Q2 2020 Scholar Rock Holding Corp Earnings Call
Ladies and gentlemen, thank you for standing by welcome to the scholar Rock management intro and second quarter 2020 financial results and business progress conference call.
At this time, all participants on the listen only mode.
So to speak of presentation, there will be a question and answer session.
The ask a question during the session you would need to press star one on your telephone.
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I'd now like for hand, the conference over to your speaker today, the Catherine Hu, Vice President Investor Relations and corporate communications. Thank you. Please go ahead.
Good morning, and thank you for joining us on today's call to provide an update on second quarter 2020 financial results as well as an introduction to our newly appointed President and CEO Tony can easily.
Yes.
This operation headwinds.
Johnson, our Chief Medical Officer will also be joining told you tried on today's call.
So what's implied for this call can be accessed on the events and presentations section of the Investor Relations page on the solar off last night.
Before he told me I wanted to know that during today's call, we see making various statements about.
Future expectations plans and prospects that constitute forward looking statements.
Purposes at the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by any forward looking statements as a result of various important factors. Therefore, we discussed in his section entitled risk factors in our quarterly report on form 10-Q.
Well the other important factors and so on future filings with the Securities and Exchange Commission.
Any forward looking statements represent our views only have to say naco relied upon as representing our views of.
Security.
We disclaim any obligation to update any forward looking statements unless required by law.
Thank you and I'll now turn it over to Tony.
Thank you Catherine.
Everyone for joining us this morning.
Smaller boxes that inflection points the company's science is beginning to prove its potential clinical utility.
Our programs are moving quickly stored multiple data read outs.
And the company has new leadership to.
Next is.
Let me tell you a little about myself and why I have enjoyed solid talk at this time.
As described on slide three I was most recently president and CEO of terrorists I owe a development stage oncology company.
That was acquired by Janssen Pharmaceuticals 2019.
Before tariffs I served as president and CEO.
The company and broader.
Global commercial operations that Biogen.
I bring extensive experience. It later stage drug development and commercialization both of which are rapidly becoming quite old ASCO Sox success.
No I provided both strategic and operational leadership to life Sciences companies in times of great transition of the growth.
That is the profile with a solid onboard with sneaking to replace our founding see Oh gosh.
This was a very quite evident purposeful transition that instills confidence in the future.
That's exactly what I was able to break on 10 miles as our CFO and had a business operations almost immediately could also signal.
Transition to the belfield for success.
[laughter] served on our board for nearly two years. After it was a company well you'll hear from Ted shortly.
Oh that'd be described what drove me to smell.
Our whole science, great programs and talented people.
I've been impressed with the level of execution and collaboration and the business to take on targets as we work toward the goal of changing medical practice.
The patients suffering from cancer intramuscular disease.
My conviction on the scientific platform and programs has only increased.
As I fully immersed into the called the company.
So it's going to slide four in her presentation by top three take away is our first the scientific platform has produced multiple programs with significant therapeutic potential.
Our two both it yes, probably I'm, sorry, what Faade and that's okay wait one arts ethane quickly it both address markets that are well the both developed and growing very rapidly.
There are multiple programs at multiple milestones that that offers your and long term value inflection points as well as significant strategic optionality.
I can clearly see ox broke the tonnage all this I asked this highly differentiated the clinical programs are well designed as you will see on slide five we're moving quickly to or multiple milestones over the next 12 months.
That will elucidate each programs potential to help patients with serious diseases.
I believe this slide captures the breadth and depth of our pipeline it demonstrates the power and productivity of our scientific platform and our talented sizes.
It's also illustrates the key factors that drove by this is the joined style box.
So I went up one slide in spinal.
Muscular atrophy or else at night.
We will be reporting interim results from the ongoing Topaz phase two trial in the fourth quarter.
Followed by 12 month data the first half of 2021.
Our goal here is to establish a circuit on one side as the first muscle directed therapy for patients affected by us.
That's where basic rapid progress is building momentum on the drag in phase one trial for S. arcade what eight one.
That's all therapeutic backbone to cancer immunotherapy.
We are advancing two parts 82 of the study this quarter.
Alleyway, that's why one in combination with checkpoint inhibitors as.
Well provide an update on dose escalation next quarter.
We believe we have the tower to unlock the key to I bought the power of checkpoint inhibitors.
We are the first and only company specifically target the TGF beta one ISO form, which we believe has the potential to approve efficacy.
Well minimizing risk adverse events, we believe that historically, what I want.
Has the best potential to increase response rates the checkpoint inhibitors.
And change the medical care for cancer patients across multiple solid tumor types.
Hi, there shouldn't be these two clinical assets there are many potential opportunities for us to extend our science, whether it's additional indications additional tumor types or treatment settings for additional growth factors Argus.
Furthermore, we have an important partnership with Gilliat around fibrosis, which continues to progress well. This collaboration is it other proof point.
The attractiveness of our platform and our approach.
So with that I will turn it over to young our Chief Medical Officer Yum.
Thanks, Tony.
What do extend another warm welcome to you and Ted.
Thanks, everyone for joining us on this call today and I'm very excited to provide an update on the great progress, we're making across all of our development programs.
First I want to say, how proud I am of the team's dedication and commitment to advancing our clinical program and how appreciative. We are of the high level of engagement from a clinical trial investigators and study sites. Despite the challenges of the ongoing Kobin 19 pandemic.
We continue to make right stride or its important read outs for both the after K Olin five and that's our K 181 program.
Starting with our most advanced product candidate as her KLM by which they fully human monoclonal antibody and highly specific inhibitor of the activation of pro enlighten my answer that.
Our goal is to establish as for K a onefive.
The potential first muscle directed therapy, and promote a clinically meaningful increase in motor function or patients without them.
As outlined on slide seven.
We view that estimate treatment landscape as being classified into two distinct my complimentary therapeutic strategies.
Summon up regulator therapies.
And muffled directed therapy.
Over the top tier there have been advances in the development. That's a man of regular therapies also known as ethylene cracker therapy, which are aimed at addressing the eseven deficiency in order to prevent further motor neuron deterioration.
Well the other benefits therapy represents important progress.
Hi, my benefit of such an approach appears to be the stabilized once disease course.
Even with early intervention individual continues to have motor function impairment.
As complete correction of the disease manifestations, it's unlikely.
Therefore, we believe that a second category of therapies, namely muscle directed therapy.
It needed to aimed at driving absolute improvement in motor function.
This need for therapeutic advances to go beyond cement up regulators is highlighted by data from the phase three Terry.
If the person and later onset estimating as shown on the right hand side of the flight.
Patients treated with this one earth and 15 months experienced a mean improvement from their baseline a 3.9 points on the expanded Hammersmith functional motor skill or age messy.
Joining green.
Well. This result, it's certainly viewed as clinically meaningful.
It was still significant room for improvement and motor function as a good by the grey gradient area.
Taking a deeper look at the parity trial on slide eight.
It is evident that the improvements in Hammersmith scores predominantly occurred in patients who were treated at a very young age.
In contrast.
You can score age five and older at the time of Nusinersen indication appeared to primarily experience a stabilization with less than 15% able to achieve at least a three point improvement even with 15 month and this nursing treatment.
Hey, three point improvement in the Hammersmith scores in a given patient is widely considered to be clinically meaningful and a very favorable patient outcome as compared to the usual course the disease.
A similar phenomenon of motor function civilization was observed in the something trial with the plant in patients with type two more non ever for anti Threea me between the ages, two and 25 as shown on the right hand side of the flight.
The primary endpoint in this trial is a different motor function scale.
32 score over third over 12 months of treatment.
Well the primary endpoint with bad most patients over the age of by did not contain a three point improvement.
It's motor function stabilization phenomenon was also observed across all patients in the SUNFISH trial in the Hfm Buffy secondary endpoint, we showed a mean 0.58 point improvement.
Over placebo, which was not statistically significant.
To reiterate.
That's a minute regulators represent an important advanced for the treatment of estimate at these agents prevent further motor neuron deterioration and stabilize the D. These course.
Now the stages said for the next era of estimate drug development, that's likes to drive motor function improvement.
For the vision, we believe that's okay 015 has the potential to beat the first muscle directed therapy, SMB and potentially become the backbone of treatment to any adamant regulator.
With that backdrop, let's now turn our attention to that's okay, Olin five and the ongoing capacity to trial.
We have made substantial progress on the path fourth investigating the therapeutic potential that's okay on five as outlined on slide nine.
We formulated a strong translational rationale for investigating might that blockade enough for me.
We have demonstrated therapeutic effect preclinically and the S amendable to seven mouse model.
We have completed a phase one trial in adult healthy volunteers.
That showed initial safety.
PK profile that supports the every four week dosing regimen, we are evaluating in the Topaz trial, and importantly, PD data confirm robust engagement of the target of S.R.K. on site.
Late in form of <unk>.
Deliver TD data from the Topaz trial demonstrated this target engagement in patients with estimate as well.
We are far along on the development pathway for Caylin, five and look forward to the interim efficacy and safety analysis conducted in the fourth quarter.
Turning to slide 10 to review the Topaz trial design.
The phase two study consists of three parallel cohort.
The valuating a distinct a population of patients with type two and type three SMB.
At the beginning of this year, we complete enrollment of a total of 50 patients in the U.S. in Europe.
More specifically ctwon enrolled 23 patients with ammo Tory type three estimate between the ages the five and 21 these patients either treated as our K L. One five as a monotherapy or in conjunction with interpret about them enough regulator.
Core to enroll 15 patients the type two or don't have a prototype three yesterday also between the age of the five and 21 and all patients are treated with that's working on five in conjunction with improved got them enough regulator.
Couple or three enrolled 20 patients with type two estimate age to an older and what initiated treatment with an approved summing up regulator before five years of age.
All patients this study or Steve I B.S.R.K., a one five dose every four weeks.
12 month.
The primary efficacy endpoint plant to be body within the took that they are.
Our the expanded Hammersmith functional motor skill for H., App and messy in short we're not ever at me.
And the revised Hammersmith scale for ARIKACE in short, we're able to target.
The H. up MSC is a validated outcome measure that typically design for assuming it's often used in clinical practice and clinical research and served as the primary efficacy endpoint previously used in the phase three cherished travel nursing.
Yeah, I guess is very similar to the extent messy, but some modification to tailor just happens to patients where ambulatory.
So I'll walk through our expectations for the six month interim analysis, which we expect to receive and disclosed in the fourth quarter of this year.
We're planning for a robust read out looking across efficacy and safety endpoints.
Starting with Cort one on slide 11.
We will be looking at the name change from baseline in revised Hammersmith scale.
S.R.K. a one five treatment can indeed lead to absolute improvement in motor function over baseline rather than merely just things like making.
We will also evaluate the proportion of individual patients achieve at least a three point improvement in RHS for baseline.
To reiterate a three point improvement in a given patient would be unexpected and most patients. It's also widely considered to be clinically meaningful.
In addition to RHS, we will also be looking at times.
So just the six minute walk to the 10 minute walk I mean are walking run and time right before.
While our base assumption is that someone correction through enough summing up regulator will be necessary to complement the effect. That's okay on five in this patient population.
It'd be interesting to see if that's okay owned by monotherapy they have any impact.
For core too we will be looking at the mean change from baseline in a kept fantasy and will also evaluate the proportion of individual patients with pain at least a three point improvement in a tough M. A C over baseline.
We will be evaluating additional outcomes, including myself or my model or wrong in short.
And the World Health organization Motor development milestones.
Core threed enrolled a younger patient population investigating the potential benefit that's our K O. One five in patients who were initiated on this nurse and before the age of pipe.
We're also conducting dose exploration this colored by seeing if a lower dose they still offer meaningful efficacy.
Well the looking to see treatment can lead to substantial improvement in each of them nothing.
In addition, we'll be exploring for potential differentiation of therapeutic effect between the two delstar such as the time course in onset of therapeutic effect.
Additionally, patients will be evaluated on be wrong, and who motor developmental milestones.
While we were enthusiastic about that's okay on five perpetual in all three cohorts, we should know.
Each of the three cohorts evaluate the different estimate subpopulation, which there are a sizable number of patients and there was high unmet medical need.
The demonstration of proof of concept for any one of the three cohorts would therefore be an important result to us and would also encourage us to broaden the subsequent investigational besser caylin five to a broader population of patients would there be a wider age range or in combination with any approved estimate up regulator.
In addition, a successful proof of concept result in color three when encouraged us to further evaluate that's our K O. One five therapeutic potential in the early intervention setting the pace with type one estimate or presymptomatic individual.
Furthermore, we believe very positive efficacy outcome across any of the three cohorts would validate the motor function building hypothesis, but that's okay. One five and support the investigation as her kay outlets by therapeutic potential in other neuromuscular disorders, which probably fiber deficits when it came role.
Before turning to allocate money one I just want to remind everyone that while all patients receive active treatment for K Olin five is the Topaz trial, we are firewall from the efficacy data.
We are eager to see the intermodal and look forward to share the data with you in the fourth quarter.
At the vital now.
As of August for.
Eight patients with completed the entire 12 month treatment all eight have elected to enroll in the voluntary 12 month extension study.
Now, let's discuss effort cable anyone.
Our highly selective inhibitor to get paid one which we believe has the potential to increase response to checkpoint inhibitor therapy, and maybe the backbone of a new era of cancer immunotherapy.
Turning to slide 12.
Well checkpoint inhibitors have revolutionize the treatment of a wide range for cancer.
This therapeutic approach is only effective approximately 20% of patients.
So the central question in immuno oncology is what is driving the lack of response to checkpoint inhibitors. The most patients.
As highlighted on slide 13, the science in this arena is moving fast and evidence is mounting the implicates TGF beta one as a key culprit in driving prime or existing anti PD, one and two anti PD one therapy.
For example.
Observation was made by researchers at genetic that identified an association between increased TGF beta one level than signaling went in tumors.
And the lack of response to checkpoint inhibitor therapy as was reduced survival outcomes in patients with Urothelial carcinoma.
Mechanistically tumors with a new Munich would it be inside that has to say tumors in which T cells accumulate around the perimeter tumor, but they also effectively infiltrate into the tumor reconcile.
I've been observed to be less likely to respond to checkpoint ever therapy.
And TGF beta have the implicated in driving if you excluded phenomenon.
These emerging insights have captured the attention of industry.
Just last year, GSK, and Merck Kgaa announced the global alliance to jointly develop and commercialize a bi specific molecule that target, both TGF beta and anti PDL one.
And NPD open.
Merck acquired Telus therapeutics to develop antibodies that modulator pick up better.
As detailed on slide 14.
The therapeutic potential blocking TGF beta towards an aim overcoming checkpoint checkpoint inhibitor resistance, maybe broad across many different type of cancer.
Earlier this year about publication immunity delineated then a substantial proportion of Paul tumors.
EBIT and immune excluded phenotype.
And we ourselves.
Ducted analysis of human tumors through the T.C.G. a database.
And found that the TGF beta want isoform, what the predominant isoform in most solid tumors.
So an exciting therapeutic hypothesis has now emerge.
Blockade of TGF beta, particularly teacher no one.
Has the potential to overcome checkpoint inhibitor resistant.
And thought this combination therapy approach has the potential to substantially increase the response rates immunotherapy.
Turning to slide 15.
There were several fronts the targeting ticking up you know whether through alike and trap.
Hi specific.
Through nonselective antibody for small molecule.
We believe.
That's okay, what eight one.
Offers a unique and potentially optimal approach to targeting the TGF beta one pathway.
As for K 181, it's a fully human monoclonal antibody designed to bind to address the activation of lean TGF beta one with minimal or no binding the late and teach a bit too and latent TB beta three isoform.
Because of its all activity for the TGF beta one isoform.
That's okay 181 may offer the potential to increase the therapeutic window I avoiding toxicities associated with non selected TGF beta in addition.
In addition, we view, having an antique if they didn't want agent as a distinct molecule rather than be physically linked with the checkpoint inhibitor.
Potentially could offer advantages over by specific approaches.
By enabling pairing of Essar cable anyone with a checkpoint inhibitor that may be more optimally suitor for a given to me or indication as well and enabling the optimization of dosage for each individual component of the combination therapy.
Turning to slide 16.
The rationale for investigating as our K 181 therapeutic potential in immuno oncology is strong.
The body of evidence implicating TGF beta on pivotal role and checkpoint inhibitor resistance continues to grow.
Momentum in assigned to feel it's a salary and we believe that our essar came when they want program is well positioned to pursue and investigate it's exciting hypothesis.
This is locked up inhibition of the teed up they don't want pathway.
That's okay wasn't one offers the potential overcome the toxicity associated with nonselective inhibition teacher and.
And therefore, the potential for greater therapeutic window to permit more robust dosing against this target.
And Preclinically, we have observed the inhibition of the tier one pathway in combination with anti PD, one therapy leads to significant anti tumor responses in multiple mouse tumor model.
Now, let's turn to the Dragon Phase one trial on slide 17.
We met dosing in this trial in the second quarter and are encouraged by the engagement of the trial investigators and the pace of the trial progression, particularly against the backdrop for the Covenant 19 pandemic.
Let's walk through some of the highlights of the driving trial design, which groupon significant input from a call. He thought leaders and clinical trial, it and which offers the potential for early and frequent efficacy and safety readout.
The trial is enrolling patients locally advanced or metastatic solid tumor and is comprised of two part.
The part a dose escalation portion of the trial will evaluate after Kate I think one as a monotherapy as well as in combination with anti PD, one or anti PDL one therapy.
The park eat healthy factor portion of the trial will evaluate the anti tumor activity of Africa anyway, one in combination with anti PD, one or anti PD one therapy in four parallel to Mccord.
Slide 18 provides a more detailed look.
Part of the Doug I can try.
We have been dancing dose escalation of effort K, one in one single agent or a one of the trial.
That's part one and part two of the trial are designed to provide staggered fashion, we expect to initiate a two of the trial this quarter to evaluate ever came on at one in combination with anti PD, one or anti PD one therapy.
Part a two totally three plus three dose escalation design.
Well the primary focus of this portion of the study it's on evaluating the safety of us or 21, there is a potential for observing early efficacy single.
To illustrate each enrolled patients will have to have a document a history, a checkpoint able to resistance.
Fine by lack of response at anytime anti PD, one or anti PD one therapy.
Given patient goes on to subsequently have an anti tumor response.
On combination treatment with Turkey, when it fun that result would not be consistent with the expected clinical course and could be attributed to the addition of Essar K one.
As a result, we could potentially observed efficacy signals, even with relatively small patient numbers.
Moving to part B of the driving trial and flight thinking.
This will consist of four parallel cohort each enrolling up to 40 patients with primary resistance checkpoint inhibitors to evaluate the therapeutic potential of as Turkey anyone in combination with anti PD, one or anti PDL therapy across multiple solid tumor type.
For non small cell lung cancer and feel your carcinoma will be enrolling patients, but that was very primer resistance to pembrolizumab and for melanoma, we applied to enroll patients let's jump priorities. This is either pembrolizumab arc doubling up.
Okay.
If we observe anti tumor responses falling combination treatment for came when it. One then we believe the therapeutic effect maybe attributable to the addition of SRT money at one.
We believe this part B design love potential for rapid path to proof of concept with multiple opinion efficacy signals across multiple tumor type.
Given the high unmet need in the context of patients the primary resistance a checkpoint inhibitors.
Strong proof of concept signal could also support inefficient drug development path towards the longer range goal of registration.
We are pleased for the progress to date in this trial.
Despite the impact of the ongoing Copenhagen endemic we are moving expeditiously.
We plan to provide an update on dose escalation progress in the fourth quarter. This year airplanes initiate part b in the first quarter 2021.
Anti tumor efficacy and safety data expected started in 2020, starting in 2021.
Before I turn it over Ted.
I want to thank the team our study investigators and sites out as well all the patients participating or clinical problem.
Together I hope, we can work toward achieving our aspiration of transforming medical care for individual suffering from estimate and cancer.
Pad.
Thank you young.
Right, Tony I felt by describing why I made the decision to join Stahl look this is a dynamic time for stock at the company is growing and advancing quickly and we were just months away from some important clinical data read outs.
That could lead us to potentially initiating a registrational trial as early as next year subject to feedback from regulatory authorities.
I'm excited to apply my expertise as a senior financial and operational executive at late stage clinical and commercial stage biopharmaceutical company to skywalk as we advance our important clinical programs.
Ultimately the goal is to commercialize our therapies for that we can help the broader set of patients indeed.
I look forward to partnering with Tony Young and the rest of the executive team to begin the long range strategic planning necessary to execute our ambitious plans.
Furthermore, I had the our children Skywatch board of directors to nearly two years before joining a CFO and head of business operations last month.
The gave me a clear view into the many accomplishments for the company and is also I have a high degree of confidence in the scientific platform the clinical programs and the team's ability to execute.
Now, let's turn to slide 21 to highlight second quarter GAAP financial results.
Revenue in the quarter was approximately $4 million and was it exclusively related to go we had corporation.
R&D expense was approximately $17 million in the second quarter compared to $14 million in the prior year quarter.
The year over year increase can be attributed to the ongoing topaz as our cable one I've trial, a payment to specific for the delivery and acceptance of a customized anti body display library as well higher personnel related costs.
Do you an expense was approximately $6 million compared to just just about $5 million for the year ago quarter.
This year over year increase was primarily the result of personnel related cost and professional services.
Net loss for the quarter was about $19 million.
Well for 65 cents per share. This compares to net loss of $12 million, all 48 cents per show for the quarter you'll go.
To summarize our spending for the second quarter and the first half 2020 was aligned with our plan and is focused on advancing our clinical development programs investing our research and discovery platform with ambitious with ambitions to generate many more clinical stage products in the future and investing in DNA capabilities.
In support of expanding R&D infrastructure.
As of June 30, 2020, we had cash and cash equivalents in marketable securities of approximately $141 million versus 157 million at the end of 2019.
Our current operational plan points to a runway to extend into the fourth quarter 2021.
To wrap up my comments, we believe that Oh, we have a productive scientific platform and we'll continue to invest our drug discovery efforts to feed the pipeline.
We have two ongoing clinical trials as our K is on the cost both important value creating milestones.
Hey, White, one is moving quickly towards clinical data as well as we believe it has immense potential to change the treatment landscape for cancer patients.
And on top of these clinical programs, we have a lot of optionality in terms of next indications.
Simply there was lot going on and many great programs for us to investing.
Now I'll turn it back to Tony for some closing remarks Tony.
Thank you Ted to close on one [laughter] impressed I am with the progress the company is made especially against the backdrop of this ongoing.
It's coming back to slide 22 that next six quarters are filled with a number of important R&D milestones that we'll continue to boost the potential.
Of our programs and our scientific platform.
We are very much looking forward to providing updates from both the SRT Oh I'm sorry.
Sorry, but I want.
Order.
And based on our achievements with our scientific platform I'm confident that we can take on some of the toughest targeted medicines, so that we're patients get benefit.
I want to thank my colleagues for their hard work dedication.
Patients who are awaiting therapies and I also want to thank our shareholders for their support and this morning.
I think we could I will turn to Q and <unk> operator.
Thank you Sir.
As a reminder to ask a question you would need to press star one on your telephone.
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Sure first question comes from the line of Michael from Jefferies. Please go ahead.
Hi, Good morning, Thanks, guys and congrats Tony on the new role looking forward to dish.
Maybe two questions for.
A young on 015, you might think that cohort three would be the group you could see the greatest effect given that much youngest patience, but in that group. You also see a lot of improvement with Richmond, Russia, and the Cherish study show maybe you could just delineate how you think about a three point improvement.
In cohort three versus cohort one and two in other words, how do you delineate.
Your expectations between those groups and then on wanting one and TGF beta are you.
Expecting you could actually see responses, even at low doses unit dose escalation and data that we're going to see later this year. Thank you so much.
Hi, Mike Yeah. So so starting with your first question about thinking about.
Just starting a efficacy in the content for the various cohorts for yes of course, one and two certainly a patient age 85 and older.
We are starting to source age five an older. The primary evidence indicates that the background expectation would be that its disease stabilization right motorfist stabilization resident absolute gains. So what we're going to look where there is for mean change from baseline to indicate that absolute improvement in motor function residences airplane change in that context, but he analysis there.
Well be to see what proportion of patients achieve at least the three point improvement from baseline.
Again, given that data from the phase three trials and its nursing as well as now risk the plan, it's rare to see a individual patients achieved.
Well improvements such as what the 15% in the cherished trial. So we think would be exciting if a substantial portion of patients and essar came on five.
A three point of greater improvement from baseline and will not be consistent otherwise like of course now for core three as you point out patients who they are started on the person in the age a young age <unk> 0.85, they do see some improvements over baseline it's not just motor function stabilization. So what we're looking for there.
Is to see a substantial improvements in motor function above what you when my generally observed with listeners in both in terms of the amount as well as overtime right because there's data now, indicating just the trajectory of what that curve looks like in terms of and proven our nursing isn't it's not like this dramatic improvement.
I'd like just.
This is very rapid there's a steady improvements you can just track on that.
In addition, a key part of this Coordthree analysis is we're doing some dose exploration right. We're looking to see if that those low dose army offer efficacy too.
As well as a high dose arm and then we'll see if there's any differentiation between the two arm such as in the time course effect, which can inform the dosing trends in the future and finally, we're going to look for effect. Upon other outcome measures such as that rise up from a module and the who motor milestone as a reminder, on the who motor milestones side, that's a very high bar to see efficacy.
Even in the Nusinersen Cherish study they did not show Nick improvement in fact, some of whom are milestones and approximately only 20% achieved a one a one milestone gains. So I think there's a variety of different ways a in coordthree to value for therapeutic effects from circadian five on top of listeners.
With regards to your question, Mike about looking for efficacy in the context of.
Dose escalation I think our base assumption is that it's really part b, where we're really going to explore a for the efficacy potential of combining essar came on at one.
With checkpoint inhibitors.
Again, the advantage that was we're looking at multiple different tumor types.
Sizable numbers, we're looking at population where patients have experienced primary check when you have resistance. So now in combination of you start seeing efficacy or even relative small numbers, it's exciting record each patient will not be expected to otherwise have.
A clinical response given the prior history of checkpoint never to resistance. So we'd be excited from that now with part a yeah. I mean, we are going to look and explore for potential efficacy. This would be more of a an upside pleasant surprise.
I think but the the advantages we do have the opportunity to take a look to see if it's possible right because like in party to the pot. This study population there are patients who try to checkpoint inhibitor Didnt have response and now we can see what happened in combination, but again, a big expectations really a part b is where we're going to look for efficacy signals.
Uh huh.
But again as well as you know in oncology, we're just going to continue to track and.
See what happens in dose escalation.
Okay, great. Thanks.
Thank you on next question comes from do Kim from BMO Capital. Please go ahead.
Hi, This is Jim soon on for Joe Thanks for the update and congrats on all the progress to on 181 from US first one for young could you elaborate a little bit more on expectations for us on that data that will be presented by year on omni amount of patient type of Biomarkers and how we should interpret that as central read through for the full read out in 2020.
One and then the second question for Tony maybe giving up the 181 study is targeting a wide variety of tumor type significantly large opportunity and that checkpoint resistant market could you tell your thoughts on the commercial strategy and how you see the program being developed going forward. Thanks.
Yes, so for the first question on the update on does cushion. So yeah. So so in the fourth quarter, a we're anticipating for any update on progress and dose escalation. So in other words, how far along with gotten.
And it doesn't selection process and I'm, obviously that include making sure that there is no major safety signals that would limit dosing.
In terms of a one thing I should point out is we do anticipate given the progress we've been observing today that we will be starting the combo dose escalation part eight to this quarter a party one in a two as a reminder, staggered and so we anticipate frying some updates where we stand at doses close in fourth quarter.
Heading towards that goal of initiating a part being the first quarter of next year I'm with.
Expectations as being a sourcing clinical response and safety data and 2021.
Thanks, James This is Tony so on commercial strategy, I mean look what should be clear task.
Is the drag on trial and whats ahead of us we'd need to group because you're having said that or thinking is that this drug me if it performs as we think it could.
Could be a backbone therapy. There is reasonably you could use it across multiple checkpoint inhibitors will obviously be explore a good news that across multiple tumor types.
So that's an exciting set of possibilities you could start as or things like you started the primary resistance is there a chance to expand the trick either et cetera could take you to add things across different tumor types. So there's potentially a big exciting development plan here.
With really no.
No set of commercial possibilities attached to that but you know job one is to get dragged it started to get some of this efficacy, but we're thinking about it at a very big way.
Great. Thanks, and congrats again, all the progress looking for to for data read outs.
Thank you.
Thank you I'm next question comes from the line of Kumar from Baird. Please go ahead.
Yeah that you're taking our question. So there was like in a big picture question about as our K 181. So you have these dose escalation and the dose expansion cohorts. So kind of a big question. Tony is how far do you go with wanting.
On your own versus kind of looking for a collaboration or partner to kind of more broadly really tests. This drug and this gives you a bit inhibition and they kind of broader array of Io combination studies.
Yes. Thank you. Good question. So walk oncology is a big space as I just laid out there's a potential for this is a very big drug.
Out of.
Ways to take it in clinical development, we would certainly be open to partnering in development.
On the product is I think one naturally would be given the potential size. It this is helping and get better that the oncology spaces look as all question that thing, obviously, which is you ought to engage in those discussions roll position of strength I think we have a task ahead of us. It we have some funds to do it to the as a value it gets a proof of concept.
So, we'll certainly consider partnering and but lot of people you. It's actually this is there a lot of big players in this space in a lot of people interested in what we're doing because it could be enabling so the whole checkpoint.
A check effort so very open to that but the question is the right time I think our first there is to generate some more data and strengthen our strength in our hands.
Okay, and then more micro question on one and one so to go to part eight to this quarter.
Is that decision based on kind of just safety data you've seen from the monotherapy dose escalation needed based upon safety and PK data as kind of like reached a PK, where you think are starting to see.
Drug exposure is that you would do it makes sense to combine with PD one they can get tease out what is the.
How do their thing, though the dose escalation of 82, given what you might have no seen so far and anyone from Dragon.
Oh, yes, so so just taking a step back so I think the way we've designed the they selected the doses was informed by where we believe based upon modeling and the preclinical data about where we anticipate feed that potential therapeutic effect range would be a pompous. It's true and then making sure that we had Doug drug coverage above that I just.
Vice additional buffer.
And so that will the way we approached it is now you are going through party wanted staggered party to want to make sure that theres.
Dose limiting toxicity challenges that would preclude us from escalation so it's probably a safety driven.
Decision, making process and so then as you progress along.
We'll be evaluating all the other parameters of course like Teekay.
Well biomarker, but the primary thing in terms of making dose escalation decisions driven by safety, because we're trying to push the dose.
To get it done at highest we can because until prevent otherwise we want to carry the highest dose forward and make sure that we're well into the therapy grant that we hypothesize could lead to the effects, we hope to see.
Yeah, and then 015 in the healthy volunteers city can you remind us did healthy volunteers seem also girls on my assignment image inhibition therapy kind of think led the genetic semis that a lot. So did you see any change in muscle mass and those of the volunteers.
Oh it held together so our focus.
For the phase one trials was phase two is actually on motor function, particularly fast which fiber function. So it wasn't that wasn't enough focus of ours. So I think the key thing here is remember as opposed to say rodents humans have a much more mixed balance a proportion of fast which in slippage fibers and given that that might then I had the preferential second fast food.
Fibers, you know that you can imagine a muscle individual muscle, which is most of the mix you got back the basket fiber, but then they wouldn't be <unk> no effect in the slippage fibers are minimal effect it'd be hard to detect something so yes, while they're picking the folks who have focused on that our focus really on a fast rifiber function that really is why we're excited about the SDMA hypothesis.
Yes, and the potential enough to make events or the prominent contribution of faster fiber atrophy fiber destination mechanism action. That's why we think really makes sense to evaluate thats or came on five to see if we can drive passed with fiber function improvement that we will measure directly.
Through the Hammersmith scale and other clinically meaningful outcome measures to see if our thoughts is true.
Okay, and then one last one about Oh on five so given the preclinical data you have combining <unk> SDMA mouse models with an estimated modulator.
Do you think six months will be enough time for my ascend inhibition to improve motor function and do you think you'll get greater improvement. The 12 month versus six months like are you thinking with the kinetics of my said inhibition and pretty motor function.
Yeah. So this is a 12 month study right.
But with that said it.
It is quite biologically plausible inconceivable that we may see therapeutic effects at six months.
And so given you know preclinical we do observe effects.
In short short course of time.
With treatment and so certainly because of that we want to investigate the potential that's okay me on five may have benefits.
At the six month time points. So that's why we're doing the incrementals to see or do we see the expects at that time point, but as you point out is it is a 12 month site. So we intend to carry important too.
Okay, great. Thanks.
Thank you.
Our next question comes from the line of David Marin Garden from Wedbush Securities. Please go ahead.
Thanks for taking my question.
On the patients who have completed the 12 month treatment period for one five topaz.
Could you.
Tell us how many were a monotherapy patients or and I believe that would be cohort, one and and monotherapy.
Thanks.
Oh, yes, so we haven't broken out just in terms of where those.
Patients are but I think at a high level I think there have been eight patients who have completed a the 12 month treatment period and all eight have opted in to continue forward.
Obviously, it's early in the rollover opportunities for extension for billions extension, but we certainly are encouraged that today than it continues the good patient engagement as all clinical trial investigator site engagement across the whole study.
Alright. Thanks.
Thank you.
As a reminder to ask a question you would need to press star one on your telephone to which are your question. Please press the pound key.
I show next question comes from the line of Marc Frahm from Cowen and company. Please go ahead.
Hi, Thanks for taking my questions and congratulations on all the new roles across steam.
Maybe just.
Looking back on the Dragon updates to be clear on what to expect it just isn't going to be spoke certain kinds enrollment status or are you also likely to share.
Whatever data you do have already on on the PD markers and such as well.
Sorry, so, yes, I assume you're referring to the fourth quarter update.
Yes, so so in terms of the fourth quarter private focus is just said to the upfront enough data, where we stand in terms of just a question how far we've advanced both in apart a one part to and obviously as part of that you know, we just to make sure that Theres no major safety signals right.
And then as part of you know as we continue to go through justification. We do we will look at peak pay and we are exploring various biomarkers.
So certainly we will be exploring that as well now in terms of.
In terms of where we might anticipate.
Efficacy data our expectation is that that's going to be more of a 2021 event like as we talked about earlier, our base assumptions that related part b that will really interrogate efficacy.
Now is there upside potential.
From the dose escalation sure, yes, and certainly we will be.
We set up the study for that we have the potential detect and early after a single, but the dart base assumption is that really part b that we'll be looking for the efficacy and that's it yes.
Okay, great. Thanks very helpful.
And then I'm thinking about the Topaz update.
The before the end of the year I guess, you're one of the therapeutic goals. You listed was you had this having a substantial portion of patients get a three point increase on the various skills.
I guess, you can get a little bit more granularity there. So what you define as substantial I mean are weak.
10, 20% of patients getting that or are we talking about more like 50%.
Getting to that level.
Yeah, Yeah. So I think you know again, there's two ways. We're looking at it right for both corresponding to one is looking for meaning for basically right given.
The natural history data that's available the data for nursing Harrison of patients who are age five and older at the time of initiation and now there's risk the fund data using a different endpoint.
With the MF and 32 as well as they took on the fee at all consistent observation that patients were started nusinersen age five an older on the private better pays more motor function stabilization rather than us improvements. Our goal here is to see if we have a mean change.
Baselines and shows excellent drew renters in zero point Stabilizations, we're really looking for the improvement now as far as you point out there is a key analysis here, which to look at what subset of patients what percentage patients are able to achieve at least at three point improve baseline and provide a little more context around that I remember that from the cherish study right for patients who are starting nurses.
At the age of five an older.
It was rare to see anyone achieved in fact, it was less than 15% and so we're looking for is a substantial proportion the.
Comfortably north of that too.
Because we believe that would be very exciting right because.
That would not be expected given the otherwise course above.
The even in setting of listeners driven.
Okay. Thank you.
Thank you.
Showing no further questions in the queue at this time.
I'd like to turn the call over to Mr., Tony King President and CEO for closing comments.
Good thanks, all for joining exciting Zionts, we're moving fast we've got a lot of data potentially coming out. The next stamkos order. So we're going to get back to work and.
Pursue our destiny. Thank you guys for joining me this morning forward.
Yes.
Thank you, Sir ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.
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