. The MGH group just published in Blood some experience with Axacel. I think it was quite surprising, to me at least, with low-grade ICANNs, grade 1, grade 2, grade 1 CRS, and they reported a 60% response rate, 50% CR, with three of those complete responses showing significant durability of greater than six months at least.

And I apologize because I had.

During the call late but the first question is on on.

What we might expect as a benchmark for primary CNS lymphoma. The MGH group just published in blood some experience with Axa fell.

I think it was quite surprising to me at least was.

Low grade ICANN as grade one grade two.

Greg one Crs.

Reported a 60% response rate 50% CER.

Three of those.

Responses showing significant durability of greater than six months late so I'm wondering what we should be expecting for.

Pardon me CNS lymphoma, and whether you think this is a good benchmark.

Christian Itin: So I'm wondering what we should be expecting for... Primary CNS Lymphoma and whether you think this is a good benchmark. So, first of all, thanks for joining, Nick. On primary cyanosis lymphoma, what we're planning to do is provide, obviously, initial information on the early patients that we have in the trial. Obviously, that gives us, you know, a view, an initial view. I don't think we're at the point where we're going to be, I think where we can easily benchmark, given the number of patients that we're able to report on that.

So first of all thanks for joining.

On the on.

Primary CNS lymphoma, which we're planning to do is provide.

The initial information on the early patients that we have in the trial.

Obviously that is.

It gives us.

An initial view I don't think Rep point, where we're going to be I think what we can easily benchmark given the number of patients that were able to report on at this point I think in general seeing.

Christian Itin: I think in general, seeing, you know, a give or take 50% CR rate in these patients, I think is very encouraging. And I think it certainly would be a good outcome for patients with this disease, considering also frankly the lack of any suitable other options. Okay. Thanks, Christian.

No.

Give or take 50% CR rate in these patients I think is very encouraging.

And I think it's a start.

And that would be a good outcome for patients with this disease. Considering also factors the lack of any suitable lots of options.

Nick Abbott: And then I noticed that you mentioned that auto aid has been.., initiated now. Do you think you'll have, when do you think you'll be able to present some initial data from that trial? I would assume this is a phase one clinical trial, and I would assume that we'll have to look at the second half of next year for early clinical data. Okay, great. Thanks a lot, Christian. Thanks a lot, Nick. Appreciate it.

Okay. Thanks, Kristen and then.

I noticed that you have.

You mentioned that.

Also it has been.

Initiated now.

Do you think Youll have when do you think you'll be able to present some initial data from that trial.

I would assume this is a phase one clinical trial.

I would assume.

You have to look at the second half of next year.

Early clinical data.

Okay, great. Thanks, a lot Christian.

Thanks, a lot make I appreciate it.

Operator: Your next question comes from the line of Mara Goldstein from Missouho. Great. Thanks so much for taking the question. I wanted to ask just on the.., on the Auto4 program.

Your next question comes from the line of Mara Goldstein from Mizuho. Your line is open.

Great. Thanks, so much for taking the question I wanted to ask just.

On the.

On the auto program.

Mara Goldstein: I think the upper dose limit has been raised there to 900 million cells. And can you talk a little bit about that and that dynamic? And then lastly, just on Obacel and the new MRD cohort, maybe you can talk a little bit about what are the challenges in that cohort and why Obacel may be appropriate there. Yes, happy to do that, Mara.

I think the.

Upper dose limit has been raised 900 million telecom can you talk a little bit about that in that dynamic and then lastly, just on <unk> and the new MRV cohort, maybe you can talk a little bit about.

What are the challenges in that cohort in <unk>.

<unk> may be appropriate there.

Christian Itin: Thanks for joining. So first, with regards to Auto IV, as I indicated, Auto IV, we ran through a dose escalation, started at relatively low levels. The initial dose that we had in, I think, highlighting clinical trial knockoff was 225 million cells, and we created an opportunity to go further than that. We will obviously provide an update on kind of the upper dose range that we went to. We didn't go all the way to 900, and you'll see, obviously, overall, kind of the efficacy and safety profile that we're starting to achieve at the higher dose level.

Yes happy to do that thanks for joining.

So first with regards to auto for as I indicated on the floor.

And through a dose escalation.

With relatively low levels.

Initial dose that we had in I think highlighting clinical trial Doc off was at $2 25.

Indian sales and.

We created an opportunity to go further than that.

We will obviously provide an update on kind of the Alfa dose range that we went to we didn't go all the way to 900.

And Youll see obviously overall is kind of the year.

<unk> safety profile that we're starting to achieve at the higher dose levels.

Christian Itin: With regards to the MRD cohort for OBCell, I think the importance of the MRD cohort is several-fold. First off, we do have a bit of a discrepancy between the regulatory data package that we need to get to an approval versus the data and the treatment that we actually—treatment algorithm that we do see taking hold at clinical centers. Most clinical centers, also based on the experience with plant cycle in patients with mineral residual disease, are preferring to start treating patients when they have a first inkling of the disease coming back.

With regards to the <unk> cohort for <unk> I think the importance.

Also we have our day cohort is several fold first off.

We do have a bit of a discrepancy between the regular.

Regulatory data package that we need to get through the approval.

First is the data and the treatment.

That we actually treatment algorithm that we do see.

Taking hold of clinical centers, most clinical centers also based on the experience with late cycle in patients with minimal residual disease.

Preferring to start treating patients where they have a first inkling of the disease coming back.

Christian Itin: And what normally happens with these patients is that you actually take—at periodic intervals, you take bone marrow biopsies. You run those bone marrow biopsies typically on flow, and you look for the presence of leukemic cells. The sensitivity of that methodology gives you somewhere in the range of 10 to the minus 4, 10 to the minus 3 resolution very reliably, and that compares to a 5 percent level that you would have to cross the boundary to become a morphological patient.

And what normally happens with these patients is to actually take.

At periodic intervals, who take bone marrow biopsies you run those bone marrow biopsies typically on flow and you look for.

The presence of leukemic cells.

Sensitivity of that methodology gives us somewhere in the range of 10 to the minus 4% to the by history.

Resolution very reliably.

And that compares to a 5% level that we would have to cross the boundary could become a morphological patients. So you have to discover and do you actually look at that in the clinic for these patients. If you look for these low levels of disease. In these patients now when you find that the patient actually does have low level disease.

Christian Itin: So you do discover, and you actually look at that in the clinic for these patients. You look for these low levels of disease in, Now, when you find that the patient actually does have low-level disease, typically you would not want to wait for that patient to progress to full-blown disease before you start treating, because there are two things that happen.

Typically you would not want to wait for that patient to progress to full blown disease before you start treating because there are two things that happened on the one hand, you have obviously a lot more tumor burden, which means you have a higher.

Christian Itin: On the one hand, you have obviously a lot more tumor burden, which means you have a higher—typically, when you intervene with any kind of therapy, a higher amount of toxicity, but you also have a lower probability of actually inducing a lower-term benefit in these patients. So it's both a safety from a safety and a efficacy side not desirable from a patient—from a physician's perspective to wait. And so what we're doing with the MRD cohort is really alongside the data set that we need to have in place to support the regulatory approval of the product.

Typically when you need to be with any kind of at the higher amount of toxicity, but you also have a lower probability of actually inducing a longer term benefit in these patients. So it's both the safety from a safety and efficacy side not desirable from a patient from a physician's perspective to wait.

Christian Itin: We're also looking to generate data that actually support and basically characterize the profile of the product against patients and patients with lower disease burden, which is closer to what actually we're seeing in many clinical practices, both in the US and in Europe, the situation is moving. So that's sort of the backdrop to what we're doing in the work with the MRD cohort. All right. Thanks so much.

And so what we're doing with the Mach E cohort as data alongside the market. The data set that we need to have in place.

To support the regulatory approval of the product. We're also looking to generate data that actually.

Imports basically characterize the profile of the products against patients and patients with lower disease burden, which is closer to what's actually we're seeing in many clinical practices. Both in the U S and in Europe . The physicians moving too. So that's sort of the backdrop to what were doing and to work with the <unk> cohort.

Alright, thanks, so much.

Thank you.

Okay.

Operator: Thank you. Your next question comes from the line of Gil Blum from Needham. Your line is open.

Your next question comes from the line of skilled bluhm from Needham Your line is open.

Yes.

Gil Blum: Good morning, everyone, and thanks for taking our questions. Maybe a clarification on the MRD population. So are current approved CAR T's used in patients that are MRD positive? Good morning, Gil.

Good morning, everyone and thanks for taking our questions. So maybe a clarification on.

The population.

No.

Current of Peru.

Car Ts use in patients that are positive.

Christian Itin: Thanks for joining. What we do see is that certainly in the pediatric patients that the physicians have been moving to treating the kids very early on, typically when they have minimal residual disease. So that's an observation that we certainly see across, I think, many of the centers within this disease setting and where you would start using a particular chimeraia very early on. I think in general there is a view that you would like to actually treat early and I think the best visibility at this point we have from the pediatric population, because it's also where obviously the CAR-T therapy is probably most established. Okay, thank you. And maybe I have a question on... Sorry, I have a second item.

Good morning, Gil Thanks for joining what we do see is that certainly in the pediatric patients that.

The physicians have been moving.

Treating the case very early on typically when they have minimum residual disease.

An observation that we certainly see in across I think.

Any of the centers.

Within this disease, setting and where you would start using a particular <unk> very early on.

In general there is a view that you would like to actually treat early.

And I think the best visibility at this point, we have from the pediatric population because it's also where obviously the car T therapy is probably most established.

Thank you.

And maybe that's a good question.

The second item.

Sorry.

Christian Itin: The second part, obviously, of the answer is that the experience that physicians have gained with BlinkSite, also with adult patients, also moves quite significantly towards patients with mineral residual disease, rather than waiting for the patients to develop full-blown morphological disease. The difference in response rate is quite significant. You have about 43% to 44% CR rate in a morphological disease of BlinkSite, but you do have about 78% CRs, molecular CRs, if you go into the MRD population, for PlainSight.

Sorry, the second part obviously of the answer is that the.

The experience that physicians have gained with <unk> also with adult patients also moves quite significantly towards patients with minimal residual disease, rather than waiting for the patients to develop full blown.

Full blown morphological disease. The difference in response rate is quite significant you have about 43% to 44% CR rate.

The morphological disease or clean cycle, but you do have <unk>.

78%.

A CR.

C a R.

Molecular Crs if you go into the MLP population.

Propylene side.

Christian Itin: All right, so it makes sense to have earlier treatments. Maybe a question, Otto122, you said chimeria ineligible. Can you remind us if any of these patients that are being enrolled have experienced heart disease in the past? Right, so Auto One 22, obviously, which is a dual targeting car, we treat it in our in the phase one experience now, kids that are ineligible for Kymriah, and you can be ineligible for Kymriah for a set of reasons.

Alright, so it makes sense to have earlier treatment.

Maybe a question auto $1 22.

You said come Brian eligible can you remind us of any of these patients that are being enrolled have experienced our teeth in the past.

Right, So Ottawa plenty to obviously, which is a dual targeting car.

The.

Treated in our interface lawn experience now cases are ineligible for <unk> and it can be ineligible for Brian or for a set of reasons. One is that you already have Kim Ryan and you cannot get a second dose.

Christian Itin: One is that you already have Kymriah and you cannot get a second dose. And that is obviously part of the population that we have enrolled. Secondly, it can be that the disease is localized in an area where you actually have to exclude patients from the treatment of Kymriah, and in particular, a localization obviously would be CNS localized disease.

And that is obviously part of the population that we have involved.

Secondly, it can be that the disease is localized.

In an area, where you actually have to exclude patients from the treatment of <unk> in particular, our localization obviously would be CNS local is localized disease.

Christian Itin: So it's typically related to either prior therapy with Kymriah and not being eligible anymore for a second go, or having disease that is basically extramedullary disease, disease outside of the marrow, that actually would disqualify you from being offered Kymriah as a therapeutic option. Alright, so maybe a follow-up there. Will the presented data be stratified based on patients who are, you know, experienced previous CAR-T therapy or, It's more of a like a... Next. next.

So it's typically related to either prior therapy with Cambria and not being eligible anymore for a second go or having disease studies.

Basically extra medullary disease disease outside of the marrow that actually.

Disqualify you from bidding.

Offer to provide us a therapeutic option.

Alright, so maybe a follow up there.

Presented data be stratified.

Based on patients who are experienced previous car T therapy or.

It's more of a knife.

Mixed bag.

Christian Itin: We'll have both categories of patients. It's a phase one experience, so it's a limited number of patients. But we have both patients who either have relapsed post-chemorrhagia or patients that have disease outside of the normal localization. All right. And maybe a last one.

We'll have we'll have both categories of patients. It's obviously, it's a phase one experience. So it's a limited number of patients, but he has both patients who have either.

<unk>.

Kim Ryan or patients that have disease outside of the normal loan coordination.

Alright.

Christian Itin: I know you guys show are showing a bunch of the really interesting new technologies. Modular Technology is coming out of ASGCT, considering the current... Laser focused on Obacel. Are you guys considering out licensing some of these technologies to other firms? I think there is with, you know, I mentioned the fact that we have a very broad portfolio with about 100 patent families covering the various inventions. There clearly is opportunity for that, an opportunity for out-licensing.

And maybe a last one.

No you guys show assuring a bunch of really interesting technologies.

Modular technology is coming up at <unk>.

Considering the current.

Laser focused on <unk> are you guys considering out licensing some of these technologies to other firms.

I think there is with I mab.

And the fact that we have a very broad portfolio with about 100 patent families covering the various inventions that.

But clearly the opportunity for that.

Christian Itin: You know, part of that is what you saw us do last year with the collaboration we put in place with Moderna, and there is additional opportunity. There's some smaller licenses we've granted as well over the years to aspects of technology.

That opportunity for out licensing.

That is what you saw.

Steve last year with.

Collaboration we've put in place with Madonna.

And there is additional opportunity there is some smaller licensees with grounded as well over the years to aspects of technology.

Christian Itin: So there is clearly opportunity for that outside of one of the portfolio that we're pushing on. All right, thank you for taking all of our questions. Thanks a lot, Bill. Appreciate it.

That is still an opportunity for that outside of the portfolio that we're pushing ourselves.

Alright, Thank you for taking all of our questions.

Thanks, a lot Gail appreciate it.

Operator: Your next question comes from the line of Asthika Goonewardene. [inaudible] Hi, thanks for taking my question. This is Bill on for Asthika.

Your next question comes from the line of Maury.

Your line is open.

Yes.

Hi, Thanks for taking my question. This is bill on for Africa.

Asthika Goonewardene: We were wondering if the MRD cohort, would that data be ready for the first half 23 update? And then also subsequently, we're just wondering in your hands and your experience, on average, how many multiple myeloma cells are double positive for CB19 and DCMA? Thanks. Thanks for joining, Gil.

We were wondering if the Mardi cohort would that data be ready for the first half 'twenty three updates and then also subsequently we're just wondering in your hands in your experience.

On average how many multiple myeloma cells, a double positive <unk> 19 in the CMA.

Thanks.

Yeah.

Thanks for joining Gill first question related to data, becoming available from the marquee cohort, whether that's going to be coinciding with the main data released from the morphological cohort.

Christian Itin: First question related to data becoming available from the MRT cohort, whether that's going to be coinciding with the main data released from the morphological cohort. That's something we need to look at. Obviously, we will have a range of follow-up on these patients, and one of the determinations we need to make is how much of a minimal follow-up we want to have in that patient group. But there may be possibility to include some of that data, at least on the initial experience in that group, from a safety and a basic activity perspective.

That's something we need to look at obviously, we won't have a range of follow up on these patients and one a determination whether you can make is how much of a minimum follow up to what I have in that patient group.

There may be possibilities to include some of that data at least on the initial experience.

In that group from a safety on the basic activity perspective, So we'll see we'll see how that progresses.

Christian Itin: So we'll see how that progresses. I think there's an opportunity, but in general, what you would like to have at the MRT cohort is a longer follow-up and actually see how these patients do over time, not only in terms of the initial response you can induce and the safety profile associated with that treatment. Thanks, and the CD19 and DCMA double positives, in the multiple myeloma population. Right, so the two aspects to that.

I think there is an opportunity but in general what you would love to have the marquee cohort is longer follow up and accuracy. How these patients do over time.

Not only in terms of the initial response you can induce the safety profile associated with that trade.

Thanks.

And.

The 2019 and the CMA double positive.

And the multiple myeloma population double pocket.

Alright, so sort of two to two aspects to that total bcm as the main the main target on that you would find on multiple myeloma cells.

Christian Itin: So BCMA is the main target that you would find on multiple myeloma cells. The interest from CD19 is sort of twofold. Number one, there is a what is believed to be a driving population of multivuloma that is CD19 positive.

The interest from CD 19 is sort of twofold number one.

There is a what.

Christian Itin: That's one aspect. So it's a smaller number of cells, but having a key role in driving the disease. And secondly, The fact that if you have your therapy and if you have an ongoing activation of your compartment using with the de novo generation of CD19 positive cells, not myeloma cells, but generally positive cells, that that probably is going to be helpful to actually sustain activity of the CAR-T cells over time as well.

What is believed to be a driving population of myeloma CVD.

<unk> positive that's one aspect so it's a smaller number of sales, but having a key role in driving the disease and secondly.

The fact that if you have your therapy and if you have it.

And ongoing activation of your compartment using.

With the.

The de Novo generation of CD 19 positive sales.

So Marcellus, but generally positive sales, but that probably is going to be helpful to actually sustained activity of the car T cells over time as well so they're likely two elements there that play into it.

Christian Itin: So there are likely two elements there that play into the rationale for choosing the pill. Thank you so much. Thank you, from the line of Ken. [inaudible] Hi, good morning. This is Dev on for Kelly Shi.

The rationale for choosing the targets.

Okay.

Thank you so much.

Thank you.

Your next question comes from the line of Kennedy Chief from Jefferies. Your line is open.

Yes.

Ken: There's a couple of questions for me. One is on futility analysis. Can you provide more color, whether it's safety or efficacy analysis, or how many patients per, for in-depth analysis, and second is the dual car. What kind of car do you think will be suitable to move the program into next step?

Hi, Good morning, this is Dave Kelly.

<unk>.

Just a couple of questions from me.

One is on futility analysis Kenny.

More color, but the ACO and efficacy.

How many patients.

<unk>.

But in that analysis and <unk>.

Dual card.

What kind of <unk> do you think.

We'll be able to move that program into next.

Makes sense. Thank you.

Christian Itin: Thank you. All right, thanks a lot, thanks, appreciate it. So the futility analysis, that was a predefined analysis point, obviously, for the study. And as you typically do in futility analysis, you look.

Alright, Thanks, a lot. Thanks I appreciate it so the futility analysis that was a predefined.

Analysis point, obviously for the study and as you typically do in futility analysis.

Christian Itin: The primary aspects of the program, one is the likelihood of the program to succeed. And that's basically a certain statistical power. You want to see that the program is going to succeed. And secondly, also, if you look at the overall adverse event profile, and you want to make sure that the profile of that product is as expected, and you do not pick up any undue adverse events in the program. So that was pre-specified.

Progress on the aspects of the program one is.

The likelihood of the program to succeed.

That's basically certain statistical power you want to see that the program is going to succeed and on the second half. Secondly, also obviously look at the overall adverse event profile. How do you want to make sure that the profile of that product is as expected.

You don't pick up any adverse events in the program. So that was pre specified and ultimately it is driven by the statistical analysis on your likelihood of success in the program as well.

Christian Itin: And ultimately, it's driven by the statistical analysis on the likelihood of success in the program. With regards to Auto-Onc 22, obviously the start of the Phase 1, as indicated in Kibraya ineligible patients, is obviously the initial data set that we're getting. Ultimately, this type of product, you would like to position at the same level of Kibraya.

With regards to Ottawa 22.

Also the start of the phase one as indicated in Cambrian electrically eligible patients.

Obviously.

The initial datasets over getting ultimately this type of product you would like to position.

At the same level of <unk>. So you don't actually want to ask sequential car T therapy that would not be a smart thing to do but actually have a product that has an ability.

Christian Itin: So you do not actually want to have sequential CAR T therapy. That would not be a smart thing to do, but actually it has a product that has an ability to overall improve the ultimately event-free as well as overall survival in that patient group by minimizing relapses due to antigen loss, and that's ultimately what we'd be looking at. When you look at the space... You see that eventually one year for pediatric patients is around 50%, so that's the number that you would like to actually look to improve and see improved in a product with a dual targeting approach in pediatrics. Got it.

To overall improve the ultimately the entry as well as the overall survival in that patient group.

I think relapses due to antigen loss and Thats ultimately what you'd be looking at when you look at the space.

See that about <unk>.

Event free survival at one year for pediatric patients is around 50%. So that's the number that you would actually look to improve and see improved.

Product.

With a dual targeting approach in pediatric patients.

Christian Itin: Thanks. And just to follow up on the, BCMA CD19 CAR, so what would be the bar for that product because of this changing treatment paradigm of multiple myeloma? You have to really postulate a very high bar for the program to proceed into the next steps of development. We do see a very good profile for the J&J program and we see good sustained activity on the BMS program. I think what you want to see is you want to see very deep molecular CRs that you can induce and you also would like to see an improved pattern with regards to persistence as well in the product.

Got it thanks, and just a follow up on the.

No.

<unk> 19 car so.

What would be the path.

Right.

Because of this changing the treatment paradigm for late stage myeloma.

But you have to you have to really postulate, a very high bar for the program to proceed into into the next steps of development.

We do see obviously very good.

A very good profile for.

The J&J program and we see good sustained activity on the BMS program.

I think what he would want to see if you want to see very deep molecular Crs that you can reduce and we also would like to see an improved pattern with regards to persistence as well in the profile I think those are two parameters that I think are give you can be picked up relatively early.

Christian Itin: I think those are two parameters that I think are give you, can be picked up relatively early or in the evaluation of the program. I think those are certainly two of the parameters we'd be tracking very carefully. Got it.

In the U.

Evaluation of the program.

I think those are certainly two of the parameters at least we'd be tracking very carefully.

Got it thank you.

Thank you.

Christian Itin: Thank you. Thank you. Your next question comes from the line of Simon Baker from Redburn, your line.

Your next question comes from the line of Simon Baker from Redburn. Your line is open.

Simon Baker: Thank you very much for taking my question. Three, if I may, generally of a more general nature, I just wonder if you could give us your latest observations on the normalisation of enrolment rates as we start, certainly in parts of the world, to emerge from the pandemic. Are we close to normal or is there still some distance to go? Secondly, on the Stevenage facility, you talked about the capacity of 2,000 batches per year. Is that from second half 2023 or is there a ramp up?

Thank you very much for taking my questions three if I may.

Generally if you will.

General nature.

I'm just wondering if you could give us your latest observations on the normalization of enrollment might just we stopped certain parts of the world emerge from the pandemic.

Are we close to normal.

Some distance to go.

Secondly on the Steve in each facility.

The capacity of 2000 batches per year.

From second half 2023 at least for the ramp up and could you give us.

Christian Itin: And could you give us some idea of the scope to expand? You talked about the option. I wonder if you could give us an idea of how much it could be expanded by. And then finally, a couple of weeks after your full year results, the FDA published their draft industry guidance document on CAR T development. I just wonder if you could give us your perspectives on that document and the direction the FDA is moving in now that you've had a good chance to review it. Thanks so much.

Somewhat.

Scope to expand you talked about the option when if you could give us an idea of how much it can be expanded by and then finally.

Sure a couple of weeks after your full year results. The FDA published that draft industry guidance document on currently development I'm just wondering if you could.

Give me give us your perspectives on that document and the direction of the FDA is moving and now that you've had a good chance to review it. Thanks so much.

Christian Itin: Well, thanks for joining, Simon. So the first question was related to the enrollment and frankly, the ability of clinical trial centers to support clinical trials. And as I think many of us have seen, there's obviously during the peak of the pandemic, many of the institutions were impacted heavily, not only by a lot of workload, but also as a consequence of losing a substantial amount of staff or a number of staff, particularly in those individuals who were active in the ICU entities. So that's been certainly a significant issue. We've seen a lot of that normalized.

Well thanks for joining our assignment. So the first question was related to.

<unk>.

Enrolment and frankly, the ability of clinical trial centers to support to support clinical trials click.

Clinical trials and as I think many of US have seen there is obviously a guarantee.

The pandemic many of the institutions impacted heavily.

Not only by a lot of workload, but also as a consequence of losing a substantial amount of staff for a number of staff.

Better.

<unk>.

Those individuals for axis.

Hugh.

As you.

Entities et cetera.

So that is considered to be a significant issue we seen a lot of that normalize theres still some geographic differences, but the vast majority of centers are back in our normal mode of operation certainly for patients that have the level of medical needs as we're seeing here.

Christian Itin: There's still some geographic differences, but the vast majority of centers are back in a normal mode of operation, certainly for patients that have the level of medical need as we're seeing here with OB cell in patients with acute leukemia that actually do have to get treated. You cannot wait to treat those patients. And we're seeing a normalization certainly for those patients. I think for some of the less life-threatening diseases that may still actually take a bit more time, but I think that's where we are.

Here with Ob sale in patients with acute leukemia that actually do have to get treated you cannot wait to treat those patients that we're seeing a normalization certainly for those patients I think for some of the less lifestyle diseases that may still actually take a bit more time, but I think thats, where we are a big chunk is actually.

Christian Itin: A big chunk is actually, or a big, big aspect is going to be the training of nurses and frankly, the hiring and training of nurses, which will take time. And it certainly will be a significant effort we see all across both the US as well as Europe and the UK. Second question was related to the capacity at Stevenage, the capacity at scale at the new facility will be 2,000 thatchers. We're obviously going to ramp up that capacity operationally as we're rolling out the product and as we're sort of growing the product.

Aspect is going to be the training.

Of nurses and the frankly, the hiring that <unk> posted hiring and training of nurses, which will be which will take time.

Certainly will be.

A significant effort with C all across.

With the U S as well as Europe and the UK.

Second question was related to the capacity of Stevenage.

The capacity at scale at the new facility will be two types of batches.

We're obviously going to ramp up that capacity operationally as we're rolling out the product and that's where we.

We're sort of growing the product doesn't make sense to actually have a full standing operation for that level of capacity and then not fully using debt so that needs to be an adapted approach as we go up the design of the facility set up of the facility supports about 2000 products a year the scope to expand actually would allow us.

Christian Itin: It doesn't make sense to actually have a full standing operation for that level of capacity and then not fully using that. So that needs to be an adapted approach as we go up. The design of the facility, set up of the facility supports about 2,000 products a year.

Christian Itin: The scope to expand actually would allow us to actually expand physically the facility and with that increase the capacity overall. And then the last question was related to the CAR-T guidance document, a document that was coming out from the agency. I think an important aspect is that obviously we're in a relatively new field still. There's a lot of learning going on, and I think having that type of learning and best practices sort of being started to be consolidated and sort of agreed upon, I think is very helpful. And so we're, you know, I think, you know, glad to see that we're seeing some of that guidance to be more formalized as it is outlined now in that direction. Great, thanks so much.

To actually expand physically.

<unk> facility in with that increase the capacity overall.

And then the last question was related to the car T guidance documents document that was coming out from the agency.

Think an important aspect is obviously, we're in a relatively new field steel.

There is a lot of learning going on and I think having that type of learning best practices are being starting to be consolidated.

And sort of agreed upon I think is very helpful.

So we're.

I think.

Glad to see that we're seeing some of that guidance to be more formalized as it is right now is that the next year.

Great. Thanks, so much.

Thank you.

Yeah.

Yes.

Yeah.

Operator: Thank you. Your next question comes from the line of Eric Joseph from J.P. Morgan. Oh, hi. Thanks. This is Sean. On for Eric Joseph.

Your next question comes from the line of Eric Joseph from Jpmorgan. Your line is open.

Okay.

Eric Joseph: So, sorry, my line was dropped for a little bit. I apologize if that's a repeat of the question. So, we are basically wondering of a follow-up question on the futility analysis. So, whether you can talk about, you know, some more details on the statistic assumption, you know, patient numbers comprising that analysis, and having passed it, is there a, you know, a minimum CR rate or duration of response that can be inferred from that? Thanks for joining, Sean. And yes, indeed, the question has been asked before.

Oh, hi, thanks.

This is Sean on for Eric Joseph.

Sorry, My line was on.

Dropped for a little bit.

Regarding the vessel I repeat a question. So we are basically wondering of a follow up question on those utility analysis. So what about you kind of talk about.

For more details on those therapies to consumption.

Patient numbers on pricing that analysis.

And having passed is there maybe CR rates, our duration will rebound, but can be FERC from that thanks.

Thanks for joining so all I meant.

Yes. Indeed, the question has been asked before so the futility analysis again, it's the statistical hypothesis, we obviously havent havent communicated what do you typically want to know is whether the study actually is in a position to reach the.

Christian Itin: So the futility analysis, again, it's the statistical hypothesis we obviously haven't communicated. What you typically want to know is whether the study actually is in a position to reach the design primary endpoint that you have set and the statistical outcome that you set for the overall study. And that is what you want to make sure that, indeed, the program can reach that outcome. And that's typically what you do in your futility analysis.

The design the design primary endpoint that he has set the statistical outcome that <unk> set for the overall study and that is what do you want to make sure that indeed, the program can reach that outcome and that's typically what you do in your fertility analysis.

From as indicated is primarily based on the clinical activity side.

Christian Itin: And as indicated, it's primarily based on the clinical activity side. And in our case, the primary endpoint being the complete remission rate, but then also, obviously, looking at the overall safety, which is also going to be taken into account as well. So those are kind of the key parameters.

And in our case the primary endpoint, beating.

The complete remission rate.

And then also obviously looking at the overall safety, which is also going to be taken into account as well. So those are kind of the key parameters, we haven't actually given more detail or more resolution on that obviously, we nicely past that point and are progressing well with the program.

Christian Itin: We haven't actually given more detail or more resolution on that. Obviously, we nicely passed that point, and we're progressing well with the program. All right, thank you. Thank you. There are no further questions at this time. I would now like to turn the conference back to Mr. Christian Eisele. All right, well, thank you very much all for joining today. Obviously, an exciting first quarter.

Alright, thank you.

Thank you.

There are no further questions at this time I would now like to turn the conference back to Mr. Chris can buy them.

Alright, well. Thank you very much all for joining today, obviously, an exciting first quarter and we're really looking forward to the second quarter with seven abstracts to be presented in the upcoming weeks and brokers, who will take the opportunity, particularly the EHR data to give you a more in depth update arrived the conference as well.

Christian Itin: We're really looking forward to the second quarter with seven abstracts to be presented in the upcoming weeks. And we also will take the opportunity, particularly around the EHA data, to give you a more in-depth update around the conference as well, and obviously put the data in context as well, outside of just a pure clinical data perspective. All right, with that, I'd like to thank you all for joining and wish you a great day, thank you.

I will say put the data in context as well outside of just the pure clinical data perspective, alright with that I'd like to thank you all for joining and wish you a great day. Thank you.

Christian Itin: Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all- [music] [inaudible] man, I'm a man, [inaudible] a man, I'm a man, I'm a man, [inaudible] I'm a man, I'm a man, I'm a man, I'm a man, [music] [inaudible] [music] Copyright © 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. [music]

Ladies and gentlemen. This concludes today's conference. Thank you for your participation and have a wonderful day you may all disconnect.

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