Q4 2020 Constellation Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, please standby your conference call will begin momentarily once again, ladies and gentlemen, thank you for your patience and please standby.
[music].
Yeah.
Ladies and gentlemen, thank you for standing by and welcome to the constellation Pharmaceuticals fourth quarter of 'twenty 'twenty earnings Conference call. At this time all participants are in L. A.
And all of the mode of.
The the speaker presentation, there will be a question and answer session.
Ask the question during the session you will need the press star one on your telephone please be advised that today's conference is being recorded.
We're quite of any further assistance. Please press star Zero I would now like to hand, the conference to speak of today key of California, Vice President of Investor Relations and Communications. Please go ahead ma'am.
Thank you operator Watson conference call, just got constellation fourth quarter 2020 financial of myself and the lifestyle.
For me.
Please turn to slide 10.
Before we begin I want to point out that our presentation. Today will include forward looking statements the checkbook.
Check the checking with the uncertainty.
Actual results may differ materially due to various important factors, including those described in the risk factors section as well as discussions of potential of what.
The person team and other important factors from the company's most recent filings with the Securities and Exchange Commission, including the company's each of them for them.
The 10-K for the fourth quarter and year end debt December 31st 2020, which we filed earlier. This morning, please check of lightweight and.
Now I'll turn the call over to kick off.
Thank you Keith and good morning, everyone.
I am pleased to announce that several members of our leadership team of joining me on the call today.
The first Brendan Delaney, our new Chief commercial officer, who will discuss our vision for the positioning of electricity next.
Next well hear from Jeff on free of our Chief Medical Officer.
Patrick <unk>, our chief scientific officer to describe the work that our team is doing good.
The labor said, formerly known of CPI jurisdiction as the backbone of the future net treatment or progress on C. P IV or two year nine as well as an introduction of our newest did all the candidates the CPI for it too.
And you'll also hear from him of Reed, our Chief Financial Officer, who will review the financials.
Please turn to slide four.
Constellation Division is to become the leading hematology and oncology commercial and R&D organizations.
Today, we are focused on executing on the pivotal trial that is now underway for collaboration.
Our goal is to transform the standard of care for patients with Myelofibrosis and Clinique lab received the backbone of the mess therapy.
You'll hear more about how we were moving forward towards that vision in the coming months.
In addition, we are planning to explore additional indications.
We may be able to proceed with the ladder said such as the central Thrombocythemia and others.
We believe that of broad development program could position Calabria said as a cornerstone hematology product in the future.
We also intend to demonstrate best in class of potential for C. P idea of Tuesday night are easy it's true and did the group, which is currently in the dose escalation portion of the phase one two study.
The lifeblood of constellation is our discovery platform.
And all of our product candidates have originated from the internal discovery efforts today.
Today, Patrick will describe CPI for day to the newest develop the kind of W debt like we identified please.
Please turn to slide five.
2020 was truly a transformational year for constellation.
I'd like to thank the constellation of associates for their dedication and hard work during the past year.
Importantly, we would also like to thank the patients who participated in our clinical trials and their families as well as the clinical investigators.
We presented important data updates from the manifest trial of collaborative throughout 2020, establishing clinical proof of concept as the potential first line agent.
In myelofibrosis.
Labrish it could be the first new mechanism of action for these and for these patients with MF.
Beyond JAK inhibitors, and we are excited about the potential for this candidate to transform the standard of care in the setting.
We've initiated our phase III study manifests too.
And that trial is now underway.
We anticipate having data from that study by the end of next year.
We're also advancing our pipeline of new programs.
We have described C. P. I see your two year of nine of the past and today you will hear about the next discovery program C. P. I 42, which was announced do you want inhibitor.
In 2020.
We also focused on building out our leadership team to support the next leg of our story.
Jeff Humphrey joined US as Chief Medical Officer, and we also expanded some of our development teams to support the NDA readiness.
As I mentioned, Brendan will lead our commercial team and prelaunch preparations in support of flavor said.
From a financial perspective, we were in a very strong position.
We completed a follow on for financing in June that raised almost $200 million and today, you'll hear from <unk> about the overall cash position and how far that takes us.
We executed successfully on each of these fronts. Despite the limitations presented by COVID-19.
Certainly been of trying year for the whole world constellation was able to operate in this environment and the semi virtual capacity.
Our R&D labs remained open and the team has pushed forward and advancing our pipeline.
Earlier in 2020 as was the case industry wide, we noted at our manifest trial experienced the slowdown in recruiting.
We will be watching to see how the pandemic continues to unfold going forward. Please.
Please turn to slide six.
To translate what I've just described into more of a pipeline view labor said isn't the phase three program in myelofibrosis.
The focus of that program is the first line JAK inhibitor naive patients.
The P IV or 209 is in the later innings.
Of the dose escalation portion of the phase one two trial and we hope to identify the M. P D and the recommended phase two dose in the not too distant future.
We anticipate presenting results from the phase one portion of the study around mid year.
The next program the CPI for way too, which we believe is the mechanism that can impact the myeloid biology and expand our footprint in hematologic malignancies.
Our discovery efforts are aimed at continuing to identify novel mechanisms to drive additional growth.
With that I will turn the call over to our Chief Commercial Officer, Brendan Delaney, who recently joined US from Immunomedics and previously headed up the hematology franchise and Celgene.
He will help us achieve the next level of provision it cause of constellation transition to become an integrated research and development and commercial organization Brendan.
Thank you for the kind of introduction Jigger, Please turn to slide seven.
It is an exciting time to join constellation.
I was attracted the constellation because of the opportunity to build the commercial organization that has the potential to help advance the treatment of myelofibrosis patients with collaborative.
Product with game changing potential.
Since joining the team in January I've been very impressed with the talented people who formed the fabric of this dynamic company and I look forward to attracting top tier of commercial talent, who will only add to the special culture that has been created at constellation.
In my experience commercial success always starts with the well differentiated product.
I believe the collaborative has the differentiated profile necessary to become a foundational therapy not only in myelofibrosis, but across hematologic malignancies, where bet inhibition may play a role.
With any of myelofibrosis landscape that is rapidly evolving collaborative is a first in class oral bet inhibitor that could provide hematologists with a new mechanism of action and the potential to realize disease modifying treatment effects beyond the symptom control.
More importantly, a growing body of data and clinical experience with this product candidate she'll preliminary evidence of efficacy and Tolerability both of the single agent and in combination with other therapies, including <unk>.
Moving to slide eight.
Our recent market research with U S. Hematologist has confirmed the high unmet need that currently exists in the myelofibrosis market.
The above and beyond the primary goal of achieving an overall survival benefit most hematologist surveyed who manage myelofibrosis patients state that the ability to treat with a therapy that is able to modify the underlying disease is the largest unmet medical need in myelofibrosis. Moreover, if disease modification wasn't true.
<unk>. Many hematologists stated that they would consider treating patients earlier in order to normalize bone marrow and prevent cumulative damage that could change the course of disease.
Additionally reduction in transfusion dependence and improvement in anemia are also seen a significant unmet need.
Please turn to slide nine.
Myelofibrosis is a complex condition, where overall survival is still relatively short, especially for those patients with intermediate and high risk disease.
Most myelofibrosis patients live with symptoms that severely impacts the quality of life.
Patients are very often concerned with the notion of disease progression and death.
Since being launched in 2011 rux of letting up has been a mainstay of myelofibrosis treatment and that's provided a big step forward for patients who are living with this difficult disease.
However for many patients rux of late in the mono therapy is unable to impact the course of their underlying disease, resulting in sub optimal treatment response, and relatively short durations of therapeutic benefit.
As displayed in this graph.
Is the need to move beyond spleen response, and symptom control and shift the goals of myelofibrosis treatment toward deeper and more durable responses.
As has been demonstrated in any number of other hematologic malignancies. We believe that this goal of best we achieved by earlier treatment intervention with a comedy tour real approach utilizing different mechanisms, including bet inhibition.
Please turn to slide 10.
As I have immersed myself in the myelofibrosis treatment landscape over the last few months I'm excited and very encouraged by the large commercial opportunity that exists for a new product with the potential for disease modifying effects.
We estimate that in the U S and Europe. There are between 30 and 35000 prevalent myelofibrosis patients who are classified as intermediate or high risk.
Of that group roughly half currently receives rux, a litany of therapy and of those many experience of suboptimal response to treatment with relatively short treatment duration.
In the near term, we believe that the addition of collaborative to rux of letting the therapy. They not only expand the number of patients who could benefit from treatment, but may also offer the potential for longer treatment duration through deeper and more durable responses.
Over the long term, we believe that we can further develop collaborative into it backbone of myelofibrosis therapy with the potential to shift the treatment paradigm in this debilitating disease.
Now I'll turn the call over to Jeff.
Thanks, Brendan please turn to slide 11.
As a reminder, myelofibrosis is a complex disease with for hallmarks patients typically present with the large spleen of high symptom burden progressive anemia, and they frequently become transfusion dependent.
The disease originates in the bone marrow, where abnormal myeloid cells leads to bone marrow fibrosis and reduced hematologic function.
As Brendan stated constellations goal is to develop collapses for this novel therapy for myelofibrosis. It affects all for hallmarks and can potentially be a disease modifying therapy.
Let's turn to slide 12.
<unk> is the first new mechanism to demonstrate proof of concept in myelofibrosis.
You have to register Palaver Sip is the first in class bet inhibitor for treatment of MF.
This slide summarizes our clinical and translational data presented at Ash, which were viewed very positively by our investigators and the M. P N commodity.
The waterfall plot shows that of 67% SVR thirty-five response rate of 24 weeks was seen in 63, JAK inhibitor naive MF patients given the <unk>, which is roughly twice the rate of <unk> alone and historical controls and we saw a similar pattern in the center.
Responses as measured by T S at 50.
The Spider plot shows the spleen reductions for deep and durable in the individual patients and these data support our hope to transform the standard of care for myelofibrosis the.
The translational data are particularly exciting with one of 100 chairs.
The pre and post treatment bone marrow biopsies approximately one third of MF patients receiving collapse of the cross sell first and second line treatment arms had 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 in the number of distribution of Mega carrier sites and red cell precursors.
Ex vivo studies of bone marrow from patients with MF further supported this finding these preliminary.
Mary data were highlighted at Ash in December and support our belief the clabber said may be disease modifying.
And finally, the changes in bone marrow were associated with increases in hemoglobin and the.
The increase in mean hemoglobin was greater in patients treated with Polaris of alone and from.
Collaborative was combined with trucks I'll, let net as expected.
The largest increase was seen in patients who are anemic at baseline as shown by the Orange lines.
<unk> was generally well tolerated and based on the preliminary data generated in these phase two clinical trial, we opened our pivotal study phase III manifest two in December and we are currently initiating sites I'm looking forward to enrolling our first patients.
Please turn to slide 13.
This constellation moves ahead with manifest too we've begun to swiftly build a world class Medical Affairs organization with the footprint of M of cells and medical directors in North America and Europe.
Having these boots on the ground connected with our clinical trial sites key investigators and patient advocacy organizations globally complements our efforts to establish a digital presence, which is reflected here with our manifest trial website.
And finally, we will be amplifying the data supporting the disease modifying potential of slab for said with high quality scientific communications and medical publications.
And now I'll hand, the call over to my colleague Patrick to discuss the pipeline Patrick.
Thank you Jess.
This way of moving forward with all of Phase III study.
It's the working on completing the non clinical data package to ultimately support marketing applications for <unk>.
For instance, we have now completed all of the studies to assess the genotoxic the potential of collaboration.
On our last earnings call, we disclosed that one of our preclinical studies provided positive Gino toxicity of results while the two additional studies did not.
Had previously shared these results with the FDA and the lines on updating the patient informed consent form while continuing our clinical development activities.
We also proposed to conduct two additional preclinical studies to reconcile the initial observations and we have now conducted these follow up studies.
The results show the collaboration has genotoxic potentially.
Just on a previous discussions with the FDA. We currently do not believe that these findings will impact of the development path of collab received in myelofibrosis.
In the oncology setting it is not unusual for therapies to have these types of findings beyond that we are making good progress from completing other non clinical studies needed to support NDA submission.
Please turn to slide 14.
It's just mentioned our translational data from our recent ash update on tricky and we continue to collect additional data from our phase two many of this study we plan to provide an expansive update of our translational data mid year, followed by a clinical update by year's end we will.
Update of claims of responses and the encouraging depth and durability of response to pillar of receipt.
In our attempt to provide novel therapeutic options for patients with myelofibrosis. We are engaged in exploring additional mechanisms that could help to expand the opportunity. One of these day. So it is the latest particularly of CPI for <unk> as our next development candidate for which we are now focused on completing IND, enabling.
<unk>.
For the two as an internally discovered product candidate that I would like to turn your attention to on slide 15.
We're excited about developing CPI for a two of potent and selective inhibitor of the LSD, one demethylase named zone, and let's see one commonly referred to as an epigenetic eraser removes modifications from chromatin and thereby functions in the regulation of gene expression.
Importantly, unless the one functions in blood cell development and it's required for the maintenance of him up to the extent cells as well as for the PREPA the differentiation of erythroid and Mike of Cardio Citic sell the niches.
And the context of Myelofibrosis, we believe the CPI for the two main to <unk> with the ability of malignant stem cells to replenish the pool of the bear in blood cells.
Moreover, EPS for it to make pre themes differentiation of Mega carrier site. It's cell population that is the key driver of various disease features of myelofibrosis, including the overproduction of inflammatory cytokines.
As shown on the right hand side CPI for it too has shown encouraging spleen volume reduction and survival benefit in a post MTN mouse model in which CPI for it to Outcompete the rough sleeping at CPI for a tool has a profile of different from other analysts do you want inhibitors, and we believe that our differentiated clinical develop.
<unk> strategy is aimed to expand the range of opportunities in myelofibrosis.
I would also like to update you on our efforts in developing Cpi's north of zero nine our second generation easy, it's doing EBITDA for hematologic malignancies and solid tumors.
Please turn to slide 16.
You will recall that we designed the <unk> euro Tuesday or in line to improve in the first generation easy. It's two inhibitors in a number of ways, including increased potency long residence time, and maintaining exposure levels by not inducing its own metabolism.
As discussed on our last earnings call with that type of profile of CPI Zero 209 makes track for the full therapeutic potential of <unk> two biology. Please.
Please turn to slide 17.
We are currently conducting a phase one two study with CPI of 209 for patients with advanced hematologic and solid tumors.
We have completed multiple dose cohorts and have seen the dose dependent increase in exposure with no evidence of induction of compounded metabolism.
We have also seen dose dependent increases in target engagement as measured by the assessment of multiple pharmacodynamic markers.
Shown here of gene expression profiling data from the blood of patients in the first four dose cohorts, whereby we compare the baseline gene expression with the expression of genes of day 22 of the first treatment cycle of once daily CPI of 209 treatment.
The heat map on the left shows easy edge to target gene expression, whereby low and high expression are indicated by blue and red colors, respectively.
It is encouraging to see that the magnitude of gene expression increases with increasing doses of <unk> Your line.
We believe that the performance of CPI zero to zero in line with respect to modulation of Pharmacodynamic markers.
System with our aspirations for our compound with best in class of potential. Please.
Please turn to slide 18.
I would like to leave you with the reminder of some of the context that we are interested in for the initial development of C. P argument to the zero nine the illustration on the left shows molecular context of sweat genomic collaborations create the functional dependents on the easy it's too such as gain of function mutations in easier to itself as observed in certain subsets of the.
Soma all of loss of function mutations in chromatin regulatory proteins, such as area of the money or best one as observed in several solid tumor indications.
We also continue to be interested in the exploration of prostate cancer as an indication for <unk>. Your line based on functional cooperation of how easy. It is true inhibitors with E R or the androgen receptor targeted agents in prostate cancer models.
After establishing safety and determining our pizzuti, we plan to move rapidly into the phase two portion of the trial to test the CPI youre of Tuesday or of nine therapeutic effects in the east well defined cancer context.
And now I will turn over the call to Emma.
Thank you Patrick and good morning, everybody moving on to the financials on slide 19, we had a net loss of $37 $4 million for 79 cents per share in the fourth quarter.
Out of $126 $4 million or $2 81 per share for the full year in line with our expectation.
Our cash cash equivalents in marketable securities at year end of $421 $4 million.
Sufficient 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 the collaborative and to start building the commercial organization needed to launch the product candidates.
Well as to explore the utility of collaborative and other indications.
In addition, we have sufficient funds to complete the phase one two clinical trial for CPI of two of nine as well as to progress out of discovery and preclinical pipeline of compounds and found out general corporate operation.
Turning to slide 22.
To summarize we believe constellation is well positioned to execute and maximize the value proposal.
We have multiple clinical stage assets, including our phase three asset collab with it.
All of our programs the whole.
The significant IP protection.
The loss of exclusivity for the collaborative extends beyond 2035 in total.
The Italian two of nine beyond the 24th.
We also believe we have the pipeline opportunities within these product candidates with the potential to expand into multiple indications.
And we have a robust discovery engine to fuel long term success of the company.
Lastly, and importantly, we are well capitalized it will allow us to execute on our product development plan.
Overall, we're very pleased with the position that we're in.
Please turn to slide 21.
Our corporate milestones for 2021 of listed here.
Yeah.
These include further updates from our phase two clinical trial manifest for the cancellation of a lot of things in the immediate timeframe and the clinical update by the end of the year.
We also aim to provide an update on the new expansion of the close by the end of the year.
The CPI as two of nine we plan to provide an update from the phase one portion of the study by midyear.
As Patrick said, we expect the moving to the phase two expansion cohort shortly after determining the dose.
Back to provide an update from the from those cohorts by the end of the year.
That concludes our prepared remarks. This morning, so I'll turn things back over to the offering for.
Operator could you. Please open the line for questions.
Thank you ladies and gentlemen, if you have a question at this time. Please press Star then one on your Touchtone telephone hit for your question has been answered or you wish to remove yourself from the queue. Please press the pound key to prevent any background noise. We ask that you. Please push from line on mute. Once your question has been stated.
Our first question comes from the line of of harm Rama with J P. Morgan. Your line is open. Please go ahead.
Hi, guys. Thanks, so much for taking the question for.
For Oh 610 update in additional indications here by the end of the year.
Is this going to be more of a strategic update or will be will there be any sort of clinical data involved what are the indications on the table here I think you've previously talked about ETE.
Thanks, so much.
And the problem. Thanks, Thanks for your question.
It's good to hear you.
So we're trying to get going and ETE and that's an area that we think that theres. Good rationale for based on some of what we've seen in.
The manifest study.
And it's possible that we may have some early data by the end of this year, although I think that the lion's share of the data that would be pivotal trial of enabling is more of about 2022 of that.
And then in terms of additional indications, where we're not quite ready to go into the details of them, but but I think.
Some of the translational data that we've generated.
You know in the manifest study, particularly pointing to the red blood cell biology kind of points in the direction of diseases, where in the near the issue as well as transfusions and issued so so more on that as we as we finalize those plans and get those studies up and running.
Thanks, so much for taking a question.
Thank you and our next question comes from the line of Marc Frahm with Cowen and company. Your line is open. Please go ahead.
Hey, guys. Thanks for taking my questions, maybe just from the confirming the toxicity can you.
Some of the doses that that was being seen and in these preclinical assays and how that exposure.
The compares to what you're achieving in patients and then related to that.
Do you think it's possible that that gene toxicity is actually beating some of the efficacy signal day that you see given the that is the mechanism of action of some chemotherapies.
Patrick do you want take this one.
Sure happy to.
Obviously you're required by.
Carrying out the studies to go to very high concentrations that are <unk>.
<unk> concentrations that you're using in the clinic, but.
Regardless.
But the Youll see it at a high higher dose, though at the lower dose any kind of course of D. D. D. D study.
<unk> is determined thing of study drug is having Gina talk to the potential.
And we.
<unk>.
On the on the second part we do not believe that the peanuts toxicity that we have seen them mute some of the efficacy and actually we we believe that.
We are having more of a positive impact on rates of the sell both red blood cell biology, rather than a cytotoxic impact.
Does that day and meet with many of them.
Yeah.
Yes.
The if I can also just jump in the.
Margaret Thanks for noting some of the for the other agents.
That happens you can talk to the potential but I think it kind of in the context of malignant diseases like this.
He noted several chemotherapeutic agents flattened quite a few.
All these all of these are all positive and these assays, but even more targeted therapies like the wrapper red light.
Elected bortezomib, even gleevec and importantly, the Hydroxyurea, which is very commonly used in throughout MTN and EBIT and benign teams.
And we've also kind of some some non oncology diseases.
The bupropion.
You can from chickens for migraine that had these findings. So so it's not uncommon to see these types of results in.
In drug development, and particularly in malignant diseases.
Okay great.
That is helpful.
And then.
Here with your guidance to have data from manifest to them.
The likely by the end of next year is that assuming the resizing mechanism is triggered or is that assuming the.
The trial phase as originally designed.
Yeah that that.
I'm not sure it's going to be a huge impact either way.
If we did decide to upsize it.
But but but the base guidance is based on the currently designed study of 310 patients.
That's right okay.
Thank you.
Thank you and our next question comes from the line of credit a D var of kind of with true of Securities. Your line is open. Please go ahead.
Thank you so much and congrats on all of the progress last you guys.
These are the early stages of enrollment for the phase two trial, but I was wondering if you can tell us a little bit of luck, what youre hearing from your investigators about enrollment.
One of at on your Ash Investor calls one of the Kols have talked about how he is a bolus of patients ready to enroll for the trial do.
Do you expect this bolus to impact the trajectory of enrollment in any way. Thank you.
Jeff did you want you guys think you can comment on yeah.
Yeah. Thank you for the question, but we we have you know we've we're in the early days of opening the manifest to trial. Our investigators have shown a lot of enthusiasm and are anxious to get started we have identified sites that do have these policies of patients.
Enrollment as you know typically is slower in the beginning ramps up and reaches the maximum and.
I think we'll see that play out with manifest too.
We've put in place a medical affairs team true.
Capitalized on the investigator investigator enthusiasm and identify the sites with patients waiting for treatment.
Thank you.
Okay, and if I can ask a follow up I'm just curious of the patients.
The expected to be enrolled for the trial of IV considered at risk patients and Mike how does COVID-19 vaccination playing to the trial.
Yeah. Thank you the average age for myelofibrosis in the seventies. So it's a it is the population that is at risk.
This is the population that's likely to be vaccinated first early.
For the wave of vaccinations.
How it actually plays out is something that we'll have to solve the overtime.
Okay. Thank you.
Thank you and our next question comes from the line of Mike Goss with Barrington. Your line is open. Please go ahead.
Hey, guys. Thanks for taking the question just a quick one on Palo breath of the.
You guys mentioned, providing some translational update mid year, just maybe if you can talk about some of the day do you plan to share there and will there be should we expect it would be sort of similar to what we've seen previously at ash, we have additional endpoints and analyses to sort of share as well.
Hey, Mike.
Thanks for the question.
So I think it will be of data heavy kind of translational update.
At the at the kind of mid year update.
Picking up on some of the findings, but maybe Patrick do you want to go into <unk>.
More about kind of kind of how you are anticipating that rolling out.
And as well as kind of alluded. The later you update as well.
Yeah sure happy to so.
We definitely want to build on what we disclose the ash with respect to the bone marrow findings that we reported on Inc.
To increase that dataset, but we definitely have playing to our sort of report an additional molecule of endpoints and how they relate to two of the Dcs and the clinical endpoint.
Great. Thank you.
Thank you and our next question comes from the line of two Kim with BMO capital markets. Your line is open. Please go ahead.
Hey, good afternoon, everyone. Thanks for taking the questions. This is terry on the per DAU.
First one is on the celebrates the in terms of the manifest through enrollment.
Are you guys capturing patients that would essentially fall under that the two set of panic and anemic the star of rope.
Kind of help you know expand the addressable population that.
Brendan was kind of the discussing earlier on the call.
And then my next questions are about the for it to.
Yeah, I can take that question. So within manifest we did have enrollment criteria that permitted anemia and in fact the.
The median hemoglobin for patients.
Patients enrolled on the manifest study was 9.1, we also permitted patients to enroll with platelet counts 200, and the criteria for manifest who are slightly more liberal other than that so I think the answer to your question is yes, we will be seeing patients with the anemia and thrombocytopenia.
Yes.
I believe that state your question yes.
No no you hit it I.
I appreciate the clarity.
And then for for it to can you kind of discuss the little bit of about the the.
The actual molecule in terms of if it's a reversible or reversible inhibitor and potentially what the drawbacks or for either approach and.
In addition to the debt.
Essentially the contrast, your molecule to some of these other.
We've seen in the clinic.
More specifically, our margaux, which is going down debt clinical development paths of.
N P and with it the trials in 18 of them out.
Yeah.
I'm happy to take that one so like.
Like I said before I think we have a.
The reasons to believe that CPI point, we defined at this point, we haven't disclosed really the properties of the compound all of our clinical development strategy with playing them doing this at one point down the road.
Well, we are definitely aware of of the L. S. C. One inhibitor in the clinic can be intrigued by the clinical.
Data and the clinical benefit that was shown and that helps us to inform our development.
Pat.
I think we of a group we have repeatedly shown that with all the work on the beta inhibitor and the easy it's doing here because we were able to deliver best in class of molecules with the differentiated development path.
In the highly competitive environment and we hope.
That this could be the same here for CPI for it to any of the coupons.
Okay. It sounds good I'm looking for it to the additional information of the future. Thank.
Thank you.
Okay. Thank you.
And again, ladies and gentlemen, if you have a question at this time. Please press Star then one and our next question comes from the line of Jay Olson with Oppenheimer. Your line is open. Please go ahead.
Oh, Hey, thanks for taking the question.
Could you maybe talk a little more about how you intend to prove disease modification for Palo breath of and.
Do you ultimately expect to have a disease modifying claim in the FDA approved label for Palo breath of them. Thank you.
Patrick do you want to take that one.
And then maybe maybe Jeff can you can tag on.
Yes.
Yeah. So so obviously, but you know what you have seen at the Ash conference.
We have disclosed some really intriguing observation in the bone marrow of the patients treated for about 24 weeks with with collaborative either alone or in combination with the rest of the lithium. So I think this is an evolving data set we are definitely one of put ourselves in contention to be able to.
The capitalized on improving.
Improving bone marrow.
The <unk> function, but it's too early for us to kind of delineate how.
How that would impact our regulatory strategy.
But maybe just to kind of add I think the the.
FX that we see and kind of again, what we hear from physicians is that the bone marrow result is really exciting so.
<unk> in a solid tumor when you can tell the patient that their tumor shrinking.
You can tell of patient who has disease bone marrow debt appealing.
The next potentially very powerful and then when you can connect the dots between that and some of the clinical findings like hemoglobin increases.
You know that starts to kind of form the picture for for how you can start the message around disease modification.
And that's really a lot of what we plan to be able to do with the the data that we are continuing to mine from the manifest study.
And importantly, Jay as you kind of.
How do we how do we how do we think about that benefits to that could potentially lead to kind of regulatory discussions. It's a little early for us to kind of comment on on the.
Net in totality, but it certainly.
Part of what what we would intend to do with the registration.
Strategy unfolds.
Yeah, great. Thanks for if I could add yeah, if I could add just briefly the bone marrow fibrosis as an independent predictor of the overall survival.
Independent even of the it started tips at risk classification, but and.
And we have seen this reduction in bone marrow fibrosis at six months, which is high.
It is important.
And beyond that we've also seen the effects on Mega carrier side as the topography and changes in red cell precursor.
We also feel represents a drug can tacked onto the cell of origin for this disease.
And that really does give us reason to believe this could be the disease modifying.
Thanks.
Thank you.
Yes.
Thank you and I'm showing no further questions at this time I would like to turn the conference back over to check or for any further remarks.
Well thank you so much.
The two to all of our investors, who took the time to listen here.
Really appreciate it giving you the update on our 2020 of which is a very transformational year for us and we look forward to continuing to execute and.
In 2021.
And deliver on what we think could be a potential game changing therapy in collaboration.
And also the unfolding pipeline, which provides multiple opportunities for us to deliver a novel.
Novel treatments to patients. So thanks, everyone again and talk to you all soon.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect everyone have a great day.
Okay.
[music].
Yeah.
Yeah.
[music].
Yeah.
The.
Yeah.
Okay.