Q3 2023 Shattuck Labs Inc Earnings Call
[music].
Speaker 1: Good morning and welcome to the Sheddick Labs 3rd quarter, 2023 earnings conference call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. We'll now turn the call over to your host, Connor Richardson, Vice President of Investor Relations at Sheddick Labs. Connor, please go ahead.
Good morning, and welcome to the Fedex Labs third quarter 2023 earnings Conference call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time as a reminder, this conference call is being recorded I will now turn the call over to your host cornered Richardson Vice President of Investor Relations.
I should have Collabs Conor. Please go ahead.
Speaker 2: Thank you, operator. Good morning, everyone, and welcome to the Shatic Labs Conference call, regarding our third quarter, 2023 financial results, and recent business updates.
Thank you operator.
Morning, everyone and welcome to the shot at Glass conference call regarding our third quarter 2023 financial results and recent business updates.
Speaker 2: The press release reporting our financial results was issued pre-market this morning. And can be found on the Investor Relations section of our website, Shadiglabs.com.
The press release reporting our financial results was issued pre market. This morning, and can be found on the Investor Relations section of our website shattered glass dot com.
Speaker 2: During this morning's call, the Shatic Leadership Team will provide a business overview of the third quarter of 2023, including clinical development updates.
During this morning's call the Shaddock leadership team will provide a business overview.
Third quarter 2023, including clinical development updates speaking on today's call will be our Chief Executive Officer, and scientific co founder Dr. Taylor Schreiber, our Chief Medical Officer, Dr. Giovanni <unk>, and our Chief Financial Officer, Mr. Andrew Neil.
Speaker 2: Speaking on today's call, we'll be our Chief Executive Officer and Scientific Co-Founder, Dr. Taylor Schreiber, our Chief Medical Officer, Dr. Linnie Pendee, and our Chief Financial Officer, Mr. Andrew Neil.
We will then open the call for questions following our prepared remarks.
Before we begin.
To remind you that today's webcast contains forward looking statements within the meaning of safe Harbor provisions of the private Securities Litigation Reform Act of 1995.
Speaker 2: such statements represent management's judgment as of today, and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these states.
Such statements represent managements judgment as of today and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements for more information on these risks and uncertainties. Please refer to our most recent quarterly reports.
Speaker 2: For more information on these risks and uncertainties, please refer to our most recent quarterly reports on Form 10Q for the quarter ended September 30th, 2023, and our other filings with the SEC, which are available from the SEC's website, or on our corporate website, Shadoklabs.com.
On Form 10-Q for the quarter ended September 32023, and our other filings with the SEC, which are available from the Sec's website or on our corporate website Shattuck labs dot com.
Speaker 2: Any forward-looking statements represent our views as of today, November 9, 2020.
Any forward looking statements represent our views as of today November nine 2023.
Speaker 2: With that, I will now turn the call over to Dr. Schreiber, our Chief Executive Officer.
With that I will now turn the call over to Dr. Schreiber, Our Chief Executive Officer Taylor.
Speaker 3: Thank you, Connor. Good morning, everyone, and thank you for joining us today.
Thank you Conor and good morning, everyone and thank you for joining us today.
Speaker 3: We are very pleased that our lead clinical stage product candidate, SL172154, has advanced to a stage where we are able to begin sharing clinical data from both our hematologic and solid tumor program.
We are very pleased that our lead clinical stage product candidate <unk> 170, 154 has advanced to a stage, where we are able to begin sharing clinical data from both our hematologic and solid tumor programs.
Speaker 3: Importantly, we are also pleased to have observed our first responses and efficacy data across our clinical trials, including our Phase 1B clinical trial and platinum-resistant ovarian cancer, and our Phase 1AB clinical trial and acute myeloid leukemia, or high-risk myelotusblastic syndromes. We look forward to providing more detail.
Importantly, we are also pleased to have observed our first responses and efficacy data across our clinical trials.
<unk>, our phase <unk> clinical trial in platinum resistant ovarian cancer, and our phase <unk> clinical trial in acute myeloid leukemia or high risk Myelodysplastic syndromes, we look forward to providing more detail throughout the call.
Speaker 3: For the rest of the call, we will refer to SL172154 as 154.
For the rest of the call we will refer to as the one seven to 154 as 154.
Speaker 3: This morning we will discuss interim data from our phase 1B clinical trial of 154 in combination with pegalated liposomaldoxarubicin in patients with platinum resistant ovarian cancer.
This morning, we will discuss interim data from our phase <unk> clinical trial of 154 in combination with peg awaited life with thermal doxorubicin in patients with platinum resistant ovarian cancer.
Speaker 3: In addition, we will discuss the encouraging data from our ongoing phase 1A, B clinical trial in acute myeloid leukemia or higher risk myeloid dysplastic syndromes that was described in an abstract released last week and will be presented at the American Society of hematology annual meeting in early December .
In addition, we will discuss the encouraging data from our ongoing phase <unk> clinical trial in acute myeloid leukemia or higher risk Myelodysplastic syndromes that was described in an abstract released last week and will be presented at the American Society of Hematology annual meeting in early December.
Speaker 3: These data include dose escalation data for 154 as monotherapy and in combination with ASA cytodine in primarily relapse refractory AML and higher risk MDS patients. As a reminder, 154 is a dual-sided fusion protein.
These data include dose escalation data for 154 as monotherapy and in combination with Az's cytidine, and primarily relapsed refractory AML and higher risk Mds patients as a reminder, one five for the dual sided fusion protein.
Speaker 3: It inhibits the CD47 checkpoint receptor and also directly activates immune cells by CD40 engagement.
It inhibits the CD 47 checkpoint receptor and also directly activates immune cells by CD 40 engagement.
Speaker 3: The CD47 landscape has evolved significantly over the past 18 months.
The CD 47 landscape has evolved significantly over the past 18 months.
Speaker 3: Several advanced programs have encountered significant challenges with toxicity, including destructive anemia.
Several advanced programs have encountered significant challenges with toxicity, including destructive anemia.
Speaker 3: These safety issues and the related clinical challenges have led to significant skepticism regarding the potential clinical utility of the CD47 path.
These safety issues and the related clinical challenges have led to significant skepticism regarding the potential clinical utility of the CD 47 pathway.
We believe however that these safety issues are the result of the design of some CD 47 targeted agents and are not inherent to the CD 47 target itself.
Speaker 3: We believe however that these safety issues are the results of the design of some CD-47 targeted agents and are not inherent to the CD-47 target itself.
Speaker 3: We believe that conclusions currently being drawn regarding CD47 as a pathway should be confined only to specific individual ages.
We believe that conclusions currently being drawn regarding CD 47 is a pathway should be confined only to specific individual agents.
Speaker 3: We designed 154 to not engage FC Gamma receptors in order to avoid the anemias and other set opinions that have plagued other agents in the class.
We designed <unk> forward to not engage FC gamma receptors in order to avoid the anemias and other cytopenia as that have plagued other agents in the class.
Speaker 3: Earlier this year at ASCO, we shared clinical data from our phase 1A dose escalation clinical trial in platinum resistant ovarian cancer or PROC patient.
Earlier this year at <unk>, we shared clinical data from our phase <unk> dose escalation clinical trial in platinum resistant ovarian cancer or <unk> patients.
Speaker 3: That data demonstrated that 154 does not cause destructive anemia, and this observation remains true today.
That data demonstrated that <unk> does not cause destructive anemia, and this observation remains true today.
Speaker 3: we remain encouraged by the safety and tolerability profile of 154 to date.
We remain encouraged by the safety and Tolerability profile of 154 to date.
Speaker 3: 154 also differentiates from all other CD-47 inhibitors through a CD-40 agonist domain.
154 also differentiates from all other CD 47 inhibitors through its CD 40 agonists domain.
Speaker 3: This attribute of 154 has already led to a differentiated pharmacodynamic profile in dose escalation studies and may contribute to improved response rates, accelerated kinetics of response, and durability of responses in our ongoing clinical studies.
This attribute of $1 four has already led to a differentiated pharmacodynamic profile in dose escalation studies and may contribute to improved response rates accelerated kinetics of response and durability of responses in our ongoing clinical studies.
Speaker 3: In just a few moments, Dr. Linny Pandit, our chief medical officer, will expand on the encouraging data generated today.
And just a few moments Dr. Linda <unk>, our chief Medical Officer will expand on the encouraging data generated to date.
Speaker 3: At a high level, our confidence is bolstered by the interim results of 154 in combination with pegalated liposomaldoxarubicin, which we will call PLD in patients with proc.
At a high level, our confidence is bolstered by the interim results of one 504 in combination with Pegylate lysosomal doxorubicin, which we will call PLD in patients with <unk>.
Speaker 3: As of October 31st, 2023, we have observed an overall response rate of 27%, which if it holds, would exceed the PLD monotherapy benchmark response rate of 4% in the Pfizer-sponsored Javelin Ovarian 200 trial.
As of October 31, 2023, we have observed an overall response rate of 27%, which if it holds would exceed the PLD monotherapy benchmark response rate of 4% and the Pfizer sponsored javelin ovarian 200 trial.
Lenny will also highlight recent data from our phase <unk> clinical trial evaluating <unk> for both as monotherapy and in combination with <unk> decided deane in patients with relapsed refractory high risk Mds and AML.
We completed the dose escalation portion of this study in the second quarter of 2023, and these data will be presented at the upcoming Ash annual meeting in December.
We have initiated two different frontline dose expansion cohorts. We're 154 is being combined with <unk> decided in in patients with previously untreated higher risk Mds or <unk> 53 mutant AML.
We are very pleased with the momentum in this trial and enrollment has proceeded very quickly, which we attribute to the high unmet need for these patients and our investigators' enthusiasm regarding the differentiated profile of one 504.
We look forward to sharing an interim update from the frontline dose expansion cohorts in conjunction with Ash next month.
With that I will now turn the call over to Lenny who will dive into our clinical programs and provide an update on recent clinical data and activities.
Thanks, Dana and good morning, everyone 2022 continues to be a year of focused operational execution.
I am grateful for the relentless efforts of our team.
Participating investigators and most importantly, the patients themselves that have enabled this progress.
As Taylor outlined August 1st provide an update from our phase one b trial investigating <unk> in combination with DSD in patients with platinum resistant ovarian cancer and then provide some color on the data in last week's ash abstract from a phase one.
<unk> B trial investigating <unk> in combination with azacitidine in patients with AML and higher risk Mds.
Let's start with our ongoing phase <unk> combination clinical trials of <unk> in patients with platinum resistant ovarian cancer.
The data cutoff date of October 31st 2023.
16 patients with platinum resistant ovarian cancer have been enrolled into this study.
These patients have a median of one five prior lines of systemic therapy.
154, plus DSD had an acceptable safety profile, which was consistent with the safety profile of the individual agents.
Well one five for the most common drug related adverse event was infusion related reaction, mostly grade one or two.
As of the data cutoff date of October 31st 2023.
11 patients were evaluable for efficacy.
Seven three partial responses.
One confirmed partial response and two unconfirmed partial responses.
As of November nine 2023, both patients with confirmed partial responses are still on study and have not reached the date of confirmatory response assessment.
Four patients had a best response of stable disease and for patients had progressive disease.
As of the data cutoff date of October 31st 2023, and this is characteristics of the patients enrolled in this trial I assume you look at the characteristics of the patients enrolled in the <unk> sponsored javelin ovarian 200 trial, which is a recently published randomized trials that include <unk>.
Roll off.
In the javelin trial. The overall response rate for patients treated with DLD monotherapy was 4%.
Additionally to date.
Highest proportion of patients enrolled in our trial have bulky disease measuring over five C. N N danita and pretreatment with benefits of map all of which are poor prognostic factors.
Expect to complete enrollment of the expansion cohorts this quarter and to provide additional response and response durability data from the first cohort by midyear 2024.
Overall, we are encouraged by the emerging data from this combination cohort and look forward to update with more patients and longer follow up.
We are also continuing enrollment in our phase one trial of <unk> four in combination with Rituximab testing in platinum resistant ovarian cancer Andrew.
Enrollment and dosing are progressing quickly we expect to report initial combination data from this trial mid 2024.
Let us now turn to the progress we have made in our phase <unk> clinical trial in AML and higher risk Mds. In this trial, we are evaluating the safety Tolerability pharmacokinetics antitumor activity and Pharmacodynamic effects of 154, as both monotherapy and in combination.
<unk> the current standard of care.
At this time do not ash abstract 37 adult patients with primarily relapsed refractory AML or high risk Mds have received 154 as monotherapy or in combination with decitabine.
These patients had a median of two.
Prior lines of therapy.
There are 19 patients in the monotherapy cohort in 18 patients in the combination cohort as of the data cutoff date of May 25th.
2020 fleet.
In this trial wildfire, Paul had an acceptable safety profile as a monotherapy and in combination for one side for the most common drug related adverse event was infusion related reaction, mostly grade one or two.
Monotherapy responses have not been reported with CD 47 targeted agents in heavily pre treated relapse refractory AML patients.
Consequently, we were particularly encouraged by our monotherapy response in a heavily pre treated relapse refractory <unk> mutant AML patient.
This patient had a rapid response to fight for monotherapy achieved a morphologic leukemia free state and was subsequently taken to allogeneic transplant and remains leukemia fleet.
Additionally in other patients we also observed anti leukemic activity in the form of block count reductions.
We also enrolled several previous the untreated <unk> mutant high risk Mds patients in the dose escalation portion of our trial.
These data are included in the ash abstract.
The data cutoff date of July 10, 2023, antitumor activity was observed in combination with <unk> into a full <unk>.
Response, Evaluable patients with previously untreated <unk> mutant high risk Mds.
The offset to one complete response.
No treatment related <unk> 53, new high risk Mds patient, who remains on study and one complete response in a patient who has taken to bone marrow transplant.
Duke patients had best response of stable disease wonderful, let's take it to transplant.
Overall, we are encouraged by the growing body of data that validates the unique mechanism of action of one five Paul and instead of beauty potential to address the unmet needs of patients with AML at higher risk Mds.
Data continued to show evidence of CD 40, Cleveland Pharmacodynamic activity, both in peripheral blood and bone marrow.
Believes that CD 40 activation and the resulting environment.
Adaptive immune system is important in this team indications and may provide significant improvement to CD 47 blockade in terms of both the improved response rates and durability of response.
We look forward to presenting the complete data of the dose escalation portion of the trial in relapsed refractory patients at the Ash meeting and sharing initial data from the frontline expansion cohorts during a company sponsored event around the time of Ash next month.
With that I will now turn the call over to Mr. Neal to discuss our financial update Andrew.
Thank you Lindsey and good morning, everyone.
As Conor mentioned at the outset of the call the full financial results for the third quarter 2023 are available in our 10-Q and earnings press release filed pre market. This morning.
I would like to focus on a few key points from our disclosures.
We continue to be well positioned financially.
As of September 32023, our cash and cash equivalents and investments were $101 1 million.
In the third quarter of 2023, our research and development expenses were $24 $2 million as compared to $18 9 million for the third quarter of 2022.
In the third quarter of 2023, our general and administrative expenses were $5 1 million as compared to $6 6 million for the third quarter of 2022.
Our net loss for the third quarter of 2023 was 27 5 million or <unk> 65 per basic and diluted share as compared to a net loss of $24 $6 million or <unk> 58 per basic and diluted share for the third quarter of 2022.
Based on our current operating and development plans, we reiterate our financial guidance Shaddock believes its cash and cash equivalents and investments will be sufficient to fund its operations through year end 2024 beyond results from its phase one clinical trials of <unk> 107 to $1 four.
This cash runway guidance is based on our company's current operational plans and excludes any capital that may be received proceeds from any business development transactions and our additional costs associated with clinical development activities that may be undertaken.
With that I'll hand, the call back to Dr. <unk> for final comments Taylor.
Thank you Andrew.
In the third quarter of 2023, we made excellent progress across the four different ongoing expansion cohorts in our proxy AML and higher risk Mds trials.
We expect several additional milestones and clinical updates through the end of this year.
For data updates, we expect to first present complete data from the dose escalation portion of our phase <unk> clinical trial of one 504 in relapsed refractory AML and higher risk Mds patients at the 65th Ash annual meeting.
We also plan to present initial data from the frontline <unk> three mutant AML dose expansion cohort and the frontline higher risk Mds dose expansion cohort, combining 154, where they decided in in the fourth quarter of this year during our company sponsored event following ash.
For clinical program milestones, we expect to complete enrollment in the frontline higher risk Mds cohort in the fourth quarter of 2023.
We also plan to complete enrollment of our phase <unk> dose expansion cohort at one 504 in combination with PLD and product in the fourth quarter of this year.
Sure. The initial results gathered in our heme and solid tumor studies hold as the size and maturity of these cohorts increase 154 would have first to market potential among CD 47 agents and <unk> as well as both AML and higher risk Mds.
These are all areas of significant unmet medical need with multiple opportunities for accelerated development at subsequent registration directed studies taken.
Taken together I believe the combination of our experienced team transformational science and protein engineering as well as financial resources puts us in a strong position to move beyond our next set of milestones and into 2024.
Before we conclude today's call I would once again like to thank our patients and their families. The entire schaddick team, our investors and the many people who have been supportive along the way with that we're happy to take questions operator.
Thank you if you have a question. Please press star one on your telephone keypad, if you wish to remove yourself from the queue simply press star one again, one moment please.
For your first question.
Okay.
Yeah.
Your first question comes from the line of Jonathan Miller of Evercore ISI. Your line is open.
Alright, thanks, so much for taking the question guys and congrats on getting to some real clinical data here.
I'd love to start on the promise study and ask a little bit more detail about the baseline characteristics of these patients are obviously these are platinum resistant, but can you give a little bit more granularity on what other variety of agents. These patients have seen in their prior lines of therapy.
And then maybe a little bit more open ended.
As we think about.
Comping This program to other CD 47 programs, which obviously have a well has not been gathering the excitement that they once did.
What is your expectation for being able to demonstrate.
These patients that are responding the impact of CD 40 ligand outside of the molecule on the efficacy that you see.
Great. Good morning, John Thank you and thanks for the questions.
Lenny why don't you go ahead and answer Jon's first question around the baseline characteristics.
Of these patients and how they compare to javelin.
And then I'll follow you with the second part.
Yeah.
Thank you John for the question.
These patients compare very well to the patients.
And role in the Japanese study.
The majority of these patients and that's 88% of these patients had failed.
Frontline platinum containing regimen and were resistant to frontline platinum.
So 100% of these patients had received platinum a 56% of these patients had also received bevacizumab.
These patients have also received PARP inhibitors.
That's somebody isn't in the slide deck about patients have received pop as well.
Okay.
Okay.
Great. Thanks.
Yeah.
Pardon me.
With regard to how one four.
154 needs to show in these patients and how that compares to what's <unk>.
<unk>.
Hey man in higher risk Mds space with other cities 47 inhibitors.
As most of the audience probably knows this is Ben.
Evolving space over the last three years and.
Certain agents might have been discontinued and the AML and higher risk Mds space early on purely for competitive reasons under the assumption that <unk> would be first to market and therefore, the commercial opportunity might have dwindled.
Clearly that has changed and.
We certainly.
Look forward to gilead sharing more data around exactly what happened with enhanced and enhanced too.
As part of their new commitment to increase transparency.
It seems however, as though many of these patients enrolled to the Mac roll them out of arms.
May have discontinued earlier or may have had dose interruptions in a way that could have impacted the top line readout of that study.
And then hopefully we'll learn more about that.
Regardless.
154 has to stand on its own two feet.
Syndication and.
Clearly were encouraged by the differentiated safety profile the lack of destructive anemia.
And.
In preclinical models.
The activity of CD 40, agonism translated to both improved response rates and improved response durability and clearly in patients like this improved CR rates not just over the expectations of a decided in alone but over prior benchmarks with Asia plus drugs like MACRA.
<unk> are important to exceed.
And if and only if you exceed those CR rates. You then have an opportunity of seeing an improved duration of response.
An improved overall survival.
And so that's what we'll be looking to see.
Certainly share the first glimpse of that and proximity to ash in December.
And the higher risk Mds population, we're looking to exceed the Ada decided in benchmark in terms of complete response, which comes from the a previous study of about 22%.
By at least double.
And in terms of the P. P 53 mutant AML cohort.
He has decided in alone delivers complete response rates in the low single digits and the combination of ease of macro will get more data I hope soon but it seems to deliver CR rates in the low thirties and again, we'll look to exceed that.
By a substantial margin so.
These are things that we have to show on our own.
As the field hopefully learns more about them.
Other agents that have been discontinued.
Thank you. Your next question comes from the line of Joe Pat Goodness of Itchy runway. Your line is open.
Hey, everybody. Good morning, Thanks for taking the question than a nice to see the early data congrats as well so maybe Taylor wanted to see if we could get or do some scenario analysis here, maybe start with the AML Mds study what do you obviously the expansion cohorts need to read out but could you.
Envision a save more targeted path for initial approval say targeting T. P 53, or other focused mutation and then also can you provide any color with regard to the kinetics of the responses that you're starting to see in the AML Mds study.
Sure. Thanks for the question, Joe and good morning.
So as you know the one of the expansion cohorts is already specific to Tpa <unk> three mutant AML patients.
We're even in the frontline setting there is a very high unmet medical need.
And.
There certainly would be.
Opportunity for accelerating accelerated path there.
If we weren't a first hit the CR rate.
In excess of 40% or so I think that that would be interesting in and be a good indicator of what that could translate into in terms of duration of response.
Where we'll be looking to exceed something in the six to seven month range.
As a benchmark and.
Those are our readouts that we expect to come in the first half of next year, having fully enrolled that T. P 53 mutant AML cohort during the third quarter.
And would be the basis for discussion with regulators about.
First an incremental expansion of that study to confirm that risk that that data.
And subsequently what the registration directed path could be there, but I do agree that.
There is a potential accelerated opportunity.
In terms of the kinetics of response.
I can I can comment on a couple of data points that we have and we will certainly add to this soon.
The first of all that the relapsed refractory AML patient that is disclosed in the ash abstract.
As a monotherapy responder.
As linear outline this was a tough patient they have failed.
Seven plus three they failed flag failed then Asia.
And then they came on the study and had a response within the first cycle of one five for monotherapy.
That's unusual for a patient like this but it's consistent with.
The kinetics of response that we had observed with the preclinical equivalent of 154 and various models.
I can also say that the confirmed responder in Prague.
That response started at the very first eight week scan.
And that's also the case with the two unconfirmed responders and prop.
Whereas the first eight week scan they met the PR criteria. So yes.
It appears that the kinetics of response to one five for our rapid.
And that's helpful, especially when looking at.
Initial datasets and in trying to forecast how that might translate.
Great. Thanks Taylor.
Sure.
Your next question comes from the line of.
Mark a frame.
Frame of TD Cowen Your line is open.
Hi, Thanks for taking my questions and congrats on the the early response data today.
Maybe to start off with when when can you just explain the gap from the 16 who've seen dragging the 11, how many of those five.
Or still on trial.
Awaiting the first scan versus you know, having maybe discontinued for other reasons and that are you seeing any.
At the point of about half the patients have had PARP experience and perhaps not.
I know, it's small numbers, but any.
Any sense that maybe the efficacy is in one of those populations more than the other.
Great. Good morning, Mark. Thanks for the question, let me why don't you go ahead and take those.
Yeah.
Okay.
When he might be on mute.
Yeah.
Sorry, Mike.
Mark can you repeat the first question I lost the connection.
Oh I'm sorry, yes, the the safety database has 16 patients in it today and 11 or efficacy Evaluable can you just explain the kind of the five patient gap there how many of them are waiting for their first scan versus may be discontinued for other reasons.
On slide still on study they have they are waiting for their first scan.
Okay, and then of the responses you're seeing any sense that maybe this efficacy is more or less in the PARP experience versus non PARP eligible type of patient.
At the moment markets too early to kind of draw those conclusions.
The first patient had received the first patient.
Our had received <unk> inhibitors, the second patient.
And then next to patients.
U C bench, so it's hard to draw any conclusions at this time.
Okay. It makes sense and then thinking forward to next year when we'll see the initial.
Mirv combo data.
You know there there's a couple of different populations based on mirv expression level.
Fully expression levels.
Can you confirm how big of a dataset, you're expecting them to be able to provide in yeah.
And the robustness, you'll be able to look across those different expression levels.
Yes, we are expecting at UN drawn up to 70 patients.
That's how many patients will include high medium and low.
And we are working with immunogen to benchmark what would be an interesting response rate and durability of response in each of those subgroups.
Yeah.
Your next question comes from the line of Cadbury Tillman of BTG. Your line is open.
Oh, Hi, Thank you for taking my question I'm Christian a month's worth of area. So you actually answered part of my question was just about.
Your combo trial once you know what would you guys consider a meaningful or are like are.
Are you guys getting close to determining but considering that it is enrolling fully receptor alpha medium and low expresses.
But beyond that I noticed that it was years registration woodrow require 100% of the patients to receive prior bevacizumab.
Going forward are there plans to also make this requirement in that trial.
Great. Good morning, Christian Thanks for the question.
Let me why don't you go ahead and take that question as well.
Thank you for the question. So the trial was designed with the exact and eligibility criteria soraya.
So that all patients were required to have received bevacizumab and that's how the trial was written.
Got it thank you.
And my next question.
Oh.
P. O D. Combo trial are you guys planning to use biomarker analysis to determine differences in responders and non responders.
So what are you planning to use this to take all of these locations in the future.
Yes, Thanks Christian.
We are continuing to collect in a variety of different biomarker data from these patients.
Some of which is similar to the data that was shared in our <unk> abstract earlier this year with regard to.
Referrals cytokine responses Margination of city 40 expressing cells.
The changes in the immuno phenotype of both peripheral cells as well as through evaluation of pre and on treatment biopsies from these patients.
And we hope certainly that that data may inform.
Our patient selection strategy or a responder non responder analysis.
Subsequent date.
But well.
Report on that as the size of the dataset increases towards the end of the study.
Got it. Thank you that's helpful. Thanks for taking my question.
No problem.
Again, if you would like to ask a question. Please press star and the number one on your telephone keypad. Your next question comes from the line of Yugo.
No formal lists of Citi. Your line is open.
Yeah, Hi, Thanks for taking the question on <unk> I was just wondering if you plan to look at or if you already have looked at any correlation between the platinum free interval for these patients and the degree of response and then on on heme with respect to the frontline studies in <unk> 53.
High risk Mds, you have any reason to believe or biologic hypothesis that.
The 154 is a combo would be potentially more effective and one of these cohorts versus the other thank you.
Sure Good morning, Yigal, thanks for the questions.
As Lenny mentioned, 88% of the patients enrolled to date and the progress study.
Progressed within the first six months of of platinum and so this is.
No that's fair.
Fairly homogeneous.
Poor prognosis group with rapid kinetics of the disease.
And we really.
As Lenny alluded to before the size of the data set is not large enough where we can try to distinguish between.
Did it make a difference if the patient progressed on platinum within one to three versus three to six months.
Although we can say is that all of these patients were rapidly resistant to primary platinum.
Yeah.
And then with regard to.
Weather.
There is a difference in the sub populations or <unk> 53 million AML versus higher risk Mds in conjunction with a decided dean.
We're looking forward to sharing more data there soon.
With the frontline cohorts and.
What I can say is that.
It's always been a little bit of a.
A ministry why the Tpa <unk> three mutant AML patients with some prior studies.
Seem to do a bit better than the T. P 53, wild type patients because otherwise those are quite similar diseases.
And one of the hypotheses that it's been out there in the literature is that the.
The <unk> three mutant patients seem to have a higher mutational burden, perhaps there were more tumor infiltrating CDA positive T cells I E. Perhaps it was a more immunogenic tumor to start and then some of the T. P 53 wild type patients.
And part of the value proposition of adding a CD 40 agonist to a CD 47 inhibitor.
Was framed around the expectation that some of those characteristics might be normalized because of the immune activating potential of SR 40.
And so it's certainly something that we're looking at and you know a priori, we can't necessarily say that.
That would indeed be the case, but we'll we'll be sharing data soon and then following that.
Over the next six to nine months.
Okay. Thank you.
Welcome.
Okay.
And your next question comes from the line of Gil Blum of Needham <unk> Company. Your line is open.
Hey, good morning, and thanks for taking our question. So maybe just to focus here on the ovarian cancer, but would you gauge is a go no go decision on P. L D plus 154 and.
How relevant is the L. D. These days and truck I mean, you say some enrollment challenges here. So I'd love you to send here and I have a follow up.
Yes, good morning, gentlemen, thanks for the question.
I mean I can tell you that when we when we first started this study.
There were many investigators who only joined the study because of the law here arm because.
As is highlighted by the javelin study of PLD doesn't help very much.
These patients.
And you know.
It is now it took us about as long.
[noise] to enroll the first five patients in the study.
As it has to now complete this complete enrollment in this study.
And.
No.
Perceptions can can be changed by data right and.
I think we're starting to see that 154 is adding something in in both heme and solids and certainly.
People always seem to shy away from the word synergy and we can't say that quite yet, but if these data hold then that's what this will mean.
In the PLD setting.
This is an all comer population and a.
Our response rate in excess of 25% and an all comer product setting non biomarker selected.
In and of itself could be meaningful and could be very meaningful if it is accompanied by a duration of response that exceeds five months.
And so those are those are benchmarks that we will be looking toward.
As we are.
As the data mature over the first half of next year.
And similar to my comments on the <unk> three mutant AML cohort in terms of what the next step would be.
We'd be looking at an incremental expansion of the current study you know somewhere between adding 20 and 40 patients or so.
To confirm the results and two to enroll those patients with our current momentum.
And that would be the basis than have a regulatory discussion.
A discussion for the first registration directed study.
That's very helpful and my follow on is can we get a sense of the behavior of the non responding patients stable diseases kind of.
In immuno oncology or other times, you see at least per long staple diseases. Thank you.
Sure.
It's.
Too early to say too much as linear alluded to there were out of the balance of eight patients four had a best response of progressive disease in four and a best response of stable disease of varying lengths of time.
And I think we need to wait to see the full data set from the initial 20 patient cohort before we can make any assertions about.
Whether those patients with stable disease had stable disease for longer than you would expect.
In a patient population like this.
Alright excellent thanks for taking our questions. Thanks Bill.
Yeah.
Thank you. This concludes the Q&A session of the call at this time I would like to turn the call back over to Taylor Schreiber, Chief Executive Officer of should took labs for closing remarks.
Thank you operator, and thank you all for joining the Schaddick labs third quarter 2023 of the financial results and business update conference call. We appreciate your continued interest in Shattuck can we look forward to updating you on our milestones later this year. Thank you.
This concludes today's conference call. Thank you for participating participating you may now disconnect have a wonderful day.
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