Q3 2019 Earnings Call
Greetings and welcome to select this Q3 earnings call.
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I'd now like to turn the conference over to your host Simon hardest Vice President strategy in Finance. Please go ahead.
Thank you brought and thank you everyone welcome to select a third quarter 2019, corporate update and financial results Conference call.
Joining me on the call today with prepared remarks, Andre Choulika, our chairman and Chief Executive Officer, and Eric Dutang, Our Chief Financial Officer.
Yesterday evening selected issued a press release reporting our financial results for the third quarter ended September Thirtyth 2019. This press release is available on our website at Electus Dot com.
Just as a reminder, we will make forward looking statements regarding financial outlook. In addition to regulatory and product development plan. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.
A description of these risks can be found in our most recent form 20-F on file with the FCC.
I would now like to turn the call over to Andre Andre. Please go ahead.
Thank you Simon good morning, thank everyone for joining us today on our third quarter financial incorporate update cool.
On our call today I would like to give you a brief update of the selected sponsored allergenic car T cell phase one clinical trials and the progress we have made over the past quarter and since the beginning of 2019.
The past quarter has been key far execution strategy into progression offer three leading proprietary allergenic car T cell assets.
Two phase one clinical trials.
Furthermore.
We are building out our clinical leadership team with the addition of Dr. Francisco as Steve <unk>.
Vice President clinical development following the acquisition of South cultural by Novartis, we strengthened our manufacturing capacity capacity with the addition of the CMO partner to replace tell for sure.
Now in addition to Mohammad why we remain on track with our construction of our in house manufacturing facility Smart an impact and we're thrilled turn out that first patient doping for melon easier one clinical trial for your car Tcs won our first wholly own allergenic car T cell product candidate.
Great and relapse refractory multiple myeloma.
Within three partner entry Standalone clinical development programs totaling six clinical programs ongoing and hematology.
Well, how far we have calm.
It's like this is persistent did pursuit to cure for Ken cures for cancer, and we intend to sustain this determination in the years to come.
Regarding our clinical trial annually zero on our first our new U.S. phase one dose escalation trial for you called 123 targeting relapsed refractory acute myeloid leukemia.
Well open soon for a woman I had the new manufacturer itself actually are to be release for the use of these in India clinical trials, we are paying clearance for the new R&D number in July for do it for this year after manufacturing the product under a refinery process.
This trial will be conducted I will can now MD Anderson, Lee Moffat and Dana Farber Cancer Institute.
Based on clinical data, so far with Apollo August car T cell therapy targeting CD 123, we strongly believe in CD 123, and the high value targeted for the treatment of AML and we're excited to bring this new treatment option forward without allergenic approach.
Bally's zero one.
Oh phase one dose escalation clinical trial for your car 22 targeting relapse refractory b cell acute lymphoblastic leukemia or BLM.
Opened for enrollment at will Cornell Medicine, and we'll open at MD Anderson and University of Chicago Cancer Center.
We're excited about the new treatment option for this product candidate brings to patients which include both patients that have relied full linked and prior cdnineteen directed car T cell treatment.
Finally, I'm very excited turned out that the first basin had recently being dosed in our Melanie zero, one phase one clinical trial for your car Ts one.
Targeting relapse refractory multiple myeloma I never car T cell targeting targeted in the space.
Yes, one also name Slam seven.
As a target because of its relevance in the treatment of multiple myeloma by allude to them out but more local antibody.
This trial officially commensurate MD Anderson cancer Center and is also open that tech and sign married and cancer Center.
We're looking forward to presenting interim data from these phase one dose escalation trial in 2020.
We have previously covered to design and intent of these studies.
But would like to remind you that.
These all our phase one dose escalation studies, where we look at the following main parameter.
First of all our first in human study our phase one dosing dose finding studies, we have learned from historic analysis and other autologous and allogeneic car T program that an early strong expansion of car T cell is an indicator for therapeutic performance, we believe that allergenic.
Our T cells are very capable T cells and they are derived from healthy donors, it's important to determine to write those before moving into the expansion and registration phase at the current stage, we're starting to where it's very low doses and try to find effective and maximum tolerated dose.
Second.
We are looking closely at the safety profile of our JV car T cell program, which include the familiar side effect of autonomous car T cell therapy, including Cytopenias cytokine release syndrome, and CNS chief of boxes city, as well as graft versus host disease or gvhd.
Which is unique in the allergenic car T cell therapies.
No signs of GBG over great to any of the select is sponsored license clinical trial has been seen so far this is an encouraging.
Fine and is an achievement for the manufacturing process established by off.
Third we are looking at an early early signs of anti tumor activity here, we would like to reiterate the initial dose start.
At level, which are below those levels approved for Tal. This car T cell therapy, such as Carter Kimbrough, NGL DSTL and Ll.
Following safety as the primary endpoint, we determined to anti tumor response at day 28 post Carty injection a second secondary endpoint in this phase one dose escalation trial.
This leads me to delight part of the Preconditioning and car T persistence, which has been a widely discussed topic of the allergenic car T cell approach.
The patient were seeing in our phase one study are usually heavily pre treated patient, including failed autologous car T cell therapy, presenting low T cell counts and considerable tumor burden.
Here are careful preconditioning regimen prior to car T cell infusion if necessary.
On one hand initial data of the response the good indicator for long term durable remission on the other half.
Long term car T cell persistence leads to longer term side effect in our phase one study, we would like to measure to sell expansion and persistent for few first week.
We following the initial building.
Coming to our partner program, our licensee survey in our gene has made progress with the filing of I, Indeed, an opening enrollment.
You car T 19 in non Hodgkin lymphoma also called our fiber one and new car TB Sammy multiple myeloma also called Aloe 715, as well as the driving.
The clinical progress for your car T 19 in Ll complementing our effort in covering to mange already have hematological malignancy and area large unmet medical need I.
I would like to say few words about our main manufacturing, which is a central and a key point for our future success.
We're currently building out our U.S. manufacturing site in Raleigh, North Carolina.
This is a 92 square foot facility.
Which is designed to ensure to stable supply of our latest generation of gene edited cgmp car T cell for both clinical and commercial sell doses and is expected to go live in 2021, we're very excited that as of November last year Bill monkeys has.
Joining us as our lead of head of manufacturing and coal Technical Corporation previously had manufacturing and background.
Bill has been building our team in rally, which is growing fast and will be fun mental in building blocks reflect the successes in the future, but it's also adding all of the technology, the technical operations, including Smart in Paris.
As a richer and manufacturing independence were expected to go live with an in house the fleet in Paris, and 2020, which is designed to manufacturers certain starring material for our car T cell Pro production, which is also expected to support to work off our contract manufacturing partners mold.
Matt and longer.
And on all fronts, we're investing in an exceptional talent in area of high impact one of these aereo.
Our focus is our clinical leadership team.
Faster Francisco is stable and TPG join our team as Vice President clinical development in October Dr., if Dave as a board certified medical oncologists was more than 20 years of experience.
In academic drug development Dr. its teva veteran in the oncology space was an exceptional experience and track record that include leadership roles in more than hundred clinical trials in an impressive number of peer review publication. He currently serves as junk professor of dermatology yet in Europe .
And why you school of Medicine.
We're excited to enter a disclaimer next clinical development phase with them together with our licensee Allergan uncertainty like this is extending its leadership position in the allergenic car T cell space with now pool of five different target in clinical development.
We continue to benefit from strong operational flexibility to achieve our clinical milestones given our strong cash position with that I would like to hand over to our CFO . Thank you Tom Inc. Please go ahead. Thank you on me.
I will provide a brief summary of the consolidate keeps final short of Cellectis.
Reminder, sitting here is a 69% to show and Kelly our publicly traded subsidiary.
You can get the breakdown of the consolidated fund on short prepare on the I've for between Silicon and Candy Yep.
Third quarter 2019 financial results press release.
I will act two on the present, the sixties financial performance since the case management at already presented that Q3 2019 earnings.
Festival I would like to 80 right that we focus our cash spending at Citi Keith on the footing objective.
They are looking at how deep pipeline of product candidates, including the manufacturing and keep retire a few kept went to three you kept 22 and you can see as well.
Reading out said, yeah manufacturing capabilities impact on smell.
And Anthony our manufacturing and sneaker departments, including hiring talented pass on that such as tight on Cisco as Taylor.
As of September 20, Nineteena sitting on a standalone basis without Kt has proved to be on 9 million that out in consolidated cash cash EQM, John financial assets and have a cash.
These cash position would be sufficient to fund seductive standard operation into 2022.
The net cash now which corresponds to net cash flow use by operating activities capital expenditure and needs that payment what 52 million data for the first nine months of 2019.
Rich $19 million is attributable to the third quarter of 29 Q.
Operating losses were 57 million that out for the first nine months of 29 team.
Roughly $16 million up is attributable to the tough quarter of 29 Tina.
R&D expenses increased by $3 million up to 53 million that out for the first nine months of 2019 compared it to 2018 and Asian expenses decreased by 7 million that up to 15 million that out for this mtell yet.
Revenues and other income decreased by 5 million to adopt to $17 million due to a decrease in recognition of upfront payment already received and R&D cost of investment. In addition to the same property collaborations.
This was partially offset by 5 million that out milestone revenue. In addition to I know site one.
Can you can develop man I think of naturally the third quarter of 29 Q.
Finally financial gains were $11 million off in the first nine months of 20. Thank you.
To conclude I would like to say if you work on the consolidated financials.
The consolidated cash cash equivalents current financial that said and of entity cash position, what three on 67 million data as of September Updip just 2019.
The consolidated net loss attributable to shallow depth of seductive what $65 million up all wondered on 52 cents per share in the first nine months of 29 team.
This represents an increase of 9 million no doubt about 2018, which was mostly explained by an increase in consolidated operations lessees.
The consolidated adjusted net loss attributable to shareholders upset aktiv, which exclude noncash stock based compensation expenses.
48 million that out all wondered out and 12 cents per share in the first nine months. It of 29000, an increase of $20 million up about 28.
I will note down the presentation back we're about to sign for closing remarks.
Thank you very much Eric and this concludes our prepared remarks, and we would now like to move over to QNX. Operator. Please go ahead.
At this time will be conducting a question answer session.
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One moment, please while we pull for questions.
The first question today is from Gena Wang of Barclays. Please go ahead.
Thank you for taking my question and just first question is regarding the you call 123, and a new D. fine.
Just wondering I mean that due to the production process change.
Can you give a little bit more color exactly what that is and what that apply to other programs.
[noise] [noise], Simon do on or I'm, sorry, yes.
Hey, Tina Thanks, so much my other question. So this is particularly for you part 123 Weve Remanufactured. This program throughout the winter of 2018 into 2019, and we've previously expressed that this new product and has been following a new manufacturing process and.
This new manufacturing process actually a yielded a product with higher potency specifications than we had previously yielded in the manufacturing and so that triggered a the FDIC asking for basically a new I in the filing to show more follow up data.
So that's what the background specifically for you card wanted Threem and we've now concluded those discussion and we're actually really really excited about the target and the product.
And we're entering this into clinical development now, but net net dissipated and new idea filing.
Yes, the definition offer product in the cell therapy stayed essentially to find more than 80% close my 85 might have defense budget process. If you change your process any change or process for your car 123 trying to build a better product. The first batches were manufacturing 2016 and for the second one locking in.
Second half 2018.
As we changed the manufacturing process, we've told that potentially we could break but like the product showed quite different from the initial product manufactured than DFT required us to filing windy file identified in July Jim.
Granted July and them coming forward.
Okay.
Oh.
Translate into the.
New though.
Initial dose.
No manufacturing process.
So interesting Lee.
Well Interestingly initially we started at the six month 25 to enter defense.
Which was the initial start dosed and when we had the whole from D.A.. We resumed the trial, whether those that was 10 times lower which is.
Six point 2005 tend to do fourth.
And then we're re escalated up to 2.5 tend to the fifth.
And currently we were able to convince DSD to bridge the initial.
Those that we stopped with with the former prologue.
And the new product exactly the same those which is 2.5 tend to defend so now start dose with this trial is 2.5 tend to the fifth with Kip give us a continuation on the initial escalation degree are doing.
So we're not going back at the lower dose.
Mhm, even with the higher you with this new manufacturing process and allow you to go back to 2.5 side, that's any as an issue.
Yes.
Okay, and then you know with this new manufacturing process is that.
You apply that new manufacturing process also to does she has won 22 the other programs as well.
Well every car in every target.
Has its own constrain.
Sometimes the target is slightly expressed on the t. cell and can induce for example.
Small expansion sometime to sell lagged the expression of the target slightly on the the T cells can induce fratricide, killing during expansion sometimes not so every car has a different type of process, but there are certain rule that you can keep from one manufacturing to another.
And a 22 is under the former has being manufactured under the former process.
Yes, one is an evolution of the formal process, but requires for example, certain anything that would allow to suppress the fratricide, killing and 123 is has been dunlop essentially due to certain conditions really particular to 123, where.
We now have a process that maintains very much to potency of the sell pristine from up to Dan.
Oh, it's the learning lesson from like.
From manufacturing to manufacturing and what we're doing we're trying to summarize this to work on the people versions that we're preparing to afford the the pivotal trial.
Okay. Thank you and my last question is more like since it's a question just wondering you know what criteria.
What would be the criteria for you to determine if certain goals. So expansion is enough.
Oh.
It's it's a very it's it's a hard question and it's not on follow up question. Unfortunately, I'm not going to be able to answer. This question. Because there is lot off translational research is conducting rounded.
And it depends for example, if essentially peripheral blood.
Disease, Dan you can measure the expansion essentially peripheral blood. He fits for example, such as bailout can find in bone marrow. It's absolutely not the same case for example, and now where most of the glass there present in the bone marrow the patients or multiple mile.
Alone were the.
Not that much like.
Personal blast that you can find in there so the behavior of the car and when you look at whats going on for a colleague. This car T therapy for example for TX one on 123, and the time or for even for VCM eight the delay in the expansion or this when the crs or to peaking up deteriorate.
As happens, it's totally different between MLL and in multiple myeloma cells are not present at the same place.
So it's difficult to measure that.
At the end, it's more like the the tumor response that you would like to see an ultra certain finds a surrogate marker of expansion that you could see are measuring referred to as or other things like that but it's really an open question and we are putting a lot of energy on translational medicine to understand this I think.
Part of the know how did you build up with the car whale with lumping.
Thank you.
Thank you.
Your next question is from Christopher Murray of Nomura Instinet. Please go ahead.
Hi, good morning, Thanks for taking the question just a follow up on manufacturing questions earlier could you remind me for each of the three programs you now have running in the clinic Oh your manufacturing processes. The process is that you will be using through commercialization or do you expect to change the <unk>.
In between.
Then secondarily and perhaps.
More focused on the CD 22.
Ah, Yes, one program.
Well I guess, how you chose your your first lowest dose.
If you think that's going to be efficacious and then if dose expansion opportunities will allow you to put together data sets that may be suitable for registration. Thank you.
[noise].
This is a very good question and the size of that those four see us one.
Is higher than for 123, and 22 started on mill in South Africa.
And.
It's very difficult to know exactly because as I said the.
Tumor burden totally different it's closer to what we would consider as an effective those but still a gold those end there.
And what you're interested in is also try to find the MTD.
Around the these doses and you know itself.
Well, it's very difficult to translate from what you've seen and preclinical development and also.
In comparison with what's happened with what's happening with Apollo This car T trials, including cephalon trials to understand what is the proper those SDN with patients. So we hope of course to see some general response end, there, but would it lead to derive dose I don't think so.
Start, but at least time, we were believed that we would be able to see sorry certain find what is interesting also with your car Ts Swan is that CSR slime at seven is present on a number of different type of.
White blood cell, such as NK cells T cells, b cells macrophages et cetera. So there will be part of the effort of the T cells that would be not only focused on the tumor itself, but also focusing potential and immune system, which is a good thing because it could deepened lymphodepletion limits.
On one side, but with divert the effect of the T cells out from the tumor in so maybe that those should be higher idea.
Do you want I mean.
And Chris I understood.
To follow up on the manufacturing question I just wanted to mentioned that the way. We're manufacturing right. Now is so sophisticated undersea GMP requirements that we believe we have a very stable product and we placed utmost importance on the fact that the manufacturing of the south now has to be consistent too.
The clinical trials and then potentially into registration. So that's why we're doing all this work on manufacturing process development that we have basically a very stable products that yield the same specifications batch after bad from donor to donor and this is I would say an area, where we have made some of the most progress over the.
Last couple of years to really come to a uniform product in specifications from batch to batch from Dona to donor to make this a true off the shelf concept work and so I think we're really setting the bar very high there also in the in this phase of our peers.
But we're very proud of that achievement it'd be in such a good product.
Okay, Okay, how many version.
The BLE version of the product the process for BLE BLE version has to be at close to what you had during the expansion like the dose escalation to expansion.
However, certain things should be at like daily crude so there is a bit of.
Operator can you then I mean, I believe were left and right. Yes. His one it's still connected.
Would you like me to report to the next question.
Sure, we'll come back to that yet.
Your next question is from Michael Schmidt of Guggenheim. Please go ahead.
Hey, guys. Thanks for taking my questions I guess, Simon the math to tackle that but.
If you if you maybe could us could remind us of your that the preconditioning protocols for CS won and you quite a lot of 23, and maybe talk a little bit about.
How you think about I guess balance saying.
And I'll, just south and process, then and how how are you maybe talk about how you decided to use aside move us Allen to some of it.
Program.
Yes, that's a very important question then something that we're really focusing a lot of attention on is the lymphodepletion for these so.
The the in the Lymphodepletion with Cyclophosphamide and Fludarabine is pretty standard and were using we haven't disclosed exactly the doses you had because this has also been dialed in for each program separately, but it's along the lines what you would be for the autologous Carty.
And we believe the data we've seen so far a really shows a robust expansion of our car T cells in that environment.
We have invented and brought forward the concept with Alan to the map pre injection and concurrently 52 knocked out in our car T cell and so this is a concept that we think is a very efficient one to basically prolong the lymphodepletion and to also prolong the persistence of the car T cells at.
It really depends on.
The program, how long, we actually one car T cell persistence. So we will update the details of the Lymphodepletion regimen as we're reporting the first set of clinical data, which we're very excited about but we think we have a very differentiated approach to the lymphodepletion, meaning some programs will have alimta is a map some programs.
Well not half Allen to them out and in some cases, we reserve the option to add onto the map later on so it's something that we really differentiating between the patient populations that we're seeing and we see that I wouldn't is a map can have a very long lasting effect on the reconstitution of the immune system of the patients were seeing.
Given that these patients are heavily pretreated its maybe not always the most ideal strategy to go for element to the map and at the same time, we are very encouraged with the early expansion and persistent generic or do you sense. We've seen just after cycle of fluid at Preconditioning, but without Allen season that preconditioning.
So it's something that we're exploring.
And we strongly believe as necessary it's differentiated approach.
Finally.
Our back, but one thing I would like to add to it depends also from the indication BLM at a different than AML is different than multiple myeloma. So each time, we have to assess this but the enablement fusing onto isn't our goal is here.
I guess, how much optimization as they're still unnecessary base based on what do you see and or how likely into that you get it right I guess the first try in terms of the exact protocols that are being used.
Well, so far we potentially think that women might not need some optimization.
You know you have to go through to dose escalation to end sand is but we think that our protocol that we have currently is a good protocol. It depends if we definitely see a problem, where we need to optimize et cetera. During the potential to optimize this but we think we starting here with Unoptimized Procol and we definitely think that this could go up to the expansion.
And then.
And we hope so.
Okay and then just.
Maybe regarding the Ameli trial, you know as we understand that AML patients, maybe a little bit more frail. For example, then monitor myeloma patients just given the prior.
Piece.
Maybe talk a little earlier patient selection process for the you acquired 123 study and sort of what are you doing it to minimize potential safety risks and that study, particularly.
While the patient selection is of course.
One of the main thing we've been working on in term of Flak age having like young patients the goal certain age and avoid for example, the fact of having to poor quality patients also not too heavily pretreated.
Before if something is really important no previous all the type of carcinoma cancer that they have the weight of the patients also important.
And.
Also the expression of the target.
This or face of the cell and so all these selection criteria are quite consistent from electronic trial Valley Annaly and Melanie general ones have like a very similar selection process, which might be can elect constrain at the beginning but would help us to add more consistent set of data.
At the end to determine the dose with a high consistency from like cohort two cohort while moving off the doses. If you have to lacks type of.
Of of criteria, then you'll lose sharpness and the data data gathered IDN and cleaning up the data would potentially have very a potential to develop this direct for coal for expansion and the people.
Okay, and then maybe one last sort of a bigger picture question, there's obviously a lot of.
Excitement neuron Bcm, a index is going to be a fair amount of data.
Thats at the upcoming Ascot friends are on became a targeted car T cell therapies, and just philosophically I guess.
What are some will leave the key advantages of CS won and how do you see see as one.
UK, one fit into the Matson myeloma landscaping context off a lot of.
Programs going after these may.
Well first of all we'd like Bcm may because it's one of the select this partner program like your car Bcm has been developed by select us a debate.
Pfizer and then became algae.
Under the name Al 715, and we definitely length is targeted.
Two telling to and from saying is that there is a lot of positive trials that are coming out from.
Other like either investigative sponsored we're Comping sponsored trial is bcm may and all the patient with screening currently our relaxing from BDNA. The fact, SAGD IBCM Mays also see.
Quite heavily secreted protein in the blood quenches activity, the Cds, which is less or not the case with Swan anti telling the truth actually when you look at CES, one and that's why thing that they'll have to the lab is.
Is a good proof of concept dairy like you don't have think proof of concept within multiple antibody for VCM eight if you multiply antibody that had been developer bcm may or by specific.
Cetera don't give you similar data as multi body weight Elotuzumab, where you have a 5% complete response and 35% partial response look at my team look at 22 et cetera older cars that have been the block is being developed to try to find a level of expression that would be low.
Fair enough.
That's high enough to make a car work, but never worked with a multi antibody gather perfectly comfortable multibillion I think it's a good final potential performance of the product idea. That's why we're encouraging we're excited about sets one as a target, but we definitely like also be Sammy as its of what our partners.
Alright, alright, thank you congrats on the progress.
Thank you.
Your next question is from Salveen Richter of Goldman Sachs. Please go ahead.
Hi, Thank you for taking my questions as Ross on for Salveen.
As you think about the.
Recent.
CD 123, Carty that was terminated on the clinical trials that are out about Nanjing legend is there any read through from that study.
Which has the same target as.
You cart 123 in terms of safety and adverse events.
Well.
CD 123 is there Dart trial for example, as CFO for some targets Cdtwenty three.
Car T and you have luck very interesting data there are produced there and like so like strongly invite you to check the data that can be produced so far hopeful licensed by I think Mustang bio, but for the legend it depends on how the car build for targeted therapy, if the cost per se.
Then you have a problem.
Because you want to three is expressed on military janitors.
If you keep the pressure where the continent, followed this basis with the car persist with pressure over the military janitors.
Then you won't be able to rebuild blood, even red blood cells come from nearly progenitor.
Sales et cetera, so it could be extremely toxic it's not like cdnineteen weren't can keep the car floating in the slot for eight years. The patient will end up with Cytopenias is fine.
Lymphoseek in a fair enough tied to deal with clinical Kenai fine because it can supplement with more global into patients in the case office CD 123 that targeted leads to Cytopenias and also with an ability to bleed through to build red blood cells. So it might be a reason.
Why.
That came up to this point, which is not the case of.
Thank you a pole and that's why I also would like very much the allergenic approach because at the hip and one procedure, where you can clean up only CD 123, Ultra you want to three presenting cells and then led the bone marrow because it doesn't hit at the.
I came at the point extend cells than they might make sense I was rebuild blood. Afterwards, if you maintained the pressure than you have a problem.
Very helpful. Thank you.
The next question is from Amanda Murphy of BT RG. Please go ahead.
Hi, good morning.
I just had a question on.
Presented data.
On a number of different next generation.
Type at it.
Yeah across multiple different indications I'm just wondering.
You might start to see that.
The product or.
The clinic.
I'm not trying to like I Didnt hear while the question can you repeat your question sorry on the bench.
I have dropped something in there.
Yeah, and live I, when I was saying that you at various conferences you presented data just around.
The edits that you're pursuing seven in the next gen.
Right, so thinking about your PD, one knock out things like that.
Yes, probably presented more data and then other out it was on that front I just was curious when they start to see if that does and that sort of pipeline if you Rob.
Well currently Toprol other developing CB 123, yes, one and 123 don't have for example can you want to knock out the next generation car and we think the card. If we were having the pipeline to treat solid tumors definitely make a difference with PD one knockout not only this.
But there is more sophistication.
Over the technology, we're having we have potential.
Options to for example use PD one adds let Pat for other type of chain and using this.
I guess, probably in the in the coming here will present, either us or partnered certain.
Evolution on the use our originated think technology to for example, such as the use of PD, one and an approach for solid tumors either buy in house projects or external Protex also so it's something we've been working for a long period of time and now I think its reaching maturity, it's probably not in 2020, there are going to.
Final 90 on our side because I think they have lot of cars on our plate.
Potential partner, Thanks could go for 90 points.
[noise] I know there in terms of the partner products.
I'm not sure how much you can describe but is there.
Efforts to partner there next gen.
Yeah, It's your talent out now or.
Just curious how much interest there Ben from partnership and licensing Thats when you already.
No it's like sooner because we're trying to do this in a non compete competing way was what select this is developing so.
We're not going to develop the disclosure of our partners and potential partners actually and.
That's why we think that.
It could be sooner than later.
Okay got it thanks very much.
The next question is.
Hartaj Singh of Oppenheimer. Please go ahead.
Great. Thank you for the questions I just got a couple.
One is just on you caught Monte pre Andre.
You know with starting a new R&D or other steps in terms of just the RV approval at various sites.
Could those be.
You know happen quicker and then the I think is what is the what's the time between.
Dosing cohorts I.
I know we've had very little of two weeks in as much as about a month and I'll hop where are you at that now with what you caught one to three and then I'll just follow up on Seattle.
So always between the first patient second at each cohort, it's like for four weeks, So 20 days.
In total between the first and the second dose for CS long weekend include two patients for the second dose.
And try to close the court as soon as possible.
And so in parallel with you can immediately these two basin depend for one to three it's like every 14 days afterwards and for 22 I think it's like every 20 days. So every trial is different.
And we will probably.
While we're walking through these trials trying to amend the trials to try to line up older trucks together, but we would like to be very cautious at the first dose of every cohort in keeping these 28 days to be sure that to take the direct side.
Yeah that makes a lot sense I got some alright I was just in terms of your question on the eye or be it though we have been very fast and progressing through the IB approvals and getting our hospitals basically to sign off on the clinical trials and the protocols following the new I Andy.
That was a very good question by the way because sometimes people forget that after getting an eye and be approval you have to work through the IR be is you have to work through budget with hospitals.
But given that we have such longstanding partners. They are those discussions when really fast and on top of that specifically in and now that centers were working with really are saying to us that there is such a huge unmet need for the relapse refractory AML patient population that they are just waiting for these studies to get initiate.
It it and we get on a daily basis requests for potential compassionate use for the product and even other centers with some very well known doctors want to initially its study.
This product so the pull from the clinic and what they're seeing for the patients need it's really there for this product and that's also why we're very excited to get this the on track.
Yep.
That makes sense Simon Onrad, I mean, I think that by similar companies had experienced some problems with manufacturing drinks right versus the branded products for example.
Next intercept and that was actually a big meeting with the FDA a few years ago. So the fact that you're seeing a kind of a manufacturing drift also to me is not or the ordinary I mean, this what biologics, it's not optimal but this will happen to biologics just would see US one you know.
The the question how does what what kinda patients you think you'll be treating Andre will these be second third fourth fifth line patients. When you include or exclude Elotuzumab failure is just any thoughts I mean it.
Multiple myeloma had has lots of different dosing regimen. So you got any thoughts on on where you'll be kind of trying to slot in at this early stage. Thank you.
[laughter].
Well.
Theres very light you as always is a very good question Heartaches here. The currently the patient were saying for multiple myeloma are heavily pretreated is like patient that have over 10 lines of treatment before.
As most of the time of course failed telogis cylinder relapse. After August treatment most of the time its bcm may.
And.
And the objective that from tried to show here is trying to move up the line, we prefer to avoid having people treated with elotuzumab because the half life of the paid the drug and you've locked at target at the end.
Yes.
Dara is way more you then elo tourism evidence of the Daratumumab and.
The good thing that has sat saying is that most of the multiple myeloma patients are treated for a long period of time and always fail. The targets. Yes. One is preserved off to the end, it's a very stable, Ohio Express target in multiple myeloma patients. So thats why we think that we can move up the line, where our proven the safety of the patient.
Product and we hope would the ease of use of these type of product and also the performance potentially that IDN would be able to do to move up interestingly also with a strong believers in combo, who.
Combo studies, and we think that are Caramels, our technology could potentially will lead us to make combo studies as all the type of drugs that are used in multiple myeloma that could enhance.
The activity of the car and like Sky rocketed chances of recover for depiction again.
Great. Thanks, sorry, one last specific question is that just remind us for you Ctwenty tree see us want to 22, how many patients will be in the first cohort and then how many patients. The next door to 3.3, I think you're mentioning that one or 210 to two if you could just kind of give us. A quick reminder, then again. Thank you for all the questions.
Okay Tony.
Hi, Thanks to your question.
We have to possibility to include between Pete to and five patients in each dose cohort and we have a little bit of flexibility here, because obviously, we want to go through a dose escalation quickly to come to the optimal dose as fast as we can but also a safely as we can so if we see and sub optimal cell expansion.
We would move quicker after a few patients to the next dose cohorts and if we see a very good response, we can extend up to five patients. So.
The we sometimes give like the overall number of patients, let's say up to 18 patients.
In a phase one dose escalation study, but that does not mean that we're running five patients on the sub optimal dose. So that's why it's a little hard for us to give the exact guidance, but we will definitely keep the street updated and I'll keep you updated in terms of how quickly we are progressing through this dose escalation we.
We believe although that now we're at doses with 2.5 tend to the fifth.
Per kilogram for you heard one to three going to six point 25 send to the fit for example that were just ahead of the optimal dose and we're excited to get there for you guys see US one we're starting at one times tend to the six cents per kilogram, which is the highest starting dose we ever had and any of our trials. So very excited to look at the entity.
Tumor in fact in that cohort as well and then for UCAR 22 were starting at the same dose one times enter the fifth as you heard 19, originally started and just as a reminder, at that starting dose already and we've seen some very impressive complete remission rates. So we're excited to see the next couple of patients in.
Each of those trials and we'll keep you updated on how large the cohorts will be.
Great Great. Thank you Simon Thank you Andrew Thanks, all that all the questions. Thanks.
The next question please.
For sort of William Blair. Please go ahead.
Thanks for taking my question.
A question about the reducing protocol in the studies.
Just wanted to your thoughts on our next week dosing and and at what point do you kind of trigger that with the protocol design.
And then you know a lot has been made about.
CD a positive alibey activity just wanted to get your thoughts there and just last question sounds like earlier in your remarks and talked about you're already seeing sub.
Allo or sorry, I apologize relapsed patients.
And in their trial enrollment do you think that you're cohorts for C. S. One and 22 studies will have a majority of previously treated autologous patients. Thanks.
Yes.
Yes, we do see love previously treated patients through the simple reason that there are lot of like you don't multiple myeloma BLS and.
And.
I do have flexi deferred like Cdnineteen car, you for 22 and for multiple myeloma, beating it stopped the case for ammo because ammo. There are no car typically is only part of lumped in this indication I think so we're seeing no pretreated patients.
The strategy of free Dozing is for me very important.
We are convinced.
And in the company.
This type of therapy could be developed into different weighed into single those that was the initial wave has been done for targets for the car was supposed to pursue the rest of the lack of the patient.
And we're.
You still have to go through the dose escalation to determine write those the twins to determine determination to drive those has been identified Dan we plan to go for more sophisticated way of injecting this.
For example to give one does at the zero second one at the 14 and then two other doses at 28 and potentially like one months later or do also combo studies was like different type of cars or potentially different type of molecules that could be combined with it which we could be gold.
From like Imids too.
Other type of Chemotherapies that can be given combination and that would require certainly certain.
The number off like a repeated injection. So we do believe in that.
Now.
It depends both of the state of what the patient has received before of course.
And maybe Roger to add to that that the Simon.
I think this is a very important question that you're bringing up with read dosing as we're also looking further into the future and into the bridge into solid tumor treatment I think with the off the shelf allogeneic gene edited car T cell approach, we really open the door to completely new horizon of treatment strategies and were able to read.
Those patients we have successfully shown that an hour and allow trial and we are looking forward to showing that potentially in other trials as well and you will see a lot of.
Publications and updates on the R&D site come up where we're actually working on very sophisticated gene and it's in our car T cell that enable either re dosing or a combination therapy with other biologics or chemotherapy is and then also specific targeting and.
Toxicities release against tumor cells. So we're really entering kind of this era of engineered cell therapy with our platform of gene editing and we're just blown away by the possibilities we have.
Great. Thanks.
The next question is from Augie Lee of Ladenburg Thalmann. Please go ahead.
Hi, Thanks, taking my questions most of the already answered about I Wonder I was goodbye.
Yes, the one.
It's a very interesting targets and.
And it's expressing motorboat different type of Santos and to use study as.
Well I mean sounds like you look right right high dose. So I just wonder do you have extra measures for safety precaution.
Sorry.
We don't consider it's a high those actually lowered those Dan.
Normally it's like the floor dose for relaxing car like a car activity, which is a non customer keurig.
So we do monitor with a very lot of precautions all the environment around the car T term off like neural talk.
The activity onto you might do boutique stem cells. So the barmer stem cells is something thats really important for CF one also.
It also everything concerning the gvhd and to distribution of the cells into patient and of course like the extension.
Of these cells.
We don't consider the goes were injecting is a quick and we definitely have all the level of injections. It's likely we go go through.
We have to keep in mind I would say that previously, but I think it's in real important point part of the activity of the car, we'll be focusing on other type of immune cells most of the.
Tumor on target cells are immune nude celso improve probably divert part of the product to deepen the lymphodepletion and Thats why we think that.
Those has to be higher also.
So yes, there are lot of different safety monitoring around this but we called damn thing that this current going to be Harman from.
Got it helpful. And then also question about you kind of minus three you mentioned the four M.A. out because that target expression on the stem cells and went to the quarter to policies too long to call the Mana toxicity.
But do you have any color on what do you think that the optimum persistent would it be forward to balance the plus the.
Efficacy and safety.
Normally.
When you look at literature.
The Matt the persistence itself has to be around like two weeks.
So thats the window word to self would act. After this what is the main parameter of functioning as the expansion.
If they expansion is high and very strong Daniel has a deep activity and Dan.
Yeah, it's totally different than.
The persistent itself so what we're targeting our as im pleased to have to sell persisted during the like a 20 days I really liked eight.
Period.
But.
What has to be monitored essentially the deepness of the the response and then.
Got it thanks, a lot of for taking my question.
The next question is from Sumit Roy of Jones trading. Please go ahead.
Hello, everyone. Thank you for taking the question.
It might be but if there's a good question but.
The U. court or want to see for the email do we know when the first patient is gonna be dosed and.
So what I could understand this from the dose given the time difference between dose level, one and two would be.
20 days apart and maybe from two to three would be 14 days apart, but within the dose level cohort one are they.
When do you did the part or how frequently are the enrolled.
Well one of them to any any color on that and the second question is.
If you can give us any color on.
Change in the quarter characteristic between the previous manufacturing and does that led to a new.
Andy.
I'm going to want to take this question, yes. So in terms of the first patient dose for one to create the should be imminently like we have as we said earlier, we have really gone through a lot of paperwork here, we've done our homework, we remanufactured, we filed a new I, Andy we went through the hospice.
<unk> approval, we're working with some of the best hospitals in the space you know.
While karnow MD Anderson, you know the University of Chicago like these are all really amazing centers that were very happy to work with so we think that the first patient dosing should be very soon and then we will hopefully give you updates on an ongoing basis.
Well, we are with enrollment, but we're very excited for this to kick off.
And though the gap between the patients in this first dose cohort are seeking to school how frequent is that going to be just to get a sense. When we should should we expect early data in mid 20 already that really going to be.
End of 2020 just to get it so.
Yeah.
The enrollment timeline. This four weeks between the first two patients on each dose cohort and then two weeks between each patient on subsequent patients in the same dose cohorts. So that gives you a little bit of a timeline idea.
How fast we can enroll patients. We also want to be very careful with the patient selection. Just in these first few patients because we do unfortunately C patients that have gone through multiple lines of treatment relapse refractory AML. As you know is a very very difficult to treat disease and so we want to be very careful with.
Oh patient selection as well.
And again, we have.
Some of the best sensors with a lot of a selection of patients for these trials, but the timelines are as we said.
Four weeks between the first two patients and then two week thereafter.
And any color on the well.
What we change between the product characteristic between prime manufacturing and this because you know with new.
More potent product come so.
Bush event worries come in if it's going to be.
Triggering more at levels.
So I think one important aspect is that we have really perfect. It be reproducibility off the product. So our let's say average power and expansion potential of the product is higher but also it gives us more confidence and or centers in patients more confidence that they're getting the.
Optimal product so I think that's of utmost importance and the higher potency of the product that we measured in our preclinical testing for this product it's difficult to say how this is directly going to translate into clinical development and we believe the doses that were injecting into patients are still way.
Below the currently approved autologous car T cell dose is just as a reference point of course these are different diseases, but we think that we're at a good dose expansion place currently and where we're at a good.
Dose in general and the new product. It just gives us more confidence that we're moving forward with the best possible product.
Thank you I'm just one last it maybe a little broader question.
As we know in the allogeneic set up you, there's two leading match well get the most.
And that.
Essentially would limit.
The persistence of these cells, and which is perfect, Florida emo kind of set up what do you don't want you sense to persist very long, but didn't kicks off multiple myeloma other ones. How do you think that a limiting factor for the alleged allergan ache approach versus not positive approach.
No. We don't think so for December reason that.
The big power often allergenic approach is the ability to read those.
Several times the product.
We don't seriously I don't see any advantage over an autologous approach because he very cdnineteen like all b cell linked.
And then persistence of the car is fine.
Because you can live with or without B cells.
For a lot of other targets such as for examples here for you definitely don't plan to target like the car to stay there forever. So you see a lot of cars such as for example be Sammy card for a targeted therapies that are used currently they don't pursue it.
Over.
It's better to be able to develop a protocol was repeat dosing or like a real structure.
With monitoring for example, the tumor burden and you can repeat those deflation at the time. So you don't have this problem to persistence instead of having like fish, a random like to flip a coin that you don't want the caused want to persists or knock off like if it's the TV like 15 memory cells are going to be here or whatever.
It's not the right way to do it because the material there are going to inject into patient would we arrived from patient to patient. If the patient has been heavily pretreated. We see for example, 10 wise or 11 lives of treatment with Darzalex is whatever elotuzumab immense et cetera.
And you come up and do want shots of the paid like you, making that raises the basin. The quality of your teeth us I'm not going to be are going to be sub optimal and you cannot exactly predict what's going to happen and thats why do you see most of these patients relapse. After a certain period of time. So I think it's better at the end to have a consistent protocol to the b the lumped in there.
And if you need to sell to stay for a long period of time, then give more so.
Yeah. Thank you so much for taking the questions.
This concludes todays conference I'll now hand, the call back over to Simon harness for closing remarks.
Yes again, thank you everyone for your wonderful questions and we appreciate your patience during the Q and a recession. We think this is important to spend a lot of time going to these and if you have any further questions feel free to just could mean email and we're happy to get back on the call, but again. Thank you so much and we're excited for the next two weeks and what.
To come.
Thank you.
You may now disconnect your lines at this time, thank you for your participation.
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