Q3 2019 Earnings Call

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

This call is being webcast live on the Investor section, a 47th website at Www Dot 47, Inc. Dot com.

Please be advised that this call is being recorded.

Following the formal remarks, well open up the call for questions.

This time I like to turn the call over the Michael her works with Stern Investor Relations.

Thank you.

Good morning, 47 issued a press release, you telling its third quarter 2019 financial results along with anticipated future milestones in recent accomplishments.

Although on the Investor section 40, 47th website at Www Dot 47, Inc.

Today's call will begin with prepared remarks by Dr. Mark came ish, Chief Executive Officer, 47, and Ann Rhoads, Chief Financial Officer of 47, then we will open the call for questions Dr., Chris talking Auto Chief Medical Officer, Dr., Marcelo founder and Vice President of clinical development and Mckool <unk> Vice President corporate development are also on the call.

And we'll be available for questions.

Before we begin I would like to remind everyone that statements. We make on this call will include forward looking statements. These students are subject to risks and uncertainties that could cause actual results to differ a description of these risks can be found in our most recent periodic reports filed with the FCC.

Any forward looking statements are made only as of today's date and we undertake no obligation to update. These forward looking statements to reflect subsequent events or circumstances I would now like turn call over to Mark.

Thanks, Michael Good morning, everyone and thank you for joining us today to review, our third quarter 2019 financial results and recent business highlights, which we announced earlier today.

In the third quarter, we continue to progress toward our goal of delivering safe well tolerated and effective treatments to patients in disease areas of high unmet need as you know our lead product candidate Monroe AMAP previously known as Fivenine is an anti CD 47, anti body, which seems to turn off an abnormal felt upregulated do not.

He'd be signal, that's enabling macrophages, the innate immune systems first responders to effectively initiate an immune cascade and promote abnormal cell, killing and long term defense.

During the quarter, we achieved meaningful progress across our pipeline, including our earlier stage programs that target other components of the Cds 47 pathway.

Alongside much roll them out we're advancing fs I want to eight nine or anti <unk> antibody and F. S. I won seven for our anti secret anybody in order to explore additional opportunities to more fully exploit the CD 47 pathway, that's a novel therapeutic target.

This morning's call I will highlight that progress across two of our pipeline candidates Mcgraw map and Fs I won seven four I will also remind you about coming next steps for each program.

Beginning with our lead candidate the grow about.

In the third quarter, we focused on preparing to initiate our first potential registration enabling trials in my we'll just plastic syndrome or Mds.

And diffuse large b cell lymphoma RTL bcl.

Following recent interactions with the FDA. We believe we have plans in place for both programs, which could allow us to achieve accelerated approval and to address the unmet needs of substantial patient population.

On today's call I want to provide an update on these plans and also elucidate what we consider to be the market opportunity from a girl a map in Mds and deal Bcl two of the hematologic malignancies with the highest burden of disease as measured by both annual incentive and mortality.

Let me start with Mds in the second quarter. We're now should we expect to take a two part approach to securing potential approval.

First we're expanding our ongoing phase one be trial, which uses a weekly dosing regimen of Mcgraw. The map in combination with a society to approximately 90 patients with untreated intermediate to very high risk Mds to accelerate the acquisition of 12 months safety data.

We continue to enroll patients in this ongoing single arm trial and the primary endpoint of that trial is overall response rate with durability of response.

We're also working with the FDA under a special protocol assessment to finalize the key parameters of our second trial, which will use up more convenient two week dosing regimen to evaluate the combination of roadmap and exercising in Mds patients.

We expect to complete enrollment of our first trial and the third quarter 2020 and to initiate our second Mds trial in the first quarter 2020.

In parallel we are moving forward with chemistry manufacturing and controls or CMC activities to support an expected filing of the B.L.A. in the fourth quarter of 2021.

Our confidence in Mcgraw, Matt and his decitabine in combination is buoyed by the data that continue to emerge from our ongoing phase one be clinical trial.

As we announced last week, we'll be presenting additional data from our ongoing trial and at the 61st American Society of hematology or Ash annual meeting.

These data include additional efficacy and durability data for a larger number of patients.

We're encouraged to see that the response rate we presented at ASCO in June 29 team continued to hold over time with 54% of untreated Mds patients achieving a complete response.

These data are particularly exciting and what they mean for patients living with Mds, while the MBS affects thousands of people a vast majority go on treated.

Approximately 75% of patients receive only supportive care or watchful waiting due in large part to the limited number of safe and tolerable therapies available.

Patients can choose to undergo allogeneic stem cell transplant, which as you know, it's a risky and complicated procedure or they can try by days a deck engine or revlimid, but these offer at an attractive risk benefit profile and low rates of response.

With Mcgraw them and we believe we have the potential to offer the first new therapy and over 13 years with a treatment that thus far as well tolerated and effective.

We're excited about the opportunity and look forward to providing additional detail on our phase one be clinical trial results and our future plans around ash next month.

Turning to deal Bcl as you know following receipt of Bhaskar guidance, we are planning to initiate a single arm trial isn't growing up in combination with rituximab in heavily pretreated deal Bcl patients with primary endpoints evaluating overall response rate, including Prs and Crs with durability of response.

In this trial, we plan to enroll approximately 100 patients who have failed at least two prior lines of therapy, which could include but is not limited to patients who are ineligible for car T therapy.

In line with previous guidance, we expect this trial to begin enrollment in the first quarter 2020, and expect that will be in a position to report interim efficacy data by the fourth quarter 2020.

In parallel we will continue to evaluate biomarkers for options to advance into earlier lines of treatment.

As you've heard US described before there remains a substantial unmet need and deal Bcl, even despite recent approval.

This is especially true in relapsed refractory setting where there is still a paucity of options that can be tolerated by fragile elderly are rapidly progressing patients.

Like in Mds, there's a clear and compelling need for safe well tolerated and effective therapy for people with deal Bcl and we're committed to moving Mcgraw, Matt forward as an effective option in this population and it's our lead focus for approval in deal Bcl.

To expand in earlier lines of treatment, we continue to explore biomarkers for potential predictive value and several triplet regimens in partnership with large pharma companies.

Importantly, the FDA has granted Mcgraw xmab fast track designation for the treatment of both Mds and deal Bcl, which believe speaks to encouraging efficacy data to date and the urgent need for safe and well tolerated new treatment options for these underserved patient populations, we believe that.

To grow about mechanism of action, coupled with its combinability with our other with other immunotherapies and Oncolytics and favorable safety profile offers a unique product profile with the potential to transform the treatment of cancer and empower patients to better fight their disease.

I want to briefly comment on a programs in solid tumors. We recently submitted abstracts that include data from our ongoing phase one be trial of Nicola Matt in combination with a value mab in patients with green cancer, and our phase one be trial and the gorilla Mab in combination with sex map in patients with colorectal cancer to major meetings that will occur.

Her in the first quarter 2020.

At those meetings, we plan to announce initial data from both studies at the time of those presentations.

Alongside all of these important effort, we're continuing to advance our pipeline assets.

Yes, I won seven four which charges targets. He kit NFS I won eight nine which targets or alpha toward the clinic and we remain on track to initiate phase one trial trials have both next year.

Earlier today, we announced our entrance into a collaboration with Bluebird bio to evaluate our antibody based regimen, which is comprised of Fs high 174, and grow a map with blue birds went to globin gene therapy platform for treatment of diseases that can be corrected with transplantation of autologous GE modified blood forming stem cell.

Okay.

This partnership represents a critical step toward our own see QIP program and we're excited to work with Blue Bird a leader in gene therapy to evaluate opportunities to improve treat pre transplantation conditioning.

As you know most ex vivo hemo.

No matter, what extent cell transplant and gene therapies require that a patient's own stemcells first be depleted from the bone marrow two facilities in graph much of the new hematopoietic stem cells or hfcs through a process called conditioning.

This process typically requires the use of chemotherapy with or without radiation exposure, which can induce sterility acute infections, prolong hospitalizations and increased risk of emergence of secondary malignancies.

As our hope that our novel antibody based conditioning regimen, which requires neither chemotherapy nor radiation could avoid these toxicities.

Our scientific founders observe that blood, forming stem cells, which uniquely express sicad can be targeted by F. ESI ones have been for once Fs I won seven four binds hsbcs co treatment with Mccullough map releases macrophages to attack and clear these to himself.

Based on these observations coupled with the results of preclinical studies, we believe the combination of SFR.

One seven for and the Gorilla Mab could offer an important and improve conditioning regimen with more selective and short term antibody mediated clearance of hfcs.

It is our hope that this could massively expand the number of patients eligible for transplantation and therefore enable many more people to benefit from that curative potential of transportation.

At Ash, we will be presenting a poster, including new printed preclinical data for Fs I won seven for this poster details the results of non human Primate studies in which we observed that the combination of Mcgraw Tomorrow and Fs high one seven for significant significantly depletes the frequency of bone marrow hfcs.

Compared to placebo with no change and peripheral blood cell counts over the course of the study.

We believe these data demonstrate the specificity efficacy and safety of the combination in a highly revland relevant preclinical model.

Based on these results we are eager to initiate our phase one healthy volunteer study of ESI. One seven for early next year and then start our combination trial was bluebird if successful we hope to explain expand beyond genetic blood disorders, two other transplant setting such as allogeneic.

And other tumors.

We with that I will turnover.

The call to add to review our financial results for the third quarter 2019.

Thanks Mark.

We ended the third quarter 2019, with cash cash equivalents and short term investments of $166.7 million compared to $139 million as at December 30, Onest 2018.

This increase reflects aggregate gross proceeds of approximately $86.3 million from our underwritten public offering of common stock that closed in July of 2019, as well as an approximately $15.7 million upfront license payment from our entry into a collaboration with all know pharmaceutical.

We believe we are sufficiently funded to support our planned operations and capital expenditures through the end of the first quarter of 2021, which is beyond anticipated interim data readout from almost all of our ongoing clinical trials, while also investing in our earlier stage pipeline.

Now turning to the third quarter 2019 income statement.

During the third quarter, we recognized $15.7 million in revenue due to the license granted under the on our agreement we did not record revenues on the third quarter 2018.

Also during the third quarter, we incurred $27.1 million and research and development expenses compared to $18 million for the same period last year.

This was primarily due to a 9.2 million dollar increase and advancing our current clinical programs focused on Mccolo map.

And the associated contract manufacturing cost far B.L.A., enabling studies.

3.2 million dollar increase in preclinical program costs.

At 1.5 million dollar decrease and funding recognition under the California Institute for regenerative Medicine, and Kimi on lymphoma Society Grant.

As well as a 1.1 million dollar increase and personnel related costs.

Partially offset by 5.9 million dollar decrease in license fees, primarily due to the nonrecurring license fees paid under the blank asset purchase and sent on license agreements in 2018.

Our general and administrative expenses were $5 million for the third quarter 29 team compared to $4.4 million for the third quarter 2018. This increase was primarily due to a 400000 dollar increase and personnel and corporate related costs driven by an increase in head count.

Our net loss for the quarter was $15.1 million or 38 cents per share as compared to a net loss of $21.7 million or 71 cents per share for the third quarter of 2018.

With that I'll now turn the call over to the operator for questions.

Ladies and gentlemen to ask a question you would need to press star one on your telephone.

Draw your question Reston town key please standby we've compiled acuity roster.

Our first question comes from Michael Schmidt of Guggenheim Securities. Your line is open.

Hey, guys. This is Charles do on for Michael Schmidt, Thanks for taking the questions and congrats on the progress a first one from me up within Mds, what kind of a patient subtype breakdown for example between intermediate or a very high risk patients would you expect within these trials and could the benchmark for approval change based on Sept breakdown.

Hi, This is mark sorry, thanks for the question so.

We won't be as Weve reported Oscar but will be reported on a sharp wrote down a patients enrolled that our intermediate high and very high risk fraud upsets, that's our culture, which.

Constitutes our breakdown of entry criteria.

Per prior discussions we have seen a very balanced enrollment for both intermediate although we have to very high risk, notably this in our previous presentations, we've had a fair percentage.

Patients with course hydrogen added risk factors to Richard Denver to.

Predict or poor prognosis with regards to potential approval again, we believe that this criteria as well and based on or after discussions with sufficient for potential registrational population.

Sure anticipated that that's a Dan aren't vision criteria were kind of going forward in our registration studies.

Got it makes sense could you also remind us why youre looking at both the twice weekly in addition to the once weekly dose and the degree to which you'll need data from both trials or if you have an approval pathway based on one of those trials. Thank you.

Hi, Charles this Mark Mccamish. This relates to the ongoing expense experience, we've had with M.L. transitioning into Mds and with ammo. We used weekly dosing as these patients written the hospital very often for transfusions and other treatments and as we have then progressed to Mds.

These patients are less often in the hospital and using a less frequent dosing is going to be much more convenient we ought to be able to provide the best option for these patients to be able to penetrate the marketing and benefit them. So we track we're transitioning to the every two weeks dosing in our second trial. So that we have the option of using.

In the commercialization of this of this product, which we feel will allow us to penetrate a larger segment of the of the market population. We've already looked at pharmacokinetic evaluations of this over time and this is very similar to the dosing that we'll be using India Bcl. So we're very comfortable with using that to every two weeks dosing.

Understood. Thanks for taking the questions. Thanks Ross.

Our next question comes from Matthew Harrison of Morgan Stanley . Your line is open.

Hi, Thanks for taking my questions. This is Jeff I'm from MISO Harrison.

My first question is could you give us an idea of how many more patients and.

Kind off duration to expense at ash from the Mds cohort.

Sure. Thanks for the question.

So with the ongoing phase on the study where continue to be pleased about better robust enrollment of its has been very soon with our investigators.

Because again solutions are considered to enroll and as well as our intention to want to talk to the most recent data we will be providing.

Great data Hi, right ahead ash oral presentation I'd because of that it's we're unable to provide exact guidance numbers on positions and follow upon but we will have additional patients from what is presented after your initial ash abstract I was released last week I will also say that as we grow our David said.

We will also be looking at a position sub analysis.

I wish we started or what that nutritional or responded by nutritional subtypes of which we highlighted since we took you through so we will continue to provide such that a.

<unk> presentation.

Okay, great how bad the duration.

Yes, so we will be following these patients obviously for longer and that would be another two outbreak.

It's because patients are enrolled continuously it's hard for us if you haven't per that in fact original followed by data. We do believe that's a key important factor when we provided updated data on are pushing it up and ROE.

Okay. Thank you very much.

Second question is could you give us any.

Any guidance around the process with the ASP for the second Mds people to study.

So what is the level of progress with the FDA and how many issues remain that you need to clarify.

Yes, we've been having an ongoing discussion with FDA under this special protocol assessment to provision and that involves both.

Teleconference calls as well as in person meetings with them and as you can imagine there are several components that were discussing including primary endpoint.

Justification.

As well as the potential of the effects of the growing Matt.

In monotherapy as well as were tux mebane mono suits Humane society in monotherapy, so with those.

Pretty good historical preference.

Information about Asia, and monotherapy less information.

About them the gorilla map in monotherapy and so we're discussing those those issues as well as how we provide data around that so it's an ongoing discussion and we expect that to be wrapped up in the next quarter. So.

Okay. Thank you how much.

Thank you.

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

Frankly, you're asking the question.

I'm not sure Bcl trial on the indicated that <unk> completed the.

All right inclusion exclusion criteria for those.

Provider for little bit more color around what would constitute good Clarkson your ineligible patients within the context of Oh that population you plan to enroll and then secondarily on the rubber collaboration.

HM.

Sure thing mechanism around your combination of Hmm and <unk>.

[laughter] tomorrow, thanks for the question.

Regarding your question about the eligibility criteria for the deal Bcl study just to be clear, we are not mandating that patients the car T ineligible as we go forward right, but we are including patients who may be car T ineligible.

And then we will be collecting the reasons why they are car T. Ineligible, we know from our past phase two experience that they're a variety of reasons that range from medical reasons.

For being on set for says things like socioeconomic insurance reasons geographic reasons as well.

We are not focusing just on the car T eligible population, losing for right of course, but will you be able to look at those different buckets or and eligibility sort of medical courses are there.

Yes, and that's actually something that Weve looked at very closely.

In our current population.

And Weve identified that there are patients, particularly patients that are elderly and more frail, who actually do benefit from our therapy again, our favorable safety profile really.

Actually fits quite well with that population and we have seen benefit I would say the one population that is car T.

Eligible that doesn't seem to benefit from.

Therapies in general are those who are rapidly progressive.

And our having disease, that's progressing very rapidly and cannot wait for car T therapy, but overall, we were going to be looking at this probably.

Okay, and then more on your on your second question regarding the dosing around see kit as.

As you know the the goal here is to clear out the hematopoietic stem cells. So we we dosed with.

Both five ask nine as well as.

The anti see kit, what we do as we use the priming dose initially with Fivenine, followed by a therapeutic dose and that therapeutic doses given with the anti see kit and the goal is to then clear out the amedica extend ourselves so.

The anti Sicad labels and met appendix themselves then.

The Fivenine frees up.

Macrophages to attack and clear those.

Where we worked out the PK and non human primates that we'll be talking about ash.

And the important component is to ensure that you give enough to clear out the medical clinic Stemcells and then allow for those agents to be eliminated.

Prior to transfusion of Eugene modified cells, and we'll be talking about that at ash as well that's the primary focus.

Alright, thank for that.

Thanks Maher.

Our next question comes from Robert Hazlett, a B T. G. Your line is open.

Hi, guys. This is Jay Colby on the line for Bert Thanks for the question.

I just wanted to follow up on the asset Ash abstracts will you be breaking out I guess, the first 11 patients that we saw at ash just to get over a longer term duration a follow up there acknowledging that a lot of patients will be enrolled recently.

Yes.

Thanks for the question. This is March Arthur I. Appreciate the comment we will be a detailing out our dad importantly, as you mentioned follow up for their associates and as you alluded to since we will have recent patients enrolled that may not accurately capture the duration of follow up for their initial position. So we won't get an attempt to do everything thats really important.

I've been pleased to see a at least as of the ash abstract announcement fabric uncertainty Knox's a median duration of response with additional follow up median wise, our various will be dead or will continue to present for both the initial and observations as while you have just patients and nutrition I come onboard.

Okay, great. Thank you for that and just a follow up is based on your kind of your discussions with the physicians and maybe some with the FDA. What do you think is a clinically meaningfully differentiated duration of response or five that's nineties.

Yes. Thank you.

Sure. So I think about fits our data first so adds as you know from our abstracts presented last big reason for years to see about the advocacy is considered to tracker, notably we see CR rate of 54% and again seeing on regulatory endpoints.

I've stated SCR plus PR rate, we believe it's meaningful for Registrational approval with regards to in terms of white would be a credit clinically meaningful benefit I think part of that from a regulatory approach as well as clinically is being able to exclude watch is as I have decided in monotherapy responses are we've guided that a bit.

And the 2004 label 40 decided in an NDS and that the CRP Vice Chairman is were 16% Richards fairly while I. So we believe that provides a bar converse and everything in terms of demonstrating the combination over decided as monotherapy.

Thank you congrats on the progress.

Thanks Jay.

Our next question comes from Sean Lee of H.C. Wainwright. Your line is open.

Good morning, guys and thanks for taking my questions.

My first question is on the upcoming Mds pivotal study so I understand you're still working through the details as the U.S.K. with the FDA, but I'm just wondering other than the.

Change to dosing regimen are there any additional changes proposed for the patient populations and also has the FDA signed off as calling on the objective response rate of Steve.

Point or are you looking for stuff like a PFS as well thanks.

Hi, Sean we continue to work with the agency on this the population that we'll be using is no different than what we've proposed previously so that's been too much discussion regarding that.

And then primary endpoints.

As we've mentioned previously.

Nomination of PR NCR.

And we'll continue to discuss with them. The most appropriate approach as we move those forward I think a detailed in the answer to my two other questions.

Some of the issues that we're discussing and not anything that's surprising in that situation study design number patient statistical approach et cetera.

And the major change of course is the every two weeks dosing I think was our experience and the first study and weekly dosing I guess is quite a bit of information to be able to hone in on most important components with the agency and that's an ongoing discussion.

Great. My second question is on the.

Collaboration is bluebird, so could you provide a little bit more color on the financial aspects of that and who will be responsible for running the upcoming phase. One studies next year and also existing purely a research collaboration or are there any options or exclusivity associated with it.

Sure Sean I'll have an accrual a jump in since he has worked out the agreement.

Thanks, Mark So yeah. This is the research collaboration is solid we need to find period.

The research collaboration is designed around establishing a proof of concept for antibody along with Blue Bloods gene therapy product.

And so.

The way the collaboration would work is that each bucket wouldn't be responsible for its part of that as such plan.

For us for 47, it wouldn't be we wouldn't be responsible for the preclinical studies the filing for the I'd and also the phase one healthy volunteer study.

And then bluebird wouldn't be responsible for the proof of concept and each bucket would bring it product into the collaboration and also do cost shedding let's talk about.

And as we move forward as Michael mentioned, we'll be doing the phase one trial and that phase one trial within normal healthy volunteers with our anti see kit, we have copious experience with Mcgraw Hill, a map and this is designed as a combination program. So that you you see kit that labels Hfcs and.

Then mcgraw them, which enables the macrophages to then attack so the phase ones fairly straightforward and normal healthy volunteers to confirm the PK and approach will be using with our anti see kit, allowing us to then move into combination where we'd be working directly with.

With Bluebird in their approach.

Thank you for the additional color that's all I have three.

Thanks, Sean.

Our next question comes from Adam Evertts of life that capital Your line is open.

Great. Thank you first question I know, it's difficult to comment on other companies programs, but maybe if you're willing it would be interesting to hear your view on the ash abstract data from Celgenes anti CD 47 sort of maybe what that means for the space or for the growing up specifically.

Yeah. They thought I'm a this is march there.

So we can provide a little bit of color I think as you alluded to there are few.

Programs that presented at the time city 47 targeting agents, a one of which results in a and then also another comment and Alex oncology I think overall our viewpoint is originator are pleased with interest in there. It's program rescinded then that is valid is the target.

Programs did show a evidence of efficacy I think again with regard to the Celgene data, which was interested in essence, one of the things up at slide was a high rate of anti drug antibodies that number is further abstract appeared to be effective biopsies southern potential safety. So that may also be initiative Rick.

Program I think what we think there was just comment in terms of our program. We've been quite we've been deliberate as you know to define the most optimal opted in molecule to balance boasted inappetence. His answer there we treated over 400 plus patients.

And then really not seen any significant surged issues. We've worked around the non targeted in there with our timing amendments to our strategy as you know I think with regards to our and tried to antibody rates they have been quite low.

Less than 10% in our previously reported data without any evidence of any safety issues or pieces.

Changes so that is something by the end result, this differential.

And then Dan I'm just highlights.

Purchase that one needs to surgery in effective Retardancy 47.

Yeah, I think Adam we were pleased that others are interested in the program. It does validate the targets and it just.

Displays the experienced that we've had in this with our founder as it goes back over a decade, which really allowed us to make progress and anticipate some of the issues that others have run into so I think on both of those areas, where we're pleased with the emerging data and look forward to sharing our data as we go forward.

Great and then a quick question actually on the Ono pharmaceutical agreement I realize it's relatively recent but maybe if there any update there in terms of one Oh no might start a clinical trial in Asia and if they might participate in either of the ongoing or planned studies using Asian sites.

So let me just comment on that or an overarching themes as you know with owner there they're very interested in moving this forward in general the approach that that you use in partnership with A.

Japanese company is to provide a phase one data in the Japanese population and so thats. The most urgent thing that there will be working on this should provide a information in the Japanese population that there's no differences in PK intolerance and.

With our agent and then secondarily.

As we've mentioned previously one important component to both Mds and deal Bcl is how do we move forward with either confirmatory randomized controlled trial or randomized control trials that will address.

Next U.S. participation and we're working with Ono collaboratively in that in terms of the approach we would take forward in a in MBS and deal Bcl.

Thank you.

Thanks, Adam.

Our next question comes from Tony Butler Roth Capital Your line is open.

Thanks, very much three very brief questions and fairly simple number one is.

Mark just got to get to comment I think the filing pathway that you've laid out for these two studies very clear question is can you just speak about.

You and your thoughts there okay. That's number one number two is.

I'm just curious in the healthy volunteer study with see kit.

Is it pretty easy this might be a silly question, it's pretty easy to enroll patients who want to be immuno suppressed.

You know with the combination of agents and then allow just three gross of their reconstitution of their immune system just naturally.

And that's number two and then number three is.

More theoretical again and this is just back to the simplicity, if you don't need me signals.

The question is around just a deficiency and does Vista player will either.

By being deficient or then and then being prolific [noise].

Does that play a role and whether or not that balance between me and don't get me signals exists. Thanks very much.

Hey, Tony Smart grid cameras. Thanks for your questions and none are ever easy with you. So [laughter] appreciated so first on the E U S important question.

And we know that the EU is less likely to move forward with single arm approaches that are there and we're beginning to have discussions in terms of our approach. Obviously, we're looking at this as to how do we best coordinate and expand outside of the U.S. for commercial approaches.

And it's likely that a randomized trial would be required and that's fine because we'll be using that for confirmation in our approach is here in the U.S.

So we're beginning to have those discussions and one of the issues with any type of randomized control trial is do you simply confirm your findings or do you expand your findings and we'll have to discuss that is.

We would really like to get into lower risk Mds patients and one we'll have to decide whether you do that.

In a joint to trial with low risk and intermediate to high risk or what do you have two separate approaches to expand those those labels. So it's not easy, but we're discussing those and we'll be discussing with the.

Relative country agencies in Europe too.

Come up with the best overall approach.

The second question was on the secret normal healthy volunteer study.

Let me just walk through that a little bit.

And that is recall that anti see kit alone.

Well not clear these stemcells just labels the stem cells with an eye Gigi one and our non human primate data.

That we will be talking about at ash, well lit lay this out fairly clearly in the past it is possible to use an anti see kit.

And to use that in immunocompromised patients and be able to clear out.

He Metacritic stem cells, we have found in immuno crop immuno sufficient patients that the anti see kit alone does not cause clearance of those HFC. Therefore, that's the reason we use a combination so the normal healthy study that will be performing will only use anti.

Kit to document the PK.

Safety intolerance of anti see kit will not use the combination of anti see kit and fivenine or mcgraw them out in normal healthy volunteers as that would cause clearance.

Of these normal hematopoietic stem cells and would not want to do that in norm in healthy volunteers. So we'll use the combination in patients who will then be transplanted, but we'll use fs 174 or.

Our our anti see kit only in normal healthy volunteers and the third question I'm going to have March I'll take a shot at that have been starting for the time to the question. So with regards to your question about those Vista played a role.

Backtracked on highway I think one of the things that we.

Really like about to 47 target enrichment roll them out is its ability to your actually stimulate the adaptive immune system and so as you know we've discussed before we have preclinical and some evidence of clinical data demonstrated in bad.

Upon our administration Motorola macrophages can ingest cancer cells and presented tumor associated antigens to T cells, and activate and adoptive T cell response.

So I do think that then in that regard with other T cell checkpoints by Vista or PD, one there may be a role as well or we and others have demonstrated combination data in preclinical models with PD, one PDL one block C plus 47 losses. So I think that's important and then to your question about Vista I think there.

Essentially it could be a role there as you know Vista is expressed on tumor infiltrating lymphocytes has a role on to your T. Reg cells as well we've shown some evidence pre clinically that you also can and modulating downright there is a regulatory T cells. So there's certainly has the potential role I think it again highlights back in addition to and then we're going to evade immune system. We also.

And your hobbies adaptive immune system and then with regards to weather Vista plays a role I mean, you're at Arnie.

Cascade I think thats, having met so means that the universe.

Thank you very much for the clarity I appreciate it.

Thanks, Tony.

Our next question comes from Mark Freedom back of Oppenheimer. Your line is open.

Hey, guys. This is not on for Mark. Thanks for taking my questions are congrats as well in the Bluebird collaboration so just want from us actually and I apologize if I missed this in the prepared remarks, but one of the main drawbacks, we commonly here about bluebirds approach with diesel thing its effect on sexual reproduction and we're just wondering if you could.

Kind of shed some light or give us your expectation for whether you think your approach should be safe round gametes. Thanks.

[noise] Yeah methods. This is mark sorry. Your appreciate the question. So I think you bring up a really important point.

Is that standard conditioning regimen cytotoxics like you solve their which is widely used for mediaengine therapy cannot only ties kind of morbidity in a short term their potential mortality, but importantly long term effects. So I think infertility and effect on sexual reproduction is a major issue, especially for young patients today.

Her position that.

Our debt engine therapies, and other transplants for lessen sickle cell or urban in California. For example, I think based on our knowledge.

And 47 blocks. They did an antibody based approach we believe that this antibody in combination with these safer and perpetuated not have those risks of infertility secondary malignancies, which I don't really important for patients to determine whether they want to go for transferring or not so we do think that these are potential.

He areas of safety benefit.

There is competition, our conditioning regimen that will allow for patients and clinicians to have a better option to choose I should our that are unsure about so thanks for that question and again, Matt. This is mark how much will also have preclinical data is required for the I, India, which include talks information and that will back up what market.

Thing is that there is limited risk from a standpoint.

On this Forster Realty.

Awesome looking for good at Ash, Thanks, guys.

Thanks, Matt.

Our next question comes from Sumit Roy Jones trading your line is open.

Hello, everyone. Thank you taking the collection.

This was a touch upon the expansion of enrollment criteria in but yet bcl trial.

Could you just talk us through that decision, making process, while you income.

You could.

Listen to compete competitive.

Detail in that space, given your feeds licensees to come combined keeps a CR up 18%.

Who versus a car T up.

Hi, turkeys to 14th.

Q2 reasons.

You think that sponsor equity improved flow with certain patient group. So.

I understand you're sitting on it.

Yes. So at this is Mark Mccann first let me just walk you through a little bit of this and then Chris can can backup as well. So the processing was involved both our phase one phase one being faced two patients are ongoing discussions with FDA.

And what would be best for patients moving forward.

And as you know Weve initiated these programs in patients who are relapse or refractory to rituximab treatment.

It's important.

That you understand there at the differences with the approach, we're using which augments 80, CP versus ADCC, which is the initial mechanism for rituximab. So we can rescue patients had been previously treated don't respond to redux ma'am.

But it's also important to look at lines of treatment and how others are impacted by all of these and we've looked at data from our phase one be phase two studies as well as interface with the agency and as you can recall when we talk with them after our initial meeting.

It was presenting the data they were giving us guidance regarding the approach to a single arm trial, a randomized controlled trial is not is not an issue. One can describe a standard of care approach, we can take and move into that however, with using a single arm trial approach.

They were guiding us in terms of the patient populations that would differentiate us from other agents.

And initially they were interested in the.

Car T and eligible patient population because they knew that this was a fairly large population and there were various reasons one could be Cartesian eligible we explored that in our phase two component and then have a good understanding of that and our latest discussions with the agency and walking through this.

We felt that car T and eligible and using the descriptor of that was limiting.

And when we looked at all of our data from the phase one being phase two we felt that using a definition that would be greater than two lines.

Cdtwenty treatment.

Regardless of whether they risk car T and eligible or not would allow us to have a patient population that would be along the line of third line patients and that would respond as we've outlined in our experience with greater than three lines of greater than equaled three lines of treatment and that patient population. So weve interface to assess the.

Agency, we've looked at our data we've looked at translational data to understand the responses that these patients would have and we think we've got a reasonable understanding of that and and.

I have agreed with the agency to move forward in that.

Greater than second line anti CD 20.

That could include car T and eligible but is not required to be karkhi ineligible and we think that gives us the best opportunity to have an impact on the patients that would boat that would most responded to our agents.

Yes, no I'll just add that in our comprehensive review of the phase one and phase two data very clearly there are these patients that had a very strong benefit from role in that and Retex, Matt and again. Many of these patients had even three or more prior lines of therapy before coming onto our study many of them.

Were primary refractory so there's very clearly a population here that does get a very good benefit with durable responses and our plans to move forward is to really try and and capture those patients.

Got it.

If you could just remind us what person to lead the car T. Eligibles in New York piece I want to combined and I would just second question is.

Which we go to in the solid tumor program.

Cmos.

It appears targeting seek late seem to your signal things.

Active so.

Hello.

She what types like lung cancer type do you think you would focus on something more.

You mean package types, rather than the ovarian and CRC, which is obvious at October .

[noise] Sumit I'm, having a little bit difficulty hearing your first question could you repeat that first question. Please and lets call. The first courseware I just want to ask what percent in your feeds want to study where coffee in eligibles.

It.

So I can address sets in the phase two population essentially the vast majority all those patients are nearly all those patients where Cartesian eligibles because that was a mandatory requirement in the phase one population we did not capture.

At the car T ineligibility status there in because high teen eligibility oftentimes is a very subjective determination based on the treating physician we can't give you the specific breakdowns in the phase one population.

And then see assuming that this is much harder to your second question with regards to there are kind of hot or cold tumor types and as hot Summer program.

So we are looking at that approach I said, John as mentioned on the call. We're programs in ovarian center, which is more consider cold tumor type redo of note.

A combination with hasn't wasn't bad that's run by genetic and clinical collaboration in bladder cancer.

That is as you now more hot.

After tumor types are really per about hypothesis asset that study ongoing reducing that Paul tumors is in.

Thats on top.

In addition, I think what are the things that we're seeing in terms of class competitions as with our data with you decided in and other preclinical data that received with Cytotoxics or chemotherapy up regulated and let me say no immediate synergies this would likely a pilot we never pre clinically to your other chemotherapy combinations. So this may be a strategy.

Total value with combinations with might roll them out, especially in the solid tumor setting and while I'm not likely cancers.

Thank you so much for taking on the question Congrats again.

Yes.

Thanks.

There are no further questions like to turn the call back over to Mark Mccamish for any closing remarks.

[noise]. Thank you all and operator, thank you.

We really appreciate you taking the time to join us or early in the morning and for your continued support of 47, we look forward to updating you again soon thanks again.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.