Q2 2019 Earnings Call
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Hi mother conference.
[noise].
Good afternoon.
Yes, Your conference I'd or the name of the conference.
Prime.
Physics.
During the spelling of your first and last name.
Our a C H E L first name Rachel.
Smith.
Aim as am I T H.
Company name again.
An I.E.R.A.
Yeah.
Q rejoining the substantial increase in the beam a commercial opportunity in the United States, Europe , and Asia regions versus our original expectations.
Altogether, we continue to be excited about the potential for bema to be an important new medicine for patients with gastric cancer.
Turning to FP 150, ESMO has accepted our abstract and we will present data at the upcoming annual meeting in September .
We expect to present data from the monotherapy phase one expansion cohorts at the 20 milligram per kilogram dose in patients with breast ovarian and endometrial cancers over expressing b seven each for.
While monotherapy data will be the focus at ESMO, we believe based on preclinical data that FP 150 hold significant potential in combination with other checkpoint inhibitors or chemotherapeutic agents.
On that front, we're approaching completion of the safety lead in for the combination of FP 150, with Keytruda and expect to open the ovarian expansion cohort later this month.
If we identify efficacy in the breast or endometrial monotherapy cohorts. We may also begin additional chemo and our checkpoint combination studies in those indications.
Turning to B T 155 enrollment is proceeding according to plan in the dose escalation portion of the phase one trial with six dose level cohorts enrolled and dose escalation continuing.
We have submitted an abstract to present dose escalation safety and pharmacokinetic data from this program at 50 in November .
For our partnered programs completion of enrollment in the randomized phase two trial of Kabira and Opdivo in second line pancreatic cancer is imminent.
And we expect Vms to have actionable data by next year.
BMS is the trial sponsor and we'll determine when it's appropriate to disclose data and next steps for this program.
And finally, BMS 96, 258, a fully human antibody targeting Tim three and immune checkpoint receptor continues to advance into phase one two clinical trial and is now being studied by BMS in combination with Opdivo.
As I mentioned earlier, we are preparing for several upcoming data events that will allow us to make disciplined data driven decisions to prioritize pipeline investments and with that I'll turn the call over now to Helen.
Thank you Aaron.
Let's begin with Bema building on Aaron's earlier comment the reason to add an early futility analysis to the fight trial is to ensure the trial is adequately powered to detect an overall survival benefit at full enrollment.
I'd like to remind you the fight childhood double blind placebo controlled trial, which means we don't see the unblinded data.
There is an independent DMC, which he does reviewed the unblinded data at our last meeting with them. They recommended continuation of the trial without modification.
The trial continues to enroll very well and we continue to see globally, a prevalence of MTF are to be in the frontline setting up over 30%.
In light of rapid enrollment and our desire to manage our resources wisely, we're planning to pause enrollment in the fight trial during the fourth quarter.
We estimate that by the fourth quarter, we will enrolled approximately 25% of the total planned patients which should be sufficient to generate the number of events needed to conduct a futility analysis in the first half of 2020.
The futility analysis is a crucial de risking event for the fight trial as once we know the outcome of this analysis, we will be able to make a data driven decision why the resume enrollment and the trial or discontinue it.
Beam has a well tolerated targeted monoclonal antibody demonstrated single agent activity being used in a biomarker selected patient population and we remain optimistic about the potential for being made to improve the survival of patients in frontline FGF art to be over expressing gastric cancer.
Moving on to FP 150, which is our first in class B seven each for antibody. This antibody designed to target tumor south through two mechanisms of action by enhancing killing a b seven each for over expressing tumors do enhanced ADCC and by blocking be 784 from sending an inhibitory signal to CD eight T cells.
We plan to present preliminary data at ESMO from approximately 30 patients pre selected for B seven each for tumor over expression across the ovarian breast and endometrial monotherapy expansion cohorts.
This will be early data as most of these patients will have had a single scan and only a handful would have been on study long enough to have had their second scan.
We also anticipate having safety data from the first four patients enrolled in the combination cohort of Keytruda and FP 150.
Our preclinical data for FP 150 demonstrate seeing synergy with anti PD one.
Additivity with chemo and modest activity as a single agent for this reason, we believe the ultimate development path for FP. One FP 150 will be it's a component of combination regimens similar to how other monoclonal antibodies directed to solid tumor targets are used for example, herceptin and prijedor are used in combination with chemotherapy.
In May we initiated the combination dosing in a b seven eight for selected ovarian cohort with full doses of both F 150 and Keytruda.
We anticipate completing the safety lead in and opening the Keytruda combination expansion later this month.
Which should generate efficacy data to make a go no go decision in 2024, the FDA Onefifty keytruda combination in ovarian cancer.
Turning to F. B T 155, the dose escalation is proceeding according to plan and we expect to present, the first available safety and pharmacokinetic data from the initial dose escalation cohorts at city in November .
As you may recall, an antibody that activate T cell through CD 28 resulted in Super Agonism, and severe cytokine release syndrome.
By contrast, preclinical data demonstrates that F.P.T. 155 requires co stimulation for T cell activation, and therefore should not trigger Super agonism.
The reporting early safety Tolerability and lack of cytokine release syndrome at early dose levels will support the key differentiating features of that P.T. 155.
Aaron has already provided you with an update on the partner programs. So I will now turn the call to our CFO David Smith.
Thank you Helen.
The complete details of our financial results for the quarter can be found in the press release that we issued earlier this afternoon and on our company website.
We ended Q2 with a strong balance sheet cash cash equivalents and marketable securities totaled $214.1 million on June Thirtyth 2019.
Compared to $237 million on March 30, Onest 2019.
This expected decrease over the prior quarter reflects operating and other expenses during the quarter that exceeded revenues. The net loss for the quarter was $34.4 million or 99 cents per day per basic and diluted share.
This was flat with the prior year.
Collaboration and license revenue was $3.3 million for the quarter. This is a decrease from last year's second quarter revenue of $7.6 million and was expected.
It is primarily related to lower collaboration revenues from Bristol Myers Squibb as a result of the completion of the research term under the immuno oncology discovery collaboration in March 2019.
Research and development expenses were $29.4 million for the second quarter of 2019 compared to $33.4 million in the second quarter of 2018. This decrease was primarily related to lower compensation costs as well as lower manufacturing costs related to F. P. T 155 drug production and lower diagnostics costs related to the fight trial. These cost reductions were partially offset by higher CR all costs that were related to strong patient enrollment and the opening of new clinical trial sites.
Gionee expenses totaled $9.7 million, which were essentially flat year over year.
Looking ahead, we continue to expect full year 2019, net cash used in operating activities to be in the range of 117 million to $122 million, we estimate ending 2019 with approximately a 148 million $253 million in cash cash equivalents and marketable securities.
In closing we have the resources that will take us not just through but beyond go no go decisions for the fight trial FDA Onefifty, an F.P.T. 155.
Now I will turn the call back to the operator for today.
Thank you.
Ladies and gentlemen, if you have a question at this time. Please press Star then one on your Touchtone telephone.
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Press the pound key again that is star then one if you would like to ask the question.
Our first question comes from the line of Jonathan Chang with SBB Laurie.
Your line is now open.
Hi, guys. Thanks for taking my questions.
First question can you provide more color on the rationale for pausing enrollment in the fight trial when you've been long enough.
For now.
Let me now.
Yes, Hi, Jonathan This is Alan yes, absolutely I mean, I think we.
At the last.
Quarter call, we talked about adding a futility.
Based on seeing such a high number of patients qualifying for the trial and wanting to make sure that while we thought all patients have a scientific rationale to benefit from BMS.
Obviously, we need to make sure that the trial is powered such that that when we complete enrollment we will be the trial will be successful so and at that point, we were a little bit vague as to when that would happen because we didnt, we were still ramping up sites in Europe .
And and really hadn't had any events yet so now we feel like we're at a point, where we know when we want that futility or one that futility can occur and then again because enrolment so quick.
We think it's prudent for our company that we end up pausing enrollment observing written a futility and then resuming enrollment I'm presuming that we pass so I think it's really a matter, maybe and you'd like to add to this about.
About you know also all of our with the rest of our portfolio.
The other element here is.
Fiscal discipline exercising with respect to the portfolio I think once we see whether this event.
Becomes the de risking event, if we pass them, we would be in a position to the rest of the resuming enrollment we have drug supply ready to go.
And I think we'd have investigator enthusiasm.
Passed futility, yes, and you can imagine Jonathan your patience you enroll say after Q4 and until you read out that futility are going to contribute to that futility. So.
Of course, yes, it'd be nice to have those patients let me resume but everything.
You know the trials open it essentially all the sites you want to be open that into rolling very quickly and we feel confident we can resume things quickly.
Got it thank you.
And second question can you provide more granularity on how enrollment in the phase progress versus your initial projections.
I heard you correctly, you indicated 25%.
In the fourth quarter.
How does that come there to your initial plan.
Yes, we didnt ever give exact.
Projections publicly about about our enrollments, we made analogies to the token trial you may recall that where if you go back and look at the Toga trial, which is now 810 years ago that it took them 36 months to enroll the trial that was fairly similarly sized and of course, there's a lot more competition out there. But then we also have access to China through ours I partnership. So so that was kind of the big guidance that we gave previously in and I can just tell you that we're ahead of that schedule. So.
Got it thanks for the additional color for taking my question.
Thanks, Jonathan.
Thank you. Our next question comes from the line of Steve feed House with Raymond James Your line is now open.
Yes, Hi, this is more of an anchor on for Steve seat House.
So we have a couple of questions about the mom.
So in terms of this potential futility analysis have you settled on the hazard ratio threshold.
That will be used and could you talk about some of the factors and how you will be choosing that that ratio. Thank you.
Yes. This is again Helen I can I can start with that and then Aaron can jump in.
So we Havent said what it is this is obviously a few.
We we have a recommendation that we will be making to our DMC, but there was a conversation that that has to occur there. What we do definitely want to do and plan to do and there should not be an issue and doing is making sure that that hazard ratio is less than one so sometimes you may see.
Trials designed where an early futility the hazard ratio is set at one and essentially what they are trying to do is very early on just make sure that drug isn't worse than placebo were not concerned about that right. What we really want to do is make sure that we're on track to show benefit so.
And to make sure that this trial again with its 540 550 or so planned patients.
It's powered to achieve its endpoint so.
And you want to add to that.
No I think that answers it thanks.
Okay, Thanks and.
Our next question.
I guess could you talk a little bit more about the process.
That informs you about the enroll patient characteristics and the FEMA trial I mean, it sounds like you have a pre specified plan and it sounded like you had another checkinn recently and could you talk about the proportion of Asian population that you're seeing now versus what you saw in the first 100 patients I believe it was 100 patients that you looked at.
Originally thank you.
Yes, I cant off the top my head tell you what proportion of patients our China ex China Asian U.S. our European.
I can say that just like we saw back and talked about at the at our Q1 call that we are seeing a FGF are to be over expression prevalence in the frontline setting that is similar globally. So there's no difference in the different geographic areas.
So its and then as you may recall, what we talked about at that point was that we are seeing.
We had originally designed the trial where patients will be enrolled based on being.
Overexpressing FGF are to be on their tumors.
And then as a proxy for that over expression. We had added ctdna because we were concerned that biopsies might miss.
Ms patients and and what we're finding is that we are capturing more patients than we actually thought based on just the over expression alone and again based on the mechanism of action of this drug that it requires protein on the surface of the cell. This is what we would want to see so.
But it is different than the patient population that we saw on our late line phase one study.
I would just add that the way that the sites that come on in terms of the country and site activation is sort of an east to west patterns of the first sites were opened in China and South Korea.
Later in North America.
And most recently in Europe , and so now we're up to 18 countries and sites open and as noted today that most reason is Japan, so whereas in the early days of the trial most of the patients would have been coming from South Korea and China.
Thats now skewing downward as we get more patients entering from North America, and Europe is now contributing a number of patients.
That ratio is going to continue to change as more European patients come into the trial, but as we said this positivity rate is holding at over 30% and seems to be relatively consistent around the globe.
Okay. Thank you and I guess, we do have a quick quick question on BT 155.
So in terms of that type of data presentation W habits at sea.
I think for the 850, you talked about presenting say safety data will then obviously also included some efficacy that is that kind of the format, we should expect that city.
Thank you.
No because we were farther along with dose escalation and with a few hundred 50 at the time of the as ASCO presentation.
We're still in the midst of dose escalation as I noted earlier today on the call.
We're in the fixed dose level.
But it's our plan to present, whatever safety and pharmacokinetic data we have from those early dose levels, but were still continuing dose escalation.
Okay, great. Thank you very much.
We do feel it's important though as Helen noted just given the way that this molecule acts.
By signaling through CD 28.
And acting as a T cell co stimulator.
To show safety and.
Given the history with it.
Monoclonal antibody directed to see 28, which is not safe because it new Super agonism in.
As a result.
Cytokine release syndrome that was very severe we have not seen that at all pre clinically we benchmarked against that very anybody. So we are confident about that going into the clinic, but we also.
Recognize that we need to establish the safe dose in humans and so we think this is a very important.
Set of data for.
De risking this app access.
Thank you.
Our next question comes from the line of Michael Schmidt with Guggenheim Securities. Your line is now open.
Hey, guys. This is Charles you on for Michael Schmidt, Thanks for taking the questions and congrats on the quarter.
Hello.
Let's start off with a couple of clarifying questions on the BMR fight trial on the left you afford to be positivity I was just kind of wondering if you could provide any incremental detail around the percentage of patients that may have tested positive by ctdna alone.
Positive by Ctdna negative by H.C. or positive for both.
Yeah, we haven't shared that publicly yet its.
The ctdna rate of positivity is consistent with our expectations going into the study based on.
And published data and.
What's been team.
Previously.
Thats holding up with whats.
Interesting, though is the IC rate in these previously untreated patients is higher than we expected and that is now.
Holding up as well consistently with many more patients now on study.
Got it Okay and then the next clarifying question for the.
Looks like there was some kind of dose modifications that may have taken place to try to maintain certain levels of plasma concentrations I just wanted to clarify when this modification occurred and how many phase three patients. If any may have received the prior dosing scheme. Thank you.
Yeah, just to be clear wasn't a modification of is that a dosing scheme. We tested in the safety lead in and how I can describe that the dose levels that were tested there and what we took forward into phase three portion, yes. So I can say in our phase axle monotherapy phase one patients were dosed every two weeks and you may recall that we did not have any dose limiting toxicity. So that the dose eventually was chosen based on.
Obviously efficacy being observed in the single agent and then also.
At a dose that we had predicted there be efficacy based on murine models and so.
What we did when we went to our phase three or excuse me our safety lead in of chemotherapy plus the math is we realized what we wanted to do is hit its target target see trough faster and of course, you can do that one of two ways. You can either have a higher loading dose on day, one or you can add a single dose on day eight so that patients are treated every two weeks except for their and their first cycle. They also get one extra dose on day eight so we chose to do this so the latter way demonstrated in that safety lead in that essentially all patients achieved the target trough by day 15, and we think this is important because it's what we saw retrospectively when we looked at our phase one data is only patients achieved that target trough did they actually have.
Efficacy and I think Thats, what Aaron you'd mentioned here on the earnings call that when you actually look at that subgroup.
You have a response rate that's almost 30% again this being retrospective. So so we think it's important to hit the target trough, we think the monotherapy data supports that and every patient.
On the phase three trial from the beginning has received this dosing scheme.
Got it that makes sense and then last question from me shifting gears a bit now to SP, a 150, the b seven each for.
I recall you guys mentioned very briefly earlier on the call that go no go decision may occur in 2020. After you guys finished the safety lead leading.
With the Keytruda SP, a combination just kind of wondering what kind of benchmarks are you thinking about.
Regarding around this a go no go decision and how much efficacy would conclude.
Would you hope to see in order to continue thank you.
Well again I'll start with this I mean as you know these are three tumors with a narrow exception in triple negative breast cancer, but for ovarian endometrial and all the rest of breast cancer. There are no checkpoint inhibitors approved the single agent activity. You know is maybe anecdotally up to sort of 12, 15% or less than that so.
So obviously, we want to see higher the reason I'm a little bit vague because again, it's always a risk benefit and I think one of the properties were seeing about F. 150 is that there is very little toxicity.
So so Dan I don't know if Aaron we really feel like that there's a benchmark I think we've been talking sometimes you ask these questions, saying you'd want to see double what you might expect with the PD one alone.
But again, it's really a it's a whole totality of the data in terms of how well, it's tolerated and and particularly with drugs that have checkpoint activity. You know durability of response is obviously really important as well, it's really more the the overall survival and PFS arguably at times it can be more important than response rate.
Understood. Thanks for the questions and thanks for your time.
Thank you Charles.
Thank you. Our next question comes from the line of Chris Shibutani with Cowen. Your line is now open.
Great. Thank you very much apologies I missed part of the beginning of the call. So hopefully I can.
Raise the topic that hasn't already been addressed if so please do let me now.
Looking to see with regard to your thinking around business development. The overall strategy.
In particular.
You had described continued efforts to explore that how are you feeling about that relative to some of the decisions that you've had to make to sort of narrowing your focus a little bit earlier this year.
What's your outlook.
Yes.
Thanks, Chris for the question for calling in so business development.
He is an ongoing focus of ours, we have discussions ongoing now.
That are active spanning multiple assets, we don't provide guidance on those.
But we do feel that it will be an important part of our strategy going forward as it has been historically as we look to collaborative relationships access non dilutive capital, but also.
Other things as well so that can be.
Broader development programs combination agents for example, global manufacturing and commercial reach.
All of those sorts of things are important elements to us as we seek to advance the programs and five prime so.
It is an active area for us we don't guide on any business development activities.
But it is core to the strategy for.
How we intend to advance these programs and discussions are active.
Great No I've always thought that the proteomics platforms would be valuable asset in terms of figuring out how to further leverage that.
During this year you've also.
Announced previously that your Chief Scientific officer was moving onto another opportunity can you update us on the status of your efforts to recruit someone to replace that important role.
Yes, so we have hired a search firm retained search from there.
Efforts are ongoing that they have identified a number of interesting candidates.
But in the meantime, we have assigned the duties of the former Chief Scientific officer to two very capable.
Vice President here at five prime so.
Each has responsibility for.
The half of the research organization.
One group focused on discovery in the late stage research programs. The other focused on our biotherapeutics and molecular biology areas.
And so they have risen to the task nicely and none of the programs have.
Really suffered as a result of the departure and they are still progressing.
As we had hoped but.
Search is ongoing and we'll update you further.
Great and then you provided some updates on from.
Shifting of the components of your board members can you just help us understand what you're thinking about in terms of those decisions that you've made in terms of what the relative distribution of capabilities or insights that you are hoping to gain at this stage for the company.
Sure, Yes, we strive to have a board that is composed of.
People with diverse backgrounds experiences and capabilities and I think if you take note of the two recent additions.
What you see there is weve added.
In the case of Carroll's Shaffer.
Who was most recently at Wells Fargo in equity capital markets somebody who's a very experience.
Person with respect to.
Capital markets and financing biotech companies. He has also been an operational role at lexicon pharmaceuticals, and enter pass and so she brings a lot of depth in terms of financial acumen.
Awareness of.
Capital markets and has worked with a number of companies like ours and getting them finance capitalized.
So that was the rationale for adding Carol Schaefer and then we're also happy to welcome Lori Lyons Williams.
She brings a different profile she is a.
Commercial leader and is currently in that capacity at their Mira.
In the dermatology space, and Allergan before that and others other companies as well but.
Very experienced and capable commercial leader, who is launched important brands built out commercial groups and I think.
Brings real depth and current acumen about how drugs are.
Brought to market commercialized reimburse so.
That's why we have chosen to add those two members to our board I think.
With those additions, we have a well rounded and diverse board.
And they were really intentionally selected just given their backgrounds and capabilities.
Great and then one last one and I'll try to laser down to one of your assets. It is a partnered asset but the Tim three I noticed in the release you mentioned that the expected trial sizes increased from 330 to 383, what should we take that to mean and apologies again, if you've already about that.
No that's fine we just mentioned it briefly and.
It's Uh huh.
A significant program, it's a phase one two trial and it has multiple components. So initially there was a dose escalation with.
Monotherapy anti Tim three.
And then BMS is combining both with.
Vivo as was recombinant hyaluronidase for potential Subcu administration.
You know I think it signifies continued investment in this program. We are pleased with BMS is doing.
With the Tim three asset and we can't obviously divulge anything confidential about the nature of the trial.
So I'll have to leave it at that but.
We're pleased with their commitment to this program.
Great. Thank you for the responses.
Thanks, a lot Chris.
Thank you. Our next question comes from the line of Tony Butler with Roth Capital Partners. Your line is now open.
Thanks, very much Helena rare and just.
Apologies for sticking with a free trial with just three really brief questions.
When you have a conversation with the sites or how are you.
I guess the question is how did you communicate to them.
But you wouldn't have that interim pause.
And which will be around the fourth quarter and the reason I asked this is because this is actually question too.
You were asked about the hazard ratio on this call, but I didnt recall for that.
You were going to put the futility you wanted to put the futility analysis hurdle.
Having as a ratio clearly less than a one so there would be clearly some activity and I want to know if that's still the case, because importantly would you communicate what that number is back to those sites. Once that analysis has occurred importantly, because you alluded to also to their excitement to reenroll and I wondered if they may go hand in hand, and then the last question is.
You May have said this forgive me.
For missing it but.
His enrollment and ramping at all sites not just the ones that you would previously enrolled but also with the newer sites, which just opened thanks a lot.
Thanks, Tony.
Ill start and then Erinle I'll jump in with the things I forget so first in terms of the communication. The pause we are in the process of doing that that needs to be done in conjunction with lumber going public with you said the investigators wont hear about that tell over the next 24 hours.
We obviously didn't communicate to them about the.
About the findings in terms of the prevalence of FGF are to be and so thats, probably and as we think thats contributed to the fast enrollment in the enthusiasm of the study.
In terms of that hazard ratio, you're absolutely correct and I think that is still our intent is to have a hazard ratio of less than one.
I remind you that when you're looking at futility, what you're doing is you're looking at the ability of your trial to demonstrate the benefit of the drop you're not looking at at the drugs benefit per se. So so.
Futility the actual bar is usually not something that's communicated publicly.
What is communicated obviously is.
After our discussion with the DMC is that we have passed futility and that the trial is appropriately sized and designed to demonstrate the benefit that we think we need to get approval of the drug. So obviously now the investigators do here outcomes of BMC. They will hear that the utility has been passed but they will not know what that bar is.
And then finally I guess was a question about enrollment. So yes, we have not seen you know greater interest or less interest anywhere I think as Aaron said earlier and I thought that was very nice he said that.
We've opened sites going from east to West and that's just more a regulatory how long it takes to open trials in various countries, but whenever sites have opened their enrolling at approximately the same rate China, obviously has more gastric cancer, there, but higher proportionately for there yes.
Patients enrolled per site, but otherwise, it's not really a geographic difference in terms of.
Enrollment.
Oh, thanks very much thanks.
Thank you Tony.
Thank you. Our next question comes from the line of Salveen.
Right there with Goldman Sachs. Your line is now open.
Yes, hi, Thank you for taking our question different Mariana Brightman off on patrol Dean.
I had a couple on.
The FCC once you start it's in one of her the right now, but it looks like combination will make sense.
Are you thinking about combinations going forward and what this will be an ulcer, which indication.
So for 155 for the F. The CD HDFC protein is that which is what led to the beat no need for anybody.
So one final five certainly preclinical data suggest that that a combination I think we presented data at HCR.
Last year.
And and there is excellent preclinical data to suggest that a combination may work better than the single agent right now we're concentrating on the single agent and so as we said we think it's really important to show that Theres a therapeutic window here for this particular mechanism of action.
But we certainly are keeping the idea of a combination in mind.
Got it but do you have any idea what the indications like.
Right now with the basket trial, but like what are you thinking or are you just want to see what the data shows.
We've had lots of conversations about this I mean, I think as we do a dose escalation to some extent it will depend what we see in the mechanism of action, obviously, what we're hoping to do is to see a much broader.
Response in then what you see with the CLA agonist alone for example, because because we're doing we're inhibiting that mechanism as well as directly stimulating the T cells, but at the same time, obviously, it's you have to have T cells. There. So we do have some thoughts about this that we have not made those public.
Got it got it.
The other one I just wanted to.
Just some commentary on.
We're still has expanded the computer program it looks like they keep bringing new indications.
I was just wondering what is the dialogue about that.
What do you hear from them like why.
What do they see that they keep bringing more.
Indication, but yes, I mean I.
Yeah, our team as you know, we well our teams do work some together again be a massive developing the drug now, but but I think we're really pleased by the amount of resources that they're putting towards it the number of trials the broad indications that they're looking at and unfortunately, I can't say more than that other than it's clear that that BMS is not winding down their effort there.
To the contrary so.
Yes.
Thank you thanks for taking the question.
Thanks Mariana.
Thank you. Our next question comes from the line of Eric Joseph J.P. Morgan. Your line is now open.
For taking the questions I just wanted to clarify on the futility analysis like that.
And it's based strictly on the primary endpoint of overall survival or whether we get the opportunity to look at.
Some of the secondary.
Endpoint of PFS your objective response rates and.
I guess secondarily I guess, given the surprising that proportion of high Expressers for FG, if our to be and the you know the obvious implications is that as lasik prognostic indicator.
Is there any reason to think that if your TV would function differently as a therapeutic target our line of therapy. Thanks.
Yes. So I think these questions is the second one so no. There's absolutely no reason to think that it would be by line of therapy I mean.
Yeah, they are clear growth factors that stimulate.
The cell to divide and so it's going to be blocking that growth factor and then the second mechanism of the ADCC, that's going to be regardless of line of therapy.
In terms of the futility again as he said we have a proposal lever that we'll be talking about with our DMC. So we haven't said specifically what will what endpoints will be using or whether it will be a composite.
Got it thanks.
And maybe just a strategy clarification question as it relates to 150 is the expectation at this point.
Yeah the monotherapy.
Program will not be advanced and really going to just go no go decision will be based on the data that you're seeing in combination with keytruda. Thanks.
So now I'm really glad you asked that question. So that's absolutely not the case I think what happened is to US we were really excited ASKO because what we felt that the debt. The data represented was just how much.
How enthusiastic and the investigators were how easy it was to find these patients how safe the drug was.
Our goal at ESMO is some of those same things now that we're going to have approximately he said 30 patients who have been dosed dosed at the full dose of 20 milligrams.
Yes.
Per kilogram.
And and again some early early sense of the efficacy now I think we are trying to temper expectations in that we do not.
Expect based on the mechanism of action and our preclinical data that this is something where you're going to see 70% response rate. We do not expect that we expect what you might see and Thats why we use those analogies of like herceptin alone or something where htert drugs.
Our projected that our very successful drugs have some single agent activity, but really their greatest benefit has been in combination and because of the ubiquitous nature of this be seven H for over expression its homogeneity.
Its lack of expression on normal cells that lack of us seeing toxicity that that is very likely where we'll end up developing this drug is it also allows you to move earlier lines of therapy.
So so you should expect to see some single agent something now, but I think what we're trying to do is just make sure don't go out there thinking it's going to be a 70% response.
Yes, and tried to stay consistent about this point as we've talked about this program since they went into the clinic, which is.
We do want to see single agent activity were demanding that does not mean, the ultimate use will be as a single agent.
Herceptin.
It's combined with the chemotherapy, we think that's again, an analogous set up here.
So.
We are not saying no to monotherapy activity and we are also saying that we think the more likely.
Maximization of patient benefit will be in combination.
Got it that's very helpful I guess.
Maybe just and setting the stage for ESMO a bit more here can you just talk about sort of.
The distribution of those 30 patients across.
The different histology cohorts that you're accruing here across breast ovarian and to be true and the material and sort of.
How to think about duration of follow up.
As well thanks.
Well I think as you're saying that we've rolled about what we'll have data on about 30 patients will have had one scan. So again, it's going to be early right.
And NFL a handful of had.
Then on long enough to have had a second scan I'm in terms of the distribution well you can imagine breast and ovarian is little more common than endometrial. So.
Is that more both in there arent material, but it's not a huge difference between the different arms.
Great. Thanks for taking the questions guys appreciate it.
Thanks, let Eric.
Thank you, ladies and gentlemen, as a reminder, if you would like to ask a question. Please press Star then one on your touched on telephone.
Our next question comes from the line of Jim Birchenough with Wells Fargo. Your line is now open.
Good afternoon, and nickel, but Jim Thank you for taking my questions.
I was just going back to.
Bema trial.
Since you made this discovery of the I'd see posted double positive patients.
Have you screen the literature to look for.
Instances, where this has occurred the targets and what's your theory on why this is occurring in these frontline patients but not the.
Chemotherapy treated patients and then.
Secondarily, just a futility allow full analysis of both a double positive and the single positive patients and then I have a follow on thank you.
So I think the first question really is.
In some ways has to do with the assay and then you have to recall that we are the first.
Company to have.
Drug that is geared to FGF are to be over expression. There are drugs out there oral tyrosine kinase inhibitors for ft. If our two mutation, but that's completely different so one of the difficulties with looking at the literature as we're the first people to work with Ventana to come up with.
A high quality audio assay so.
If you come to the literature, you will find variations and over expression, depending on what assay, they're using from I don't know a low of say, 7% up to 60% to 80% probably those 60% to 80% is because the assay is probably not very good.
So.
So even our 30% that was falling into what you might see out there if you hunt around.
In terms.
Your second question, which has to do with the.
Kelly.
So so again.
Futility is is again really something that that we are choosing to do right, which is why it's not you don't have to pre specified that an a protocol because again, what we're trying to do is to make sure the trials designed appropriately.
Certainly the DMC will have the information about patients whether there I see positive ctdna positive or both.
But but again, we havent disclosed how we're going to ask them to look at that so.
Yes, but our.
I'm being reminded but our our goal again is for that.
On purpose of the trial that because the inclusion criteria are either one ctdna or I.H.C. that that would still be.
B how this trial is designed right now so.
But you are speaking to whether or not.
The outcome of the utility could be some change in the in the trial design or size yes.
Yes and no.
Thank you and their earlier question.
Yes on literature data Weve.
Dug into the findings from the toga trial.
Which again is the phase three study of Herceptin, plus chemo versus placebo plus chemo.
And there you can see that it was over expression that predicted the survival benefit from herceptin not gene application. So.
In patients that were lower.
They were lower Expressers, there was no benefit so there I see one for instance.
There was no.
Hazard ratio benefit seen even if their gene amplified.
But in the patients who were I see two or three status.
Whether or not they were amplified in this case basis.
There was a significant benefit in the hazard ratio was 0.6, but again, we think that's irrelevant analog and makes lot of sense for an antibody that works on the cell surface and blocks growth factors and engages NK cells.
It shouldn't matter so much whether there's multiple copies of the gene as long as the target is there and you can prevent the good growth vector signal in the.
Engage NK cells, so that seems to be what happened with.
Herceptin and the target trial.
We think thats instructive and germane for the fight trial as well.
That's very helpful. Thanks.
Sure and then move into Q1 50.
The patient characteristics of these expansion patient that was hit ESMO.
The difference in up from those are enrolled in the dose escalation in the biomarker positive patients and I fully acknowledge that the doses that you were testing in those patients.
Below the 20 milligrams that we should expect that data to be different data from ASCO.
So you're right. The main difference is going to be the dose. We now again ASKO had a proportion of patients who are b seven eights were positive at a proportion that were negative and only a couple that had.
That we're in a dose level you might have expected to see something for B 784 positive. So.
I think this is going to be a a larger number.
Patients, obviously 30, but again early.
So I think you know the hardest thing is going to be how do you judge patients who have stable disease. When they believe one scan right is it going to be.
Stable disease on your way to a PR or stable disease on your way to progressive disease, Yeah, it'd be too early for those patients right.
Okay, but but stable disease.
Hey.
Hi, getting some benefits one of the themes.
Doug Hello.
Right yes.
And then can you remind me of the roughly how many patients you want to enroll in each of these cold weather are employing assigned two stage design.
Yes, we have a Simon two stage design, so and up to 30 is how the cohorts are written right now.
Okay.
And then the last one for me on 150.
I mean, given the nature of this target I'm, assuming that the the dose that you had to settle that was.
Very much below a therapeutic dose you.
Clinical six now how many dose levels have you planned or maybe another way to ask the question is when do you get to a dose level with a foam academics.
You will see is it similar to what you needed to see in preclinical models.
Yes, I mean that you know obviously, we you you have to have that to go into the clinic right and that is a big discussion you have with regulatory agencies, because that determines to some extent where you start so.
And I realize I'm I'm I'm avoiding answer your question because we haven't made that public so we're getting close.
Maybe where they're going to close either in a little while.
Yes.
Fair enough.
Hey, look lets say youre as Mike. Thank you very much.
All right. Thank you Nick.
Thank you.
This concludes today's question and answer session I would now like to turn the call back to Aaron.
Her for closing remarks.
Thanks, as I said at the beginning of the call all of our clinical programs are on track and just to restate. The near term priorities. Those are one the merit to them and the fight trial.
To advancing the most promising F 150 opportunities.
Three safety and dose finding for SPT one fivefive.
And as I mentioned, we're committed to making data driven decisions.
And also exercising tight fiscal discipline.
We've got the resources to act on data from the Phase futility analysis, when 50 studies and the ongoing trial of SPT 155 and beyond.
So with that I'd like to thank you all for joining US today I'd also like to thank the patients and investigators participating in our clinical trials are five prime employees and our strategic collaborators who all contribute to the continued advancement of our programs. Thank you very much.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude todays program. You may all disconnect everyone have a great day.