Q1 2021 Constellation Pharmaceuticals Inc Earnings Call
Good day, and thank you for standing by and welcome to the constellation Pharmaceuticals first quarter 2021 earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During this session is on each press star one on your telephone.
On this.
Please be advised that today's conference is being recorded if you require any further assistance. Please press star zero I would now like to hand, the conference on would you speak your day Tier, California, Vice President of Investor Relations and Communications. Please go ahead.
Uh huh.
Yeah.
Yes.
Thank you operator.
He has got constellation's first quarter 2021 financial results and I'll finish up on it.
Please turn to slide two.
Before we begin I want to point out that our presentation. Today will include forward looking statements, which are subject to check them out.
Actual results may differ materially due to various important factors, including those described in the risk factors section as well as discussions on potential risks uncertainties and other important factors in the company's most recent filings with the Securities and Exchange Commission Inc.
The company's quarterly report on form 10-Q for the first quarter ended March 31st 2021. Please.
Please turn to slide three.
This morning, we are joined on the call I kick off I thought that I Chief Executive Officer.
Doctor, Jeff Humphrey I, Chief Medical Officer, who will update you on our clinical program.
And I was a chief financial Officer, who will review our financials.
We will also be joined by Doctor Patrick Toya I cheap.
Scientific officer for the Q&A question on the call sheet.
Please turn to slide four.
And now I will turn the call over to Jr.
Thank you Tia and good morning, everyone.
Constellation is poised to transition from a development focused organization to a fully integrated commercial stage biopharmaceutical company.
Our lead asset <unk> is currently in a global phase III pivotal trial and enrollment is now underway.
Our goal is to transform the standard of care for these patients and to make <unk> the backbone of the net therapy.
In addition, we have opened a new cohort in the phase two trial to evaluate <unk> in a central thrombocythemia, where.
We're exploring opportunities to evaluate additional indications.
We believe that a broad development program could position <unk> as a cornerstone hematology product in future.
We also intend to demonstrate best in class potential for CPI <unk> are easy each two inhibitor, which people eat me a broad therapeutic potential in a number of cancer indications.
Please turn to slide five.
Turning your attention to our pipeline labor standards in the phase III program in myelofibrosis.
The focus of that program, it's first line JAK inhibitor naive patients with.
We recently completed the dose escalation portion of our phase one two trial of <unk> nine and we are advancing this program to the phase two portion of the phase two proof of concept portion, which Jeff will tell you about shortly.
We anticipate presenting results from the phase one portion of this study at <unk>.
Our next program is C. P. I 42, which we believe is the mechanism that could impact on myeloid biology.
Brand our footprint in hematologic malignancies.
This program is in IND, enabling studies.
Our discovery efforts are aimed at continuing to identify novel mechanisms to drive additional growth for the company.
Please turn to slide six.
We believe that <unk> has the differentiated profile necessary to potentially become a foundational therapy.
Well then in myelofibrosis landscape that is rapidly evolving <unk> is a first in class oral bet inhibitor that could provide hematologists with a new mechanism of action and it has the potential to realize disease modifying treatment effects beyond symptom control.
More importantly, a growing body of data and clinical experience with this product candidate show preliminary evidence of efficacy and Tolerability, both as a single agent and in combination with rux a litany.
Moving to slide seven.
Palaver said is the first agent to show proof of concept in combination with rux silicon it in the first line setting of myelofibrosis.
This slide summarizes our clinical and translational data presented at Ash, which reviewed very positively positively by our investigators and the M. P on community.
The waterfall plot shows that 67 per sub on patients receiving <unk> plus rux letting it achieved and lets see on 35 response at 24 weeks, which is roughly twice the rate of rux slipped them alone.
Well controls.
And we saw a higher rate and deeper symptom response compared to controls from upselling of involved as well.
The Spider plot shows at spleen reductions with deep and durable in individual patients.
These data support our vision to transform the standard of care for myelofibrosis.
We believe the translational data are particularly exciting with more than 100 matched pairs of pre post treatment bone marrow biopsies approximately one third of MF patients receiving black collaboratively across our first and second line treatment arms have shown improvement in bone marrow fibrosis, mostly within six months.
Very few patients showed worsening fibrosis.
Even more importantly, the bone marrow biopsies from most of the JAK inhibitor naive patients showed trends towards normalization and the number in distribution of megakaryocyte and red blood cell precursors.
Vivo studies from MF patients further supported this finding.
And do you think vivo studies Polaris that normalized maybe curious on differentiation and promoted red blood cell maturation.
And finally, the changes in bone marrow may result in improved hemoglobin levels the.
The increase in mean hemoglobin was greater in patients with collaborative alone then with collaborative combined Brooks litany as expected.
The largest increase was seen in patients who are anemic at baseline.
As shown by the Orange lines <unk>.
<unk> was generally well tolerated.
All of these preliminary data were highlighted at ash in December and support the belief that <unk> may be disease modifying.
We're excited to take next steps with this program. Please.
Please turn to slide eight.
We estimate that in the U S and Europe. There are about 30 to 35000 patients prevalent with myelofibrosis, reclassify that intermediate or high risk.
Of that group roughly half from currently receives rux Lytton of therapy.
Those many experience suboptimal response with a relatively short treatment duration.
In the near term, we believe that the addition of <unk> therapy may not only expand the number of patients who can benefit from treatment, but also offer the potential for longer treatment duration through more durable responses.
Over the long term, we believe that we can further develop <unk> into a backbone of myelofibrosis therapy with the potential to shift the treatment paradigm for this debilitating disease.
With that I will turn the call over to our Chief Medical Officer, Jeff Humphrey to share with you updates on our clinical programs.
Thank you Jacob.
Turn to slide nine.
Trial sites from manifest to have been initiated in both the U S into Europe and dosing is underway in the phase III manifest trial of collaboration we've received health Authority and Ethics Committee approvals in many countries. We're pleased with the level of investigator interest in trial and we've already brought on board some of the larger academic centers.
We have however seen some impact from COVID-19 on site initiation of certain clinical sites have experienced staffing shortages trialed backlogs COVID-19 trial prioritization and overall country Lockdowns.
We expect to have more visibility on manifest to execution over the next several months and we expect to provide a further update in the third quarter as more sites come on line.
Regarding Gina toxicity related efforts I'm pleased to say that study reports, including the most recent study reports we mentioned on our last earnings call have now been submitted to F. T. A without further comment from the agency to date.
We have updated our investigator's brochure and informed consent to reflect these findings in patients and investigators have been notified we do not expect any impact from the updated assay results on the conduct of manifest too.
Turning to the phase two study we expect additional analysis from manifest trial to be presented at the European Hematology Association or <unk> heart based on on September 29th day to cut focusing on translational data. We continue to be very excited about the effects. We are seeing on from there.
With fibrosis, and we will be presenting centrally reviewed data for the first time.
We've also assessed cytokine levels at baseline.
Fine level changes during palaver said treatment.
Pharmacodynamic assessments and extensive baseline mutational analysis. In addition, we will also present two other posters. The first poster will assess splenic response by subgroups from on three of manifest on the second poster will present, the anemia response seen in patients from arms, one and two mcmanus.
Yes.
Moving on to our easy H two program, please turn to slide 10.
We designed our C. P I O to O nine to improve on first generation easy H two inhibitors in a number of ways, including increased potency long residence time on target and absence of audio induction of metabolism to maintain exposure levels over time.
As discussed on our last earnings call with these improvements C. P. I O to O nine may extract an enhanced therapeutic potential of E Z H two biology.
Please turn to slide 11.
We recently completed the phase one portion of our phase one two study of C. P. I have two on line for patients with advanced hematologic and solid tumors.
We observed improvements in the pharmacokinetics and pharmacodynamics of CPI of two nine by historical comparison to first generation <unk> inhibitors.
Unlike multiple first generation molecules based on the phase one data to date, the PK profile indicated no evidence of audio induction of metabolism.
In addition, we observed comprehensive target engagement as measured by multiple Pharmacodynamic markers.
And an improved P D profile that supports once daily dosing.
For example, please see the right hand panel that shows the gene expression profiling data from the first four dose cohorts from the phase one portion of the trial.
This heat map shows easy H, two target gene expression at different dose levels.
Low gene expression as indicated in blue and hygiene expression as indicated and read it.
It is encouraging to see that the magnitude of gene induction increases with increasing doses of C. P. I O to O night.
We believe that the C. P I O to O nine related modulation of gene expression is consistent with our hypothesis for this compound to have best in class potential.
Additional P D data will be presented in our upcoming <unk> presentation.
We established a once daily oral dose of 350 milligrams as the recommended phase two dose.
The safety profile of C. P. I O to O nine was in line with expectations and manageable, we will share with you additional details from the phase one portion of the study.
Pete.
The poster at <unk>.
Moving on to slide 12.
For the phase II portion of the study we plan on evaluating the anti tumor activity of C. P. I had two on line monotherapy in cohorts of the following tumor types.
Lapsed urothelium carcinoma, relapsed ovarian clear cell carcinoma, and relapsed endometrial carcinoma, all with known arid wanting a mutation.
And relapsed or refractory lymphomas.
These cohorts are open for enrollment and we have dosed the first patient.
We're planning on enrolling up to 29 patients per cohort.
As part of our future development plans, we plan to add patient cohorts of malignant mesothelioma with known Bap one loss.
Have progressed on one prior line of therapy.
<unk> metastatic castration resistant prostate cancer, who have progressed on at least one androgen receptor signaling inhibitor at last at least one taxane based therapy.
The goal of the expansion cohorts to further evaluate the safety and anti tumor activity of CPI at two O nine monotherapy with a tumor types in the world.
And now I will turn the call over to Emma.
I think just moving on to the financials on slide 13, we had a net loss of $40 $1 million or 84 cents per share in the first quarter of 2021 in line with our expectation.
Our cash cash equivalents in marketable securities at the end of the first quarter totaled $382 $1 million.
Efficient, we believe to fund our operations into mid 2023.
We plan to use these resources to from manifest to the phase III clinical trial for collaborative and to start building the commercial organization needed to launch the product candidate.
As well as to explore the utility of coli proceeds and other indications.
In addition, we believe we have sufficient funds to complete the phase one two clinical trial for CPI on two or nine.
Well as to progress on discovery and preclinical pipeline of compounds and from general corporate operations.
Moving on now to slide 14, which shows our corporate milestones for 2021.
Overall, we're pleased with the position we're in for the remainder of this year, we expect to share with you.
Data from our phase two clinical trial manifest with a translational update in the midyear time frame at Ehealth on a clinical update by the end of the year.
We also aim to provide an update on potential new indications by the end of the year.
The CPI O to O nine we plan to provide an update from the phase one portion of the study by midyear that go on.
And as Jeff announced earlier now that we've opened up the phase two expansion cohorts, we expect to provide an update from those cohorts by the end of the year.
That concludes our prepared remarks for this morning, So I'll turn things back over to the off price yeah.
Operator could you. Please open the line for questions.
Thank you as a reminder to ask a question you need to press star one on your telephone to withdraw your question press the pound key.
Our first question comes from Brian Abrahams with RBC capital markets. Your line is open.
A bit more on what you observed what you're observing clinically with O to O nine I guess, how the biology, the PK PD and the efficacy and safety of guided your choice of recommended phase two dose in the populations that youre going.
Into and how what you're observing differs from what you saw with 12 five.
Hey, Hey, Brian This is jigger I missed the first half of your question could you repeat it.
Yeah, absolutely just wondering if you could elaborate a little bit more on on what you've observed clinically with O to O nine I'm just sort of curious how.
The biology of the PK PD, the efficacy and safety that Youre observing is guiding.
Dose selection and choice of populations to go into for the Phase two portion and then how 'bout youre seeing may differ from 12 O five clinically.
Yeah, Yeah, just you know we will be presenting the full dataset at <unk>, but.
But maybe Jeff can give you a little bit of color.
Yeah, Hi, Brian This is Jeff Humphrey, So four O to O nine the phase one portion as you know is about PK safety and we did this study with pharmacodynamics and saw really what I would consider to be a dramatic dose gene expression response.
<unk> not seen with CPI 12, O'five that certainly does help guide our selection of recommended phase II dose. However recommended phase two doses typically chosen based upon safety findings and we did have toxicity results on them.
Not unexpected that guided on a selection of recommended phase two dose and as Jager said, we don't want to run the we don't want to front run the <unk> abstract we worked hard on the ESCO poster and you'll find a lot of information there.
Maybe if I can just add to that I think as we as we embarked on on discovering and developing O to O nine.
We had a vision in mind, which is to really induce a step change difference in the level of target engagement and we've shown ample data pre clinically.
Debt that we can induce those those levels of comprehensive changes and target engagement.
With you the H two with with O to O nine.
And I think now with the with the clinical profile that we have we feel very comfortable that we're able to replicate that that type of step change in target engagement relative to a first generation <unk> inhibitors, including 12 O'five.
Got it that's really helpful look forward to that presentation, and then maybe one more from me if I if I could with.
With respect to the ongoing manifest two phase III study congrats on getting that underway. Just wondering if you could talk about maybe the latest on your reached the mechanism for potential resizing of that study based on spleen and TSS, what what your powering assumptions were there and just given the COVID-19 headwinds to site initiation, whether you expect that.
Could potentially still be by the end of this year early next year, how we should be thinking about potential disclosure of.
On upsizing of the study.
So let me make a couple of comments and then I'll turn it over to trigger but.
The powering assumptions are based on the response data we saw on manifest in the historical data of Fracs from simplify one we will power. The study to have the best chance of success and we will provide additional data later on in the year.
Yes.
I think as you mentioned, there's a mechanism for resizing of the study.
And.
Again.
Those would be details that we would provide later in the year.
Okay understood thanks very much.
Yes.
Yes.
Thank you. Our next question comes from Marc Frahm with Cowen and company. Your line is open.
Hi, Thanks for taking my questions.
Congrats on progress.
One quick one following up on Brian's question.
You mentioned that the recommended phase two dose was selected based on.
<unk> words or can you just say what those were and then.
Follow up on on.
Colebreath on program Yeah, no. Thank you for the question, but we'd really prefer that you see the <unk> presentation, which is only a short while away so that'll.
That'll be coming again.
On the safety profile is manageable for CPI <unk> hundred nine at the dose selected.
Okay, maybe just add Inc.
Nothing unexpected based on kind of what you've seen from our preclinical work or or work from other usage to exhibitors.
Correct Okay.
And then maybe Jeff just on progressive.
B E T expansion cohort can you give an update there where enrollment is in plants.
Plans to disclose data later this year.
How dependent do you expect that data set to be or is it really going to be are still very much work in progress.
Yeah. Thank you so the that the amendment to manifest as open for arm for <unk> and <unk>.
And again.
It will these are patients that are not frequent in the community and we will be providing an update on enrollment later in the year. So the trial's open for enrollment of E. T. Now.
Yeah, I think I think previously in the past Marc you said that.
It wouldn't be the full kind of cohort of patients, but it's possible that we would have.
Data from a handful.
Later in the year, and we're still working hard towards that.
You have noted one of the things that we were looking to learn about this is kind of the the frequency of presentation of these patients and.
Well certainly as we as we've worked through this cohort of patients will have a good view on that.
Okay. Thank you.
Thank you our next question comes from.
Dave our condo with true Securities. Your line is open.
Hey, guys. Thank you so much for taking my question regarding the data to be presented at <unk> can you talk a little bit more about what do we expect especially in in the abstract.
And should.
Should we expect an investor event at <unk> like you hosted last year and then one follow up question on O to O nine mm. In addition to the yard one <unk> mutant solid tumors do you also plan to initiate trials he said in mesothelioma and in.
On lymphoma, just to get a had a little debt can you talk a little bit about the total opportunity you're looking at from the average one ear on the BOP one mutants.
Patients I know, it's maybe a little too early to talk about it but.
How are you thinking about.
Receding like is it.
Tumor agnostic Orange money once you see these patients in these three indications that you're initiating your trials Inc. Thank you.
Yeah. Thank you so the data at <unk>, just mentioned is really around dose related and this reduction in inflammatory cytokines on the reduction in bone marrow fibrosis, there's a cohort of paired bone marrow biopsies that have been centrally reviewed that will.
Data will be presented as well.
And there will be data that talk about the responses regardless of mutational status. So I think those are in terms of <unk> said those are some of the very important presentations as well as the effective collaborative on anemia in patients under treatment.
When it comes to the planned cohorts in mesothelioma and lymphoma.
As you mentioned, we are very interested in <unk> and in Bap, one Arab money is really about the solid tumors.
We mentioned the endometrial urothelium.
On.
Cohorts that I mentioned and.
In terms of the size of the opportunity. So on these as helium is a fairly uncommon tumor I think roughly around 3000 patients in the seer database.
In the U S.
We're looking at that one, but we'll be looking at at that one launch, but we'll be looking at wild type as well.
But with an initial focus on that point I think for.
You were focusing both on on knees are feeling them in lymphoma. I think there are cohorts are designed as two stage enrollment and we're looking at enrolling up to 29 patients and based on the observed response rate.
We will design our development plan from there.
If I could just add a couple of quick a couple of comments.
Uh huh.
I think we will what we laid out is.
Really I mean, the intense focus will be for us to start the drumbeat on on.
On kind of defining what disease modification means.
And it'll be the first of kind of a building dataset.
Patrick and his team had been had been generating some of that data over the past year or two.
We're working on further further deepening into the some of the types of analyses that we've done but also taking them to the next level and we will see more of that likely at ash and beyond.
But we'd like to have is that by the time that that phase III data on hand that there is a really good understanding of some of the disease modifying mechanisms in the data that we see from the the collaborative studies really becomes synonymous with with disease modification and so that's kind of a it's kind of an early step in that in that in building that drumbeat.
And then shifting just to your your your questions are on Oh, 209, and kind of size of the opportunity. It's a good question. It is a little early.
You know as you can see from the approach that we're taking we really set up our for ourselves a broad development plan that gives us a lot of optionality.
On where to go where following the science at.
At this point.
We think there's a lot of good rationale around the debt genomic features that we've chosen as well as some of the following some of the day to that had been presented with other easy H two programs and in total should lead to a very significant commercial opportunity, but it's a little early for us to kind of more precisely define that today.
Alright, thank you so much.
Thank you. Our next question comes from whole Chen with Jefferies.
Your line is open.
Hey, guys. This is how calling inc. For Kenny sheet on thanks for taking my question. So maybe just a follow up.
It could be earlier, but what percentage of patients having on <unk> mutations on maybe vap, one mutations across the indications based on them on your study.
Thank you actually yes, it depends on on the indication itself I think I think we've talked about this in the past where.
There are certain tumor types.
Bladder cancer, where you know roughly a quarter of patients have have everyone mutations.
There are other tumors, where we're close to half of them.
Everybody mutations, but there, but theyre smaller patient populations to begin with.
One loss in particular is highly prevalent in mesothelioma.
You know in terms of.
Certain types of music on me that we're targeting more than more than half of the patients would have that one back on lost mutations.
Thank you very much.
Thank you. Our next question comes from do Kim with BMO capital markets. Your line is open.
Hi, good morning, Thanks for taking my questions.
First on two O nine do you still have a plan to combine two and on with the standards of care in solid tumors and do a dose escalation phase one and.
What what is exactly the timing of when you initiate the cohorts of mesothelioma and prostate cancer.
Thanks, Joe.
I think it is very reasonable for us to try to combine O to O nine with standard of care.
Where I think we would like to kind of sequence that step is to first generate.
Very compelling single agent activity.
And then and then be ready to then quickly move into combination studies, but so we have taken the step to gain some of that combo work.
Until we see some some of the single agent activity that we're looking to see from these cohorts, where the biology is quite strong and with a molecule like <unk> hundred nine we would expect to see it.
And sorry can you repeat your second question yeah.
On the cohorts of mesothelioma in prostate cancer will start you said you are planning on initiating those cohort.
Yeah, I think we're not ready to comment on the exact start time for those cohorts.
Those were certainly things that that we brought into view into our own planning a little later than the average one in lymphoma activities and so.
But we'll certainly be able to provide an update on that in the near future.
Got it thank you.
Question on manifest true you said that COVID-19 had is impacting enrollments and.
Just wanted to know if that changes your expectations for when.
We will get data for that trial or is there an opportunity to.
Regain.
On the speed and that enrollment rate by the addition of.
Active sites.
Yeah. Thanks for the question I mean, the impact of COVID-19, It's inescapable and we're managing through it the best we can and we're on the motive site start up and site activation most of our clinical trials are and Ah trial sites are in areas that are affected by COVID-19, eight and as he mentioned we are experiencing delays in clinic.
Trial site initiation those delays include.
I am very commonly disruptions at the site included limited Resourcing and staffing.
However, the enthusiasm for <unk> from both the physician community and from patients is high based on E. Mails that we're receiving for trial participation.
We're working very closely with our CRO in order to address issue, we have our field Medical Affairs force that is finding additional sites for participation.
And they are actively strengthening relationships with physicians physicians and finding finding new sites. So.
I think we can provide more information at a later time, but right where we are strongly initiating the study at this time, but if it's okay. If I just add debt.
I'll comment I think I think it's a little early for us to comment really on enrollment for per Se I think Jeff just mentioned that the.
The impact that we've seen has really been on site startup.
And yes, I think as the pandemic resolves our hope is that there is sort of.
On a pent up demand that then kind of picks up it but its really early for us to to really comment on enrollment trajectory specifically until the the sites that debt that we anticipate having having up and running are up and running and we're seeing the rate of patient enrollment in those sites and so.
Overall no change at this point in and kind of what we have previously messaged on this point.
And we'll certainly keep a close eye on it over the coming months and provide an update as well.
Great. Thanks for the detail.
Thank you. Our next question comes from Ren Benjamin with JMP Securities. Your line is open.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress.
Jeff can you just remind us.
Why I guess, the biological rationale for <unk>, one a as it is.
The mutation and back on loss how.
You know how you went about picking these two.
Genes in particular and just related to that you know.
Is there a diagnostic development plan also in the works.
To help identify these patients or are these mutations also part of a standard.
Foundational assets one of the other assets that might be out there.
And sort of a third question related to assets.
If you look at that RNA that.
PCR profile that you had.
Where does kind of one area and back on loss fit in there or is there like a total shutdown. In this you know 137, and 185 and presumably 350 milligram doses that you looked at or is there something more nuance there.
So I'll start, but we also have Patrick trigger on the line, who will ask to kind of pick up.
I think.
On the kind of the back part of the question on the need for a diagnostic assay.
It's right now it's premature to kind of answer that question I think as we as we see kind of how the patients are.
With the with on a wild type and mutational status perform in the expansion cohorts. We can we can determine that but but these are mutations that are frequently included in and she has panels.
So we'll have kind of the data that we need to inform that decision on the biological rationale maybe Patrick if you can you can pick up that question and and provide kind of the what got you excited about these particular.
Areas.
Yes sure yes.
Yes, thanks range for the questions so areas when it is.
No it's part of the <unk>.
Chromatin remodeling protein complex turn fast one.
And the last one complex restless with the PSC to complex that Eth due as part of four gene control and in the case of the area. When EMIR two mutations easy H two can take Cobra gene control from the past one complex and it creates a scenario where the underlying gene expression probe.
Graham, It's rewired and it's the concept of the hypothesis is that <unk> two inhibition would restore.
Gene expression program debt, rather than promote proliferation, but promote differentiation and debt book doses.
So regarding the diagnostic I'd just add that what Jacobs said that Eric on Ami patients are part of our foundation.
Handle acquaintance Oh.
As they are part of many of the N G S payments that's true but.
Got it okay perfect. Thank you for that and then.
I think Jeff just mentioned on the on the call regarding additional Juno toxicity studies that had been submitted and no comments back yet.
I guess on a couple of questions. One you know what were those additional studies can you go on to provide a little bit more color and regarding the no comments back yet.
Is there do you feel like Theres been sufficient time.
That has passed that you that you feel pretty confident that.
You know the FDA has kind of check the box or do we still need to wait for some sort of confirmation letter or something that.
Suggests they they've taken a look at it and everything is good to go.
Okay.
Patrick do I take this one yeah sure.
Yeah. So as we have said previously we had.
On a positive signal in one out of the three initial Gina took ccd's assets that will brand we informed the FDA, we followed that guidance and updated our informed consent for them and our investigators brochure and then we ran some follow up studies that included an in vitro micronucleus assay.
Our call today S. A N a.
We determined that there was a real signals. So we share these results with the agency and.
They have not asked us to do anything different.
If if the regulator would belief that there is.
An issue they would have.
Coming back to us we believe that given the severity of the disease we are studying.
These preclinical findings will be acceptable.
Got it okay.
And I think that's it from me. Thank you very much for taking the questions.
Thank you. Our next question comes from Colin Cousy with Baird. Your line is open.
Hi, good morning, Thanks, a lot for taking the questions and congrats on on the progress on.
The phase one portion of debt owed to a nine study can you are you going to share what the tumor types, where that had been enrolled and I guess will we be able to see any patients that have tumors that are selected for the expansion cohort.
Hey, calling from.
Congratulations also on your new role.
At Baird, it's a pretty broad standard phase one.
30, and so there's there's lots of different tumor types enrolled.
It certainly is possible that.
Ah patient here or there that we are interested in for the phase two would also be enrolled.
As you know, it's also a kind of at the right dose levels and so it's a pretty rare event that we would see that in these kind of phase one studies, but certainly it's possible.
Okay. Thank you and thanks, that's very helpful.
And for the hematologic malignancies Youre going after.
At this point do you expect a recommended phase two dose to be the same as for solid tumors.
Thank God.
We.
Our recommended phase two doses in part picked on.
On the safety profile.
And of course, the PD profile on the PK profile.
And so 350 milligrams dosed orally once daily is the recommended phase II dose that we would carry forward even in lymphoma.
Great and I would just echo <unk> comments previously you know phase one patients have relapsed and refractory to all available therapies. So these are.
The phase one patients are not the same as other patients.
Makes sense. Thank you so much.
Thank you and as a reminder, if you would like to ask a question press. The Star then one key when you touched on telephone. Our next question comes from Joel Jay Olson with Oppenheimer. Your line is open.
Oh, Hey, thanks for taking the questions as you continue to build evidence for disease modification for Pelham Bruce.
Can you talk about whether or not that's an indication that you expect or how that data will get into the label and then can you talk about any work that you've done to prepare for the commercialization of Palo Verde and.
Remind us about the IP protection and any additional patents you may have filed.
So why don't I start.
And you know we've got I'll start with the end of the question first if that's okay.
We did we have been preparing for commercialization, it's still relatively early innings for that we do.
Did have on our our our last earnings call Brendan Delaney joined US who recently joined the company as Chief Commercial Officer and.
And Brendan will be building the team that would be eventually commercializing <unk> and so we are taking the stage appropriate steps. There. He has he had a small group of people working with him to help us with that as well as the product positioning.
In terms of IP.
We've managed to build a fairly significant IP portfolio that covers both composition as well as various method.
Method method of treatment.
Types of patent applications that we think are also significant.
And so.
So that's I think that's all mostly cut out on the public domain.
And in terms of kind of disease modification.
We spent kind of a.
I think we've taken a very.
Kind of a deliberate approach to making this the work that we've done with <unk> and manifest.
A very translational heavy study probably the biggest investment in translational science in myelofibrosis to date.
And so with that in mind, our goal is certainly to leverage those those learnings into internet effects too and if they can help us to position ourselves to to find ways to include any of those types of findings like bone marrow fibrosis or the like into a label will certainly.
Certainly set ourselves up to be able to do that as part of the way. The study is conducted.
Yeah in sugar, if I could just add I mean, the reduction in bone marrow fibrosis, and the normalization in the number and distribution of both Mega carrier sites in erythroid precursors or findings that we think are very important and so as you might imagine is triggered.
Mentioned, we might be pursuing that in a randomized setting and would be thinking about how that might be included in future promotional use. Thanks.
That's super helpful. Thank you and then is there any update on your 42 program.
I mean that program. It's still certainly early days I mean, we we just moved that into the IND, enabling studies and so we're going through all the work that would be needed to enable <unk>.
Finally on 94 that for that program. So no further update on 42 right now.
Okay. Thanks for taking the questions.
Thank you and there are no other questions on the queue I would like to turn the call back to Jakarta with Hoffman for any closing remarks.
Yeah, I just wanted to thank everybody for joining today and asking great questions.
We're really excited.
As as we mentioned earlier on on the call to take the next steps with both a collaborative as well as O to O nine in terms of dosing patients in our next studies.
We think it really sets the company up really nicely to transition from where we are today.
Two the goal towards becoming a fully integrated and sustainable organization with our marketed products as well as as well as the pipeline.
And look forward to.
Talking in future calls.
This concludes today's conference call. Thank you for participating you may now disconnect speakers. Please standby.
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