Q4 2020 Autolus Therapeutics PLC Earnings Call
Hello, ladies and gentlemen, and welcome to the Artless Therapeutics fourth quarter 2020 financial results Conference call.
As a reminder, this conference call is being recorded.
I would now like to turn the conference over to your host.
Boxer Lucinda Crabtree.
Vice President Investor Relations. Please go ahead.
Thank you good morning, or good afternoon, everyone and thank you for taking part in today's call on the financial results and operational highlights for the fourth quarter 2020.
And NUCYNTA Crabtree, Vice President of Investor Relations with me today on Delta Christian items, our chairman and Chief Executive Officer, and Andrew Oakley, Our Chief Financial Officer.
Before we begin I would like to remind you that during today's call I'll discussion will contain forward looking statements.
All statements other than statements of historical facts on this call are forward looking statements actual results may differ materially from those indicated by these forward looking statements as a result, and various important factors, including those discussed in the section titled Risk factors and our annual report on form 20-F filed with the Securities and Exchange Commission on March 20.
20, which can be accessed on the ethical and thank to pace at www, SEC Gov, and and subsequent filings we make with the SEC from time to time.
The forward looking statements on this cool and select the company sees as of today March for 2020, one regarding future event and should not be relied upon as representing the speakers' or the company's fees 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 companys views as of any date subsequent to today. Please be advised on today's call is being recorded and webcast.
On slide three you'll see the agenda for today and it is as follows Christian will provide a brief introduction and that will be followed by our operational highlights for the fourth quarter 2020.
Andrew will next discuss the company's financial results and then Christian will conclude without coming milestones and other concluding comments and of course, we will welcome your questions. Following our remarks.
So with that I'd like to and I'll turn the call over to Christian.
Thank you Lucinda and good morning to all of you and thank you for joining US I'm pleased to review our progress and for the fourth quarter 2020.
First on slide five I would like to provide an update on our programs. We have now entered into a more stable period post your initial COVID-19 peaks last year and our programs remain on track, we have not seen any further disruption and the fourth quarter last year.
We continue to work hard with our supply chain and logistics teams as well as our clinical centers to ensure timely continental and transatlantic deliveries of Luca for research and final products and samples for analysis and <unk>.
Order to support our clinical trials and ensure timely data availability and integrity.
We continue to monitor developments very carefully with a particular focus on patient safety.
And Q4, and indeed, the full year, we provided data updates from our phase one on old car study of oral one at ESA and June are also at Ash in December 2020, the pivotal program, Ottawa and one which we know can also referred to as the Felix study remains on track with data expected in 2022.
We also provided an update from the Alexander study of OTO, three and D. L. Bcl at IHA and ultra Ash last year.
And I will touch on order free a little later in addition, our academic partners published data from Phase a phase one study of <unk> six in the Journal Science Translational Medicine, and we're looking forward to moving out of six and you get to clinical development and.
In January this year, we provided a business outlook, where we guided on a renewed focus on the older. One program as part of this outlook, we announced our intention to partner our <unk> program <unk> III.
And finally in January and February 21, we strengthened our balance sheet with the sale of eight yes, it's under our ATM facility.
Net proceeds of approximately $15 million and also a public offering of Ats is raising approximately $108 million in net proceeds.
More detailed updates will follow on the next slides so moving into onto slide six.
We're focusing our Ottawa program on addressing the high unmet medical need and adult acute lymphoblastic leukemia, which is a truly underserved areas with limited treatment options and development.
The Phoenix study is designed to address the relapsed refractory population with data expected next year.
Building on the unique profile of Ottawa, and we're also exploring at Lilly and.
And relapsed refractory NHL indications and and primary CNS lymphoma. In addition to the next generation program OTO 122 is being explored in pediatric patients.
<unk> expects data updates for these programs and the fourth quarter of 2021.
Beyond data and B cell malignancies, we expect clinical data from all four and peripheral T cell lymphoma, and the fourth quarter and I'm moving our next generation programs forward into clinical development and collaboration with our academic partners moving to slide seven.
Focusing on our lead program and adult day L. L. I think it's important to understand that with this indication we have no approved car T therapy at this point and time, the only approved redirected T cell therapy explain sites, our earthly and a tube and map and in terms of other targeted therapies. There is also <unk> math of CD 22 targeting antibody.
Drug conjugate.
Frontline therapy is very attempts based on a very intense high dose chemotherapy regimens most patients do respond to that initial therapy. The challenge. However is that only 30% to 40% of the patients benefit long term, while the majority of those patients relapse. Once relapsed life expectancy is very short with a median so.
Bible of less than one year.
And the relapsed patients when they are fitted off will receive a high dose chemotherapy, followed by an allogeneic stem cell transplant with a small proportion of patients achieved and a long term benefit.
Patients not eligible for stem cell transplant or relapsing post transplant may receive additional chemotherapy blinatumomab or <unk> and map.
Ever known therapies drive long term benefit at that stage of the disease. This is a very challenging situation for patients and their treating physicians at this stage. These patients are typically and quite poor condition. Both from the immuno suppressive nature of their underlying disease and as a consequence of the off multiple courses of her.
High dose very toxic chemotherapy.
As a culture and spent a lot of these patients are highly prone to infection and a lot of them do die of sepsis.
As as the primary cause.
The core of relapsed refractory adult patients and the U S EU and Japan are approximately 3000 patients.
With high met unmet medical need and very limited new therapeutic options in development turning to slide number eight and we've put together a funnel to illustrate the treatment journey for patients diagnosed with adult females.
Unlike pediatric ALLL high relapse rates are common and it all day L. L. Despite favorable initial responses and therefore opening the door for a product like Ottawa and the significant unmet need and relapsed refractory adult day allows necessitates new innovation, which can offer improved durability safety and curative intent.
We will look to target those patients post receiving blayne on or in a tusa map, but also expect to capture some patients prior to having been exposed to the standard of care agents.
The initial indication and represents approximately 3000 patients and we expect data and the last line setting and will drive interest to move the program into earlier lines of therapy.
On the next slide number nine we summarize the key features of a successful car T cell therapy for adult day level.
The basic disease challenges involve very fast proliferating leukemic cells with almost stem cell like proliferative potential and patients who are in overall tour condition as a consequence of their underlying disease and also the toxicity of prior treatments.
So the product needs to combine very high levels of sustained anti leukemic activity with a good tolerability profile.
The technical solution for car T for the car T product on a one is it's highly specific but trans and engagement of the leukemic cells maximizing its activity and persistence, while minimizing cytokine release and neurotoxicity.
The result is a high molecular response rate and event free survival combined with a manageable safety profile.
Moving to slide 10, we would like to highlight some of the key data presented in December at Ash.
And the event free survival at six months was <unk> 69, and at 12 months, 52%.
Overall, we showed a median follow up of the patients of $16 nine months and first patients without receiving a second transplant past 24 months and sustained molecular complete remission with persisting car T cells.
This profile gives us a lot of hope that the program can drive long term remissions in a proportion of patients.
We're now conducting the Felix study to confirm these results.
On the next slide number 11, we're looking to put the auto one data and the perspective of the standard of care.
The primary treatment option for patients is playing a tube and Matt well introduce a map might typically be used as a bridging therapy.
If you look at the event free survival were approximately twice as active as clean a tumor map at six months and even at 12 months.
And where we are seeing a value of 52% event free survival for auto volume, we see a substantial.
And exceeding data compare to the six months value for the tumor math of just 31%.
When looking at the auto one data it is important to realize that 70% of the patients had either received privately and the tumor map or prior twos and app and failed on those therapies before entering the auto on trial.
Despite the elevated auto on activity compared to Atlanta tumor map cytokine release syndrome, and neurotoxicity are very comparable and a very simple way put with auto loans. We're looking at a program that has at least twice the level of clinical activity of line of tumor map, which is the current standard of care with a comparable safety profile.
We believe that the data is a very good foundation to move these products into a potential Registrational study.
Moving to slide 12, just another quick view on two of the key programs and products that are approved and the space, but form a camera, but from a commercial perspective, we're looking at Blaine side total and a two and map and the sponsor or Tuesday, Matt as you can see Blayne site has reached in 2020 annual sales of 379 million.
And typically patients receive an average of two cycles of the product, which translates to approximately 2100 patients treated with this commercial product globally.
Note that the majority of patients receiving the product are adults, we understand a key driver for sales accelerating into the fourth quarter, what's the expansion to community hospitals and segment and the U S. Beyond the initial academic transplant centers, which were where the product started its journey.
Wildly and site and a L. L. A is moving to non academic centers. We also expect the launch of frenzy and deal Bcl two established property experience in those centers, both developments bode well for our product with the properties of auto one.
Let's now turn to slide 13 first off obviously, the Ottawa programs at this point is in motion and the feeling it's page lumpy two pivotal study. It is a single arm study with approximately 100 patients with relapsed refractory disease.
The primary endpoint is overall complete response rate secondary endpoints include molecular responses as well as event free survival and duration of response.
And this program is ongoing and will recruit through the course of this year.
And as I've mentioned, we're also conducting some clinical additional studies to explore the activity of Ottawa.
ALLL population.
That includes indolent lymphomas and CLO.
As mentioned earlier, we're also exploring the activity and primary CNS lymphoma, which is typically neglected indication.
In December we also started and next generation version of the Ottawa program that looks at minimizing the relapse rate and pediatric ALLL driven by CD 19 antigen loss. The program is called Ottawa, and 22 and builds and Aldo on with its and unique properties and at a novel highly active CD 22 Comerica.
Antigen receptor.
Data presentation is planned for Q4 and 2021.
In summary, we believe there's a significant commercial opportunity to build an auto on franchise anchored in a L. L. Both adult and pediatric patients and also expanding into additional b cell non Hodgkin's lymphoma indications.
Turning to slide 14, moving.
Moving to our next program <unk>, three and diffuse large b cell lymphoma, we provided updates and oral presentations of the Alexander study at Astro Ehi, ESMO and Ash last year. The program as shown on a high level of clinical activity paired with a very favorable safety profile.
Two regimens of Penn Bleeds, and have protested and shown to be safe and building on what we believe is a best in class safety profile, we tested all of our <unk> III and outpatient setting and demonstrated feasibility.
Of the patients administered and the outpatient setting 38% were admitted with failure due to concerns of a potential infection and older discharged after the risk was cleared.
Patients were all at or well managed manageable without need for intensive care.
We're planning to partner the program considering the broad commercial footprint required to serve the outpatient setting.
So let us turn to slide 15 on.
For us our T cell lymphoma program currently active and the clinic and we expect to have a clinical update at the end of the year and expect a good understanding of the clinical profile profile of this product by then.
The sister program OTO five is prepared for an IND towards the end of 2020 volume the.
And the medical need and T cell lymphoma is high with very limited available treatment options for patients once they relapse after frontline therapy.
Moving to slide 16.
Always good to remind you all of the technology toolkit with developed at Artless, particularly as it relates to the suite of next generation programs. Some of which you will have you will recall, we showcased at ACR in 2020.
We're looking to move several programs into the clinic through 2021 and into 2022, including our first solid tumor programs, which we are very excited to be progressing.
Our cell programming and modules are designed to provide T cells with a high degree of specificity and activity on cancer cells, while strengthening the T cells Brazilians to withstand the hostile environment cancer cells create to fend off T cell attack.
Slide 17, you can see we have tabulated. These next gen probe, which alongside the expected phase one start dates as you will note and as discussed we started the pediatric allo and clinical trial of Ottawa and 22 in Q4 last year.
We haven't yet mentioned of course, Autistics and G, which expect to move into a study of <unk> positive solid tumors.
Particularly in Europe, plus stole my second half of this year on seven and prostate cancer is due to enter the clinic next year and finally auto eight we'll then move into the clinic in the first half of 'twenty, one and multiple myeloma old programs will initially be explored clinically and collaboration with Iraq and partners.
Now with that I would like to turn to slide 18 to tell you about a project we incubated with our research team and 2020. This program, we will look to actively partner and 2020 loans.
As we started to learn about the Sars cov two.
And Q1 last year, we got concerned about two areas that did not feature at the time and many of the discussions on the virus. The first was the risk of mutational drift, which was known for Corona viruses in general, but at the time not well established for Sars Cov, two and the second where the challenges this viral infection could pose for Ara patients with <unk>.
<unk> cell malignancies, and with multiple myeloma, who would likely only have limited ability to benefit from future vaccines. We.
We considered that vaccine approaches as well as antibody based therapeutic approaches may not work well for our patients and more generally could be outsmarted by the virus.
The approach we wanted to focus on should remain active even if the virus worked on Dakota, mutational uplift and could be used as a universal decoy against not only Sars cov, two and its variance, but equally against all Corona viruses using the same human receptors to infect cells.
What we've developed is an ace two FX fusion molecule, combining and enzymatically inactive form of the extracellular domain of phase two and a mutated constant domain from and <unk> to avoid unwanted immune activation.
This molecule can efficiently neutralize the virus by acting as a receptor decoy for the spike protein and Sars Cov two the FC domain has been introduced to confer and extended half life to the molecule and improved effectiveness of the product.
The product candidate has been tested in vitro and in vivo against Sars Cov two.
We have now demonstrated and in vitro models to efficacy of this product candidate against the U K B on seven and South Africa, and be well and 351 variance using lentivirus vectors suite of type two.
<unk> cost two spike protein and.
And Additionally, we also tested the ability of the product to neutralize soaps called one to further highlight the.
As you can see only the ace two FX neutral and Ics, all Sars cov two variance.
On brass therapeutic antibodies lose activity against Sars Cov, two variants and our inactive against Sars Cov, one, whereas obviously the product candidate is active against Sars Cov one.
We're very encouraged by this early data and the opportunity to develop a potentially universally neutralizing agent against Sars Cov two as indicated we're looking to partner the program for clinical development.
With that I will turn over the call for it to Andrew for our fourth quarter 2020 financial update Andrew.
Thanks, Christian and good morning, and good afternoon to everyone.
And if we move to slide 20, it's my pleasure to review our financial results for the fourth quarter.
Net to December 31, 2020.
So let's start with the cash position.
Cash and cash equivalents at December 31, and 2020 totaled $153 $3 million as compared to $210 $6 million at 31 December 2019.
And January this year and the company sold one 7 million ideas is under market sales agreement, resulting in net proceeds of $15 $3 million and in February of this year. The company conducted a public offering of $16 4 million.
And.
Clothing, the exercise in full by the underwriters of the option to purchase an additional $2 1 million and <unk> and offering price of $7 eight years, resulting in net proceeds of $108 1 million.
Net total operating expenses for the 12 months ending 31 December 2020, $168 $1 million Nathan Grant income and license revenues of $1 7 million and this compares to net operating expenses of $146 1 million.
Nature of the grant income of $2 9 million for the same period in 2019.
Research and development expenses increased to $134 $9 million for the year, ending 31 December 2020 from $105 $4 million for the year ending 30 <unk> December 2019.
Cash costs, which exclude depreciation and amortization as well as share based compensation increased to $116 9 million from $83 4 million, the increase and research and development cash costs of $33 $5 million consisted primarily of.
Firstly and increase of $8 $8 million and compensation and employment related.
Gross that's native lower travel costs.
And you don't increase in flow.
Head count to support the advancement of our product candidates in clinical development.
The lower travel costs, obviously due to the COVID-19 pandemic.
Lee and increase of $14 $4 million and project expenses as a consequence of the advancement of our clinical portfolio, which this includes research and process development and manufacturing activities and this has had reached repair and activate and monitor clinical trial programs.
And increase of $6 million in facilities costs and that relates to the commencement of the lease for additional manufacturing suite and.
And the continued scaling manufacturing operations fall asleep.
And increase of $4 million and it infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations efficiently and increases zero point $5 million.
And to professional fees and.
Lastly, and increase of $1 $7 million related to some logistics net.
This was all offset by a reduction in materials purchases.
Zero point $7 million and license fees and $1 1 million.
Non cash R&D costs decreased to $18 $1 million for the year, ending 31 December 2020 from $22 million.
And <unk> pushed on December 2019.
And $3 $9 million decrease is related to a decrease of $4 $8 million and share based compensation expense as a result of a lower fair value stock options and recognized in the period and Thats offset going on.
Zero point $9 million increase in depreciation charges.
General and administrative expenses decreased to 35.0 and $1 million for the year ending 31.
On December two 2020 from $39 $5 million for the year ending December 31, 2019 cash.
Cash costs, which exclude depreciation as well as share based compensation increased to $27 4 million from $26 $6 million.
There were increases of $1 $3 million alright, and.
D&O insurance costs, and intellectual property, and then $0 1 million and facility costs and this was offset by decreases.
$5 million and compensation and on the employment related costs, and 0.1 million and general office expenses.
Noncash G&A costs decreased to seven $6 million per day.
December 31, and 2020 from $112 $9 million for the corresponding period last year. The decrease of $5 $3 million is mainly also again attributed to lower share based compensation expenses as a result of lower fair value loans.
Share options recognized during the period.
Interest income decreased to zero and $5 million for the year ending December 31, 2020 from $2 $5 million from the from last year.
This decrease was due to lower cash balances held during the year and combined with lower interest rates for cash held on deposits.
Other income decreased to one $4 million for the December 31, and 2020 from $4 5 million.
And the prior year and that was primarily due to a weakening of the U S dollar exchange rate relative to pounds Sterling.
The decrease of $4 $6 million and the year ending December 31, and 2020 was offset by lease termination gains and one $5 million.
Income tax benefit increased to $24 $2 million for the year, ending December 31, and 2020 and that compares to $15 $2 million.
For the for the prior year and Thats due to additional U K research and development and tax credits receivable from H M. A C.
Research and development credits are obtained at a maximum rate of $33 three 5% without qualifying research and development expenses and the increase and the net credit was primarily attributable to an increase in eligible R&D expenses.
And the net loss attributable to ordinary shareholders was $142 $1 million for the 12 months ending Simba fluid you on and that compares to a loss of $123 $8 million for the same period in 2019.
The basic and diluted net loss per ordinary share for the 12 months ending December 31, 2020 was a loss of $2.76 per share and that compares to a basic and diluted net loss per ordinary share of $2 98 for the 12 months ending December 31 2019.
We can now update and our current cash on hand, which includes the recent financing financings in January and February of this year, we will extend their on the company's runway into the first half of 2020 three.
And with that I will now hand, the call back to Christian to give you a brief outlook unexpected milestones.
Christian.
Thanks, Andrew Let me conclude this to the management discussion with a review of the upcoming milestones and news flow through 2021, let's move to slide 22.
As we look at the year 2021, and there are a number of clinical milestones and opportunities for value creation, our chief and most imminent and operational focus will be continuing enrollment and dosing of patients and the pivotal phase and lumpy to Felix trial for auto loans in adult patients with relapsed refractory <unk>.
In addition, we have clinical activities are planning to initiate a clinical activities with older 122, or four auto fix and G. Auto eight during 2021 and are preparing OTO five and older seven for clinical trials as well and in conclusion on slide 23, I'd like to recap the major messages from today's.
Called the company the good kind of acquisition and combined with our cash on hand, we feel well poised for success, but very excited about the auto on program, we continue to enroll patients and.
And expect to report data in 2022.
We started the phase one program of OTO 122, and pediatric AML at the end of last year and expect first data to read out in Q4. This year. Additionally, we expect data at <unk> and <unk> from our old car study extension and indolent non hodgkins lymphoma.
We also are planning on expanding <unk> and primary CNS lymphoma with the car sales study planned to start imminently and.
As indicated and our business outlook and this year, we have announced a renewed focus on the auto on program, we're intending to partner our lead program <unk> three before progressing into the next stage of development.
Additionally, we expect phase one data from our <unk> four program our program for the and of peripheral T cell lymphoma. Later this year as well and expect multiple next generation development candidates to enter clinical development over the course of 2021 and into 2022.
Finally, with our successful recent raise we are in a position of strength with a cash runway into the first half of 2023, we're happy now to day take questions.
Thank you as a reminder, if you would like to ask a question over the phone simply press Star then the number one on your telephone keypad.
Again that would be star then the number one on your telephone keypad.
You have your first question from the line of Eric Joseph from JP Morgan. Please go ahead.
Good morning. This is Hannah on for Eric Thanks for taking the questions just a few from us.
Alright.
In terms of primary CNS lymphoma, how should we be thinking about the size of that market and given the limited clinical data and the indication and what about auto loans profile and gives you a company and its ability to show on meaningful clinical benefit.
And then I have a follow up after that.
Okay, well first of all thanks for joining appreciate it.
Peripheral CNS lymphoma is.
And a fairly tough disease, it's a disease that originates in the brain.
It's very similar pretty much a form of aggressive lymphoma.
And so there are a few things that you need to have with the product the product needs to obviously have good access to the brain and that is true.
For car T therapies, but also on else and particular, secondly, you need a high level of activity, which the program has demonstrated in the adult AML setting and at the same time, you would want to have a minimal amount of cytokine release.
Rockford actually generate which is one of the hallmarks of the program. So that the local concentrations could be cash flow I think those are the key features you'd be looking for in terms of the.
<unk>.
Profile for our product and we think <unk> has actually a fits this profile very well in terms of the size of the indication when we look at the debt.
The U S. We're looking at approximately 1400 patients.
And in that and that the relapsed refractory pack.
A portion of the disease.
So sizable not quite the size overall.
We've seen.
In adult day L L.
But not too far off from it either.
Okay, Great. Thank you and then also for auto and three what do you expect in terms of cadence of news flow from the Alexander trial, where and when might we expect additional updates on that candidate.
Right. So as I had indicated and the summary statements is that we obviously had four oral presentations of the program last year and the next presentation on the next data update we're planning to do it and the context of and actual publication of peer reviewed journal. So we have and ability to actually give a full.
A full overview of the data on rather than the 10 minute.
Short updates that we tend to give the conferences. The next update is planned to be actual publication.
Okay. That's helpful and if I could ask one more.
For the upcoming auto one update that you have and indolent lymphoma, coming and how can we expect safety and efficacy.
Parents about teen and adult allo and.
And to the extent that you can clarify that.
Well, we have given.
Obviously, the first four patients were indicated at the at the Ash update which is given.
And what are we basic reported on this that the patients all of all four received a metabolic complete remission.
And <unk> achieved that with a limited adverse events. It was a low grade cytokines and beliefs that was seen on.
But no no high grade cytokine release observed in these patients so that's sort of the initial experience.
And in General you would expect.
Safety profile that.
Would be less.
Actually more benign than what we're seeing and adult day and al just given the fact that the disease is not as easily accessible.
As a L L, a which resides and tomorrow and it's a place where.
Your T cells almost quantitatively.
Great too and all of a fit and lead to very high level of activity and a short period of time, which drives the adverse events, we're seeing and a L. L.
Obviously in lymphoma settings. The disease, obviously is much more distributed and <unk>.
Tends to be not as easily accessible and as a consequence, the adverse event profile.
Is is definitely.
Gonna be.
And quite reduced compared to what we're seeing and alo quite similar to what the experience is and has been.
And with some programs and the space.
Great very helpful and thanks, everyone for your question.
Thank you.
Thank you and your next question is from the line of Murra Goldstein from users and.
Please go ahead.
Great.
Yes, we can.
Excellent. Thank you.
Couple of questions.
First is on.
The auto side and.
And what program and the advancement of <unk> five and the bar you are expect alright expecting to your interest expense given that previously I think you said debt that no fight with only about after and evaluated what program and then I'm also just curious on auto III program understanding that yeah.
Granted to partner that program.
I'm curious as to what level of support it will acquire in the interim.
What you expect or hope you all will be with a partner you know going forward. If at all and then secondarily I just had a question on the ATM and whether that.
And that that financial product is complete at this point or are there still more opportunity to exercise.
Yes so.
But with the order for five question and I'll say order forest and dose escalation.
And we do expect to have a good understanding of the dose and activity relationship and order from order four by the end of the year.
Auto five it's actually worked up 2% and <unk> that will be planned for the towards the end of the year.
And so obviously it puts us in a good position and also building on the experience with order for two.
And to also think about the starting point in terms of dose for the.
For the explanation of all the five so in that sense, we're using or planning to use information from the order for.
Experience also to inform us.
For the conduct of the on Refis program as you remember this is the programs are only different and defense that they're basically seeing the same day very shapes element of the structure of the.
A T cell receptor beta chain, but it's an inversion with interest choose to isoforms and it's just an inversion of two amino acid. So you would expect that what we learn with auto for us.
He is highly likely also gonna be directly applicable to all the five.
And so that's the first question. The second question was related to.
Aldo three support required going forward.
And with the program.
At this point I think it's too early to speculate.
And I think.
That will be I think a conversation at the time point when we're ready to announce the path forward with the program on a potential partner.
On the.
The third question was related to ATM.
And most of his and place. This was the first time day ATM will be used.
And basically triggered by an inbound interest.
And and the facilities price.
Okay. Thank you.
Thanks Mara.
Thank you. Your next question comes from the line of angry Gavin how from campaign. Please go ahead.
Hi, good morning, and good afternoon, and thank you for taking the questions.
And I have a couple for me.
So you mentioned.
And if I missed that.
But I can assure you mentioning when exactly in 2000 and thank you and you are planning to start the trial and thin film.
On that.
Can you remind me of that please.
I think that's the word I was using was imminently.
So we're expecting that to actually start anytime now.
Okay, Great and if I may just give my follow ups.
You mentioned and as well did the readout for our trial was quite dependent on how the pandemic would affect enrollment and trial. So I was curious if you could share and just some thoughts on how that has been going so far and if you think there is actually the chance that you can meet that day too.
Timelines for data.
Are you.
You mentioned auto for the time.
You quoted was not probably not related to order for.
The order flow timeline, we expect to give us the data by the end of the year in terms of dose escalation.
Enrolment of OTO four is running well.
It's a study we're conducting predominantly in the U K and in Spain.
And we're actively enrolling and treating patients at this point.
Alright, thank you.
Thank you and.
Your next question is from net.
Phipps from William Blair.
Your line is open.
Hi, Thanks for taking my questions Christian and I actually I was wondering if I could ask a question about the <unk> program.
Couple of things and this based on the car construct the bottle one and.
And do you plan to look at.
<unk> or NHL and really my question being do you think and allo product can achieve the persistence and needed for a durable response and a L. L or it is better suited for something like NHL, where.
Data so far shows you may not need the level of persistence.
And for these sales to achieve durable responses.
Yes. So so first off we haven't guided actually on the Comstock were using and the Allo program.
We will we will make that public when the program is underway. So we haven't actually guided on that yet and we'll do that obviously when the when the study is up and running.
The second question is I think a very important one.
And I did highlight the sort of the sort of.
The success factors that we see for car T program and a L. L. I'm under the fundamental factors did you sort of have to get right is very long persistence, we're talking 18 months persistence and maybe longer to get into long term benefit.
That is an enormous challenge for any program on the autologous side and it is a daunting challenge for any allogeneic program, because you basically need to create and allogeneic product does not get recognized by the patient's immune system for that period of time.
We have no evidence in the space today that this is anywhere close to being feasible. So when I think about the disease settings a L. L.
The most challenging disease setting to get to long term remissions with and with the knowledge and April at program.
If you try to get sort of a bridge to transplant you may try to do that you might try to see whether that might give you some activity, but if you want to get actually sustained responses. This is probably going to be the hardest hurdles to take and.
And some of the lymphoma settings. It looks like based on the initial experience that we've seen with <unk> and DLP, so that the activity could be.
And sort of ex basically.
And successful.
Also from a durability perspective.
Even if the activity would be delivered for a shorter period of time. So there is probably more of a likelihood there and more of a chance with and allogeneic product to be active in certain non hodgkin's indications. However, the caveat. There is that this may be true for more for a more aggressive like the mobi C L.
Not.
Not an easy not an easy hurdle to take to be clear.
But it may likely he's a challenge when you look at any of the more indolent forms of non Hodgkin's lymphoma, where we have disease that basically with everything we do today.
And still real.
Drink of relapses after extended periods of time.
I would assume debt non hodgkin's indications on the inland side.
Will quite likely require significant levels of persistence.
And potentially the aggressive forms of non Hodgkin's lymphoma might create a bit of and opening with a shorter duration of persistence.
But whether the month or so and persistence. We're seeing to date is anywhere close to what is needed and I think remains to be seen.
Okay, Thanks, Christian and fraud afford and I touched a little bit on.
And kind of benchmarking empathy, but with the one patient that has been shown to date I mean they achieved.
Please and molecular response, but it wasn't durable.
Based on the disease and just everything you know do you think a lot of patients and this study will be pushed to transplant if they do achieve.
Deep response or is that it's allowed and the study.
I think it's difficult to tell at this point and time I think if you get patients into.
And to complete remissions and these are met.
Metabolic complete remissions that we typically score and these patients.
On that obviously is a good starting point, but you need to show durability of effect, obviously, what we have reported on both a whatsapp.
It was based on and extremely low level of the product just 25 million sales.
On asset, which is the entry dose and the dose escalation.
And well, obviously have to see where we get to ask for dose escalate.
And this is also what we're exploring at this point and time.
In terms of of transplant shock, but isn't ease and option.
And that at times is used and.
And tip.
Typically the patients that we're all dealing with here on patients that off and actually have already relapsed from a transplant.
And so.
Doing second transplants is tends to be a lot more tricky not too dissimilar from what you see on that.
In the NDA and all setting as well.
Alright, Thanks Christian.
Okay. Thanks, Matt.
Thank you.
Your next question is from the line of net Abbott from Wells Fargo.
Go ahead.
I think Christian.
And thanks for the update.
And just to clarify on.
Alright.
That's going to be starting that trial and gating.
On data from auto.
<unk> seen enough to commit to the IMD.
And I think with regards to the non clinical development you can do there is theirs.
I don't think there's anything more I think we can really learn about the program what we'd like to sort of understand from the <unk> program is where what range do we see the active level of the program. So that we could sort of fine tune and actually the entry level for the older. Five study I think that's probably the key parameter to come out.
Should we.
You can have.
Challenging safety event as an example, with old afford and that May all the staff and input impact on the program.
But bar that I think the primary information that we would derive from the order for studies actually understanding the and.
The likely entry point for the for a short and dose escalation for all the five.
Okay. Thanks, and then.
And what you've seen on.
And in the factory.
Operation.
And a way to go next and in.
Cash runway guidance did not allow for expansion.
Okay and mitigation program in total.
And you know presuming that you're also looking at commercializing the product within the cash runway as well.
So when we look at the at the current program. Obviously the focus is on that on the relapse refractory setting and we include we will have patients that will be.
Post relapsed post planar or posting and the tusa math as well as patients that are and have not yet been exposed to either one of the two agents. So it's going to be.
Yes.
<unk>, two slightly slight variations and the patient population.
And that's going to be and important obviously.
Aspects to sort of capture.
The entirety of the relapsed refractory part of the population.
We will also explore.
The patients and <unk> status as well within the study at this point this is not part of the.
Of the debt.
Pivotal part of the study, but we will obviously have to see as we go forward whether that might be common element.
To be considered.
As we think then further to the opportunities in adult day levels, clearly I think theres and interest, which we would expect to actually really get going and full steam with market approval of the product is to move the product into early line of therapy.
And there are several opportunities there that you can look at either into.
Ah patients high risk populations and the frontline setting or then.
Certain settings, and the second line setting as well so there's opportunity to grow the opportunity to grow the overall patient base.
Within AML and sort of create a broader footprint not too dissimilar from frankly, what you're seeing.
AMG and work on with Plains cycle working from the back and towards these stages.
On which I think gives you a pretty good sense of where you can go and and what you need to show.
So those are kind of probably the key aspect obviously, what we are doing and parallel it is that we're exploring the activity on the product and adjacent indications and I think what that gives us a good information to debt actually pick the indications to sort of add on and.
So to the extent that revenue stream.
Building from our core of a on the El Limon and further out part of that includes obviously the pediatric.
And that we're doing which is certainly one of the areas.
That we have to be active and no matter what given the indication.
And I think that is clearly and activity that we'll have a priority and then as we look into the other indications I think it's going to be driven by the data and the.
And in terms of the rollout and capacity we have.
Great. Thank you very much.
Thanks, Nick.
Thank you.
Do you have the next question from the line of Byron and then found Jefferies.
Your line is open.
Yeah, Hi, guys. Thanks for taking my questions.
On auto one for the indolent NHL data expected at <unk>.
Question, how should we be thinking about that data should we be looking at zuma five as context for that dataset.
And first of all thanks for joining.
First off I think it's a good data set because it it gives to defer and understanding of what the.
Look the car T can do and indolent lymphoma and particular in decades.
On a follicular and then it gives us obviously, a sort of a good benchmark to look at so it's certainly a good starting point I think when we look at the space I think there are two things that stand out and the indolent lymphomas.
And that is debt obviously similar to <unk> most of the patients are not treated and transplant centers, most patients and not treated and impacts should patient segments, either so I think what you need to find us through to the sweet spot of activity and a very good tolerability profile and so those are the two things we're looking at.
And so to get and initial understanding of what the profile of the product looked like in this and non hodgkins indication that indolent setting.
And.
Are you, allowing patients with prior city and 19 to come into that study.
Right now and actually be conduct that so this is a study where it's an extension of the of the old car study and actually adding additional arms to the study.
This study is conducted in the UK.
Sort of limited access for patients with indolent lymphoma, we're probably starting to have first patients getting access.
In Mcl.
But at this point and time there are no patients.
And that are sort of post.
Commercially available car T and this space and okay.
Got it and then on.
On the CLO cohort for auto and one question.
You know Theres been limited success, I guess with the CD and 19th and <unk> what gives you confidence.
And this cohort.
Oh C. L. L is interesting.
And as you pointed out because it was sort of.
And reasonably challenging indication I think to crack what we've seen and probably the best day that we've seen is the license sales data in the space looking at.
Treating patients in the presence or the absence of scrutiny and.
Potentially a slight improvement.
Improvement of activity with the improved and.
Basically in combination with Ibrutinib.
So so the fundamental challenge and sort of twofold. The first is the overall activity actually has been probably below what you would have expected to see and other.
Lymphomas and secondly, there has been quite significant levels of toxicity recorded still and these patients, but I think you have to sort of work on both ends of the spectrum and actually create then a sustained level of activity and these patients.
CLO is particularly challenging and defense that obviously, you would need to be able to also.
And also put pressure on.
On the leukemia off for an extended period of time, So I think persistence will be important but also the overall adverse event.
And I think will be critical to see that you can whether you can translate the initial effects into a long term benefit those are obviously two properties that we see the auto on program to certainly and ALLL demonstrate very nice level of activity, but also a good level of differentiation to other programs.
And and that's what we're why we're interested in and actually exploring.
On that particular indication and see whether and whether we can get an adequate profile there.
Great. Thanks for taking my questions.
Thank you Barry.
Thank you.
We don't have any further questions and define Sir please continue.
Alright, well. Thank you very much for joining I. Appreciate you taking the time today and we're looking forward to keeping you updated thank you and have a great day.
Okay.
Ladies and gentlemen. This concludes today's conference. Thank you for your participation.
Now all disconnect have a great day.
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Okay.
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