Q4 2021 Curis Inc Earnings Call
Operator: Good afternoon, and welcome to Curis' fourth quarter and year-end 2021 earnings call. All participants will be in listen-only mode.
Good afternoon, and welcome to curious as fourth quarter and year end 2021 earnings call.
All participants will be in listen only mode should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.
Operator: Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press the star key, then 1 on your touchtone phone.
After the company's prepared remarks call participants will have an opportunity to ask questions.
To ask a question you May Press Star then one on your Touchtone phone to withdraw your question. Please press Star then two.
Please note this event is being recorded.
I would now like to turn the conference over to the company's Chief Financial Officer, and Chief Administrative Officer Bill Steinkrauss. Please go ahead.
Operator: To withdraw your question, please press star then 2. Please note, this event is being recorded. I would now like to turn the conference over to the company's Chief Financial Officer and Chief Administrative Officer, Bill Steinkrause. Please go ahead.
Thank you.
Bill Steinkrause: And welcome to Curis's fourth quarter and year-end 2020. Before we begin, I would encourage everyone to go to the investor section of our website at www.curis.com to find our fourth quarter and year-end 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially.
Welcome to curious as fourth quarter and year end 2000.
Before we begin I would encourage everyone to go to the investors section of our website at Www Dot curious dot com to find our fourth quarter and year end 2021 earnings release and related financial tables.
I would also like to remind everyone that during the call we will be making forward looking statements, which are based on our current expectations and beliefs.
These statements are subject to certain risk and uncertainties and actual results may differ materially.
For additional details please see our SEC filings.
Bill Steinkrause: For additional details, please see our SEC filing. Joining me on today's call are Jim Dentzer, President and Chief Executive Officer, and Bob Martell, Head of R&D. We will also be available for a question and answer period at the end of the call. I'd now like to turn the call over to Jim.
Joining me on today's call.
Are Jim Dentzer, President and Chief Executive Officer.
And Bob Martell head of R&D.
We will also be available for a question and answer period at the end of the call.
I'd now like to turn the call over to Jim Jim.
Bill good.
Jim Dentzer: Thanks, Bill. Good afternoon, everyone. It's my pleasure to welcome you to Curis's fourth quarter and year-end earnings call. At Curis, we are driven by our mission to develop the next generation of transformative cancer therapies that meaningfully improve and extend patients' lives. In the fourth quarter of 2021, we made significant strides towards that goal. To start, we're pleased to announce that our novel IRAC4 inhibitor, CA4948, will be adopting a new generic name, Emavucerteb, as well as introducing TAKE AIM, our brand name for clinical trials moving forward with Emma Hussertin. The Take-Aim branding was selected to highlight the targeted design of MMOs as the first-in-class IRAC4 inhibitor in oncology.
Good afternoon, everyone. It's my pleasure to welcome you to curious this fourth quarter and year end earnings call.
Jim Dentzer: As a reminder, Emma Vucertib is currently being evaluated in nine distinct patient populations across three clinical studies in AML, MDS, and B-cell cancers. The first study, taking leukemia, is a Phase 1-2 study with both monotherapy and combination arms, for patients with relapsed or refractory acute myeloid leukemia, or AML, and High Risk Myelodysplastic Syndrome, or M The second study, Take Aim Lymphoma, is a Phase I-II combination study with ibrutinib for patients with relapsed or refractory NHL or other hematologic malignancies.
Jim Dentzer: The third study is the Phase II Lucas study, evaluating Imivucertib in patients with lower risk MDS, being led by Dr. Uwe Platzbecker of the University of Leipzig in early January. We announced positive updated data from the Take Aim Leukemia Study in targeted patients with relapsed refractory AML or MDS whose disease is characterized by a spliceosome or FLT3 mutation.
A curious were driven by our mission to develop the next generation of transformative cancer therapies that meaningfully improve and extend patients' lives.
Jim Dentzer: The updated data set supported the findings presented at EHA last year, further demonstrating encouraging anti-cancer activity compared to standard of care therapies in an expanded set of patient data. As of December... We hit and rolled 49 patients in monotherapy, 13 of which had genetically defined diseases, either spliceosome mutation or FLT3 mutation, and were invaluable for efficacy.
In the fourth quarter of 2021, we made significant strides towards that goal.
Jim Dentzer: We plan to discuss data from this ongoing study with the FDA in the first half of this year with the goal of clarifying the regulatory path for bringing this novel therapy to patients in critical need. We will provide an update on that discussion later this year. Additionally, enrollment is proceeding well for the combination arm exploring amavucertib plus azacitidine for patients naive to HMA, and Emma Vucertib plus Phonetoclock for patients naive to Veneticlock.
To start we're pleased to announce that our novel Iraq for inhibitor CA 494, eight we'll be adopting a new generic name <unk> as.
As well as introducing take aim is our brand name for clinical trials moving forward with <unk>.
The taking branding was selected to highlight the targeted design.
As the first in class Iraq for inhibitor.
Oncology.
As a reminder.
<unk> is currently being evaluated in nine distinct patient populations.
Across three clinical studies in AML, Mds and B cell cancers.
The first study taking leukemia.
Is a phase one two study with both monotherapy and combination arms for patients with relapsed or refractory acute myeloid leukemia or AML.
And high risk Myelodysplastic syndromes or Mds.
The second study taking in lymphoma.
Is a phase <unk> combination study with ibrutinib for patients with relapsed or refractory NHL.
Other hematologic malignancies.
Jim Dentzer: We expect to have initial data from these combinations in the second half of this year. I'd like to briefly touch on the ongoing Phase 2 Lucas IST for patients with lower risk MDS being led by Dr. Uwe Platzbecker, the co-chairman of EHA's Scientific Working Group on MDS. Demonstration of safety and efficacy in low-risk MDS could lead to a potential breakthrough in the MDS field, while the current standard of care with EPO stimulating agents can be effective for patients with lower risk MDS who have low serum EPO. However, the effect is often transient. It is not disease-modifying, and it does not prevent the progression of MDS to AML.
The third study is the phase III Lucas study.
Evaluating <unk> in patients with lower risk Mds.
Being led by Dr. <unk> plots Becker of the University of Leipzig.
In early January .
Jim Dentzer: We believe that Emma Vucertib, with its direct targeting of IRAC-IV, could be a transformative disease-modifying alternative, allowing the potential to treat these patients in a much earlier stage of disease. Well, physicians can give leukemia patients transfusions, and they have drugs that can stimulate blood cell growth. At Curis, we're developing drugs that have the potential to stop the cancer. In these early days of clinical testing, our data have demonstrated the potential to do just that, even in patients with spliceosome mutations for whom existing therapies don't work.
We announced positive updated data.
From the take a leukemia study in targeted patients with relapsed refractory AML or Mds, whose disease is characterized by a spliceosome or flit three mutation.
The updated dataset supported the findings presented at Ehealth last year further demonstrating encouraging anticancer activity compared to standard of care therapies in an expanded set of patient data.
As of December .
We had enrolled 49 patients in monotherapy.
13 of which had genetically defined diseases, either spliceosome mutation or flit three mutation.
And were Evaluable for efficacy.
We plan to discuss data from this ongoing study with the FDA in the first half of this year with the goal of clarifying the regulatory path for bringing this novel therapy to patients in critical need.
We will provide an update on that discussion later this year.
Additionally.
Enrollment is proceeding well for the combination arm exploring <unk> plus is deciding for patients naive to HMA.
And <unk> plus the net of clocks, so patients naive to venetic clocks.
We expect to have initial data from these combinations in the second half of this year.
I'd like to briefly touch on the ongoing phase two Lucas I S. T for patients with lower risk Mds being led by Dr. Hubei Pops Becker the co chairman of <unk> scientific working group on Mds.
Demonstration of safety and efficacy in low risk Mds could lead to a potential breakthrough in the Mds field.
While the current standard of care with Epo stimulating agents can be effective for patients with lower risk Mds, who have low serum IPOH.
The effect is often transient.
It is not disease modifying.
And it does not prevent the progression of Mds to AML.
We believe that <unk> with its direct targeting of Iraq for <unk>.
Could be a transformative disease modifying alternative.
Allowing the potential to treat these patients in a much earlier stage of disease.
While physicians can give leukemia patients transfusions.
And they have drugs that can stimulate blood cell growth.
At <unk>, we are developing drugs that have potential to stop the cancer.
In these early days of clinical testing our data have demonstrated the potential to do just that even in patients with spliceosome mutation for whom existing therapies don't work.
Jim Dentzer: Now let's move on to our B-cell cancer program and the Take AIM lymphoma study. We initiated the combination study, evaluating Emma Vucertib with Ibrutinib last year after seeing clear efficacy with this novel monotherapy agent and seeing that the efficacy was durable over such an extended period of time for these extremely sick patients. The dose escalation portion of this study is expected to enroll approximately 18 patients in a 3 plus 3 design with emovucertib doses starting at 200 and escalating to 300 mg BID. Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype.
Now, let's move on to a b cell cancer program and the <unk> lymphoma study.
We initiated the combination study evaluating.
Evaluating <unk> with Ibrutinib last year.
After seeing clear efficacy with this novel monotherapy agent and seen that the efficacy was durable over such an extended period of time for these extremely sick patients.
The dose escalation portion of this study is expected to enroll approximately 18 patients in a three plus three design.
With <unk> doses, starting at 200, and escalating to 300 milligrams PID.
Ibrutinib dosing will be whatever is appropriate for the patients respective NHL subtypes.
Jim Dentzer: We expect to report initial data from this study in the first half of this year. Moving on to our second asset in the clinic, our first-in-class monoclonal anti-vista antibody, CI-8993, a novel immune checkpoint inhibitor we're developing in collaboration with Immunex for the treatment of patients with relapsed or refractory solid tumors. We were excited to present clinical data from our Phase I dose escalation study of CI8993 in January, demonstrating a promising safety profile and highlighting the potential of CI-8993 to activate multiple anti-cancer mechanisms.
We expect to report initial data from this study in the first half of this year.
Moving onto our second asset in the clinic, our first in class monoclonal anti Vista antibody Ci $89 93.
Jim Dentzer: CI-8993 is a monoclonal antibody designed to antagonize VISTA-mediated immune suppression through myeloid and T-cell mechanisms. We believe CI-8993 is the most advanced anti-VISTA antibody currently in clinical development and has the potential to be a game-changing cancer therapy. The role of VISTA may go beyond other checkpoint inhibitors, as we believe VISTA inhibition has the potential for broad application in many tumor types, both as monotherapy and in combination with existing checkpoint inhibitors. Because of VISTA's localization on a variety of immune cells, targeting it affects numerous cancer immune mechanisms, many of which are not addressed by targeting PD-1, CTLA-4, or other checkpoints.
Novel immune checkpoint inhibitor, we are developing in collaboration with <unk>.
For the treatment of patients with relapsed or refractory solid tumors.
We were excited to present clinical data on our phase one dose escalation study of Ci 80 993 in January demonstrating.
Demonstrating a promising safety profile and highlighting the potential of Ci $89 93 to activate multiple anticancer mechanisms.
Ci 80, 993 is a monoclonal antibody designed to antagonize the vista mediated immune suppression through myeloid and T cell mechanisms.
We believe Ci 80, 993 is the most advanced anti Vista antibody currently in clinical development and has the potential to be a game changing cancer therapy.
The role of Vista May go beyond other checkpoint inhibitors as we believe Vista inhibition has the potential for broad application in many tumor types, both in monotherapy and in combination with existing checkpoint inhibitors.
Because of this does localization on a variety of immune cells targeting it affects numerous cancer immune mechanisms many of which are not addressed by targeting PD, one <unk> four or other checkpoints.
Jim Dentzer: Our phase 1 dose escalation study has shown to date that CI8993 has a safe and well-tolerated safety profile. Initially, we started dosing at 0.15 mg per kg, which was the highest dose cleared in the Janssen study. We then escalated dosing to 0.3 mg per kg and most recently to 0.6 mg per kg. We were encouraged by our initial safety data as they appear to demonstrate the effectiveness of the procedures we implemented to manage expected CRS effects.
Our phase one dose escalation study has shown to date.
Hi, 80, 993 has a safe and well tolerated safety profile.
Initially we started dosing at one five milligrams per kilogram, which was the highest dose cleared in the Janssen study.
We then escalated dosing to 0.3 milligrams per kilogram and most recently to <unk> six milligrams per kilogram.
We're encouraged by our initial safety data as they appeared to demonstrate the effectiveness of the procedures, we implemented to manage expected Crs effect.
Jim Dentzer: The pharmacokinetic profile of CI8993 demonstrates the ability to overcome a PK sync effect and achieve meaningful drug exposure. This fact is exemplified by our observation of clear pharmacodynamic effects in CI-8993 with early signs that CI-8993 is activating multiple anti-cancer mechanisms in patients tested to date. For these reasons, we believe that therapeutic targeting Avista with CIA 8993 has the potential to be a critical addition to the immune oncology arsenal.
The pharmacokinetic profile of Ci 80, 993 demonstrates the ability to overcome a PK sink effect and achieved meaningfully meaningful drug exposure.
This fact as exemplified by our observation of clear Pharmacodynamic effects in Ci 80, 993 with early signs that Ci 80, 993 is activating multiple anticancer mechanisms in patients tested to date.
For these reasons, we believe that therapeutic targeting avista with CA $89 93.
Has the potential to be a critical addition to the immune oncology Arsenal.
Bill Steinkrause: We look forward to sharing more data on this in the second half of 2022. In summary... We're pleased with the progress we've made in 2021, and we look forward to further progress in 2022. With that, I'll turn the call over to Bill to review our financial results for the quarter. Thank you, Jim. Curis continues to operate from a place of financial strength. For the year ended December 31, 2021, Curis reported a net loss of $45.4 million, or $0.50 per share on both a basic and diluted basis, as compared to a net loss of $29.9 million, or $0.61 per share on both a basic and diluted basis, in 2020.
We look forward to sharing more data on this in the second half of 2022.
In summary.
We're pleased with the progress we've made in 2021 and we look forward further progress in 2022.
Bill Steinkrause: For the fourth quarter of 2021, Curis reported a net loss of $13.6 million, or 15 cents per share, on both a basic and diluted basis, as compared to a net loss of $7.5 million, or $0.11 per share, on both a basic and diluted basis for the same period in 2020.
With that I'll turn the call over to Bill to review our financial results for the quarter.
Thank you Jim.
<unk> continues to operate from a place of financial strength.
For the year ended December 31, 2021 curious reported a net loss of $45 million 4 million or <unk> 50 per share on both a basic and diluted basis as compared to a net loss of $29 9 million were <unk> 61 per share.
On both a basic and diluted basis in 2020.
For the fourth quarter of 2021, pure <unk> reported a net loss of $13 6 million or <unk> 15 per share on both a basic and diluted basis.
As compared to a net loss of $7 5 billion.
Or <unk> 11 per share on both a basic and diluted basis for the same period in 2020.
Bill Steinkrause: Revenees for the year ended December 31, 2021, or $10.6 million as compared to $10.8 million for the same period in 2020. Revenues for both periods comprise primarily of royalty revenues recorded on Genentech and Rocha's net sales of Airvage. Revenues for the fourth quarters of 2021 and 2020 were $3.1 million and $3 million, respectively. Operating expenses for the year ended December 31, 2021 were $52.7 million, as compared to $35.7 million for the same period in 2020. Operating expenses for the fourth quarter of 2021 were $15.7 million, as compared to $9.3 million for the same period in 2020, comprised of the following.
Revenues for the year ended December 31 2021.
Were $10 6 million as compared to $10 8 million for the same period in 2020.
Revenues for both periods comprised primarily of royalty revenues recorded on Genentech and Roche's net sales of <unk>.
Revenues for the fourth quarters of 2021 2020.
Our $3 $1 million.
$3 million respectively.
Operating expenses for the year ended December 31, 2021 were $52 7 million as compared to $35 7 million for the same period in 2020.
Operating expenses for the fourth quarter of 2021, $15 7 million as.
As compared to $9 3 million for the same period 2020.
I'm proud.
The following.
Bill Steinkrause: Cost of Royalty Revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche's AeroVegNet sales. $0.5 billion for the years and December 31, 2021 in 2020. Cost of royalty revenues of $0.2 million for 2021 and 2020. Research and development expenses were $34.9 million for the year ended December 31, 2021, as compared to $23.1 million for the same period in 2020. Development expenses were $10.8 million for the fourth quarter of 2021, as compared to $5.6 million for the same period in 2020.
Cost of royalty revenues, primarily amounts due to third party University patent licensed stores.
Connection with Genentech and Roche's <unk> sales.
$4 5 billion for the year ended December 31, 2021 and 2020.
Cost of royalty revenues.
$2 million.
Of 2021 and 2020.
Research and development expenses were $34 9 million for the year ended December 31, 2021, as compared to $23 $1 million for the same period 2020.
<unk> expenses were $10 8 million for the fourth quarter of 2021 as compared to $5 6 billion for the same period 2020.
Bill Steinkrause: This increase was primarily attributable to increased clinical and manufacturing costs for our programs and higher personnel spending as a result of additional headcount. General and administrative expenses were $17.3 million for the year ended December 31, 2021, as compared to $12.1 million for the same period in 2020. General and administrative expenses were $4.8 million for the fourth quarter of 2021, as compared to $3.5 million for the same period in 2020. The increase in general and administrative expenses was driven primarily by higher costs for stock-based compensation, professional consulting services, personnel, and insurance as compared to the prior year.
This increase was primarily attributable to increased clinical and manufacturing costs for our programs and higher personnel spending as a result of additional head count.
General and administrative expenses were $17 3 million for the year ended December 31, 2021, as compared to $12 1 million for the same period in 2020.
General and administrative expenses were $4 8 million for the fourth quarter of 2021 <unk>.
As compared to $3 5 million for the same period in 2020.
The increase in general and administrative expense was driven primarily by higher costs for stock based compensation.
Professional and consulting services personnel and insurance as compared to the prior year.
Net other expense was $3 4 million for the year ended December 31, 2021, as compared to $5 million with same period 2020.
Bill Steinkrause: $3.4 million for the year ended December 31, 2021, as compared to $5 million for the same period in 2020. For the fourth quarter of 2021 and 2020, net other expense was $1.1 million and $1.2 million, respectively. Net other expense primarily consisted of imputed interest expense related to royalty payments. As of December 31, 2021, Curis' cash, cash equivalents, and investments totaled $139.8 million, and there were approximately 91.6 million shares of common stock outstanding.
For the fourth quarter of 2021, and 2020 net other expense was $1 1 million and $1 $2 million respectively.
Net other expense primarily consisted of imputed interest expense related to royalty payments.
Yes.
As of December 31, 2021, curious as cash cash equivalents and investments totaled $139 8 million.
And there were approximately 91 6 million shares of common stock outstanding.
<unk> expects that its existing cash cash equivalents and investments should enable it to maintain its planned operations into 2024.
Operator: Curis expects that its existing cash, cash equivalents, and investments should enable it to maintain its planned operations into 2024. With that, I'd like to open the call for questions. Operator. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touch-tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys.
With that I'd like to open the call for questions operator.
We will now begin the question and answer session.
To ask a question you May Press Star then one on your Touchtone phone.
If you are using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
Operator: To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. The first question is from Alicia Young with Cantor Fitzgerald; please go ahead. Thanks for taking my question and congratulations on the progress that you guys have made over the past couple of months. I just wanted to drill a little bit down into maybe talking about how we're thinking about kind of the trial design, you know, what's really viable versus what might not be viable heading into the kind of...
At this time, we will pause momentarily to assemble our roster.
Yeah.
The first question is from Alethia young with Cantor Fitzgerald. Please go ahead.
Hey, guys. Thanks for taking my question and congrats on the <unk>.
Progress that you guys are making over the past couple of months.
Just wanted to drill down into.
And then maybe talking about how we're thinking about kind of the trial.
Trial designs.
What's really viable versus what might not be a viable heading into the kind of I know you have had this conversation with the FDA, but just how you're thinking about what the expectation and how you guys are framing that place to be.
Operator: I know you haven't had this conversation with the FDA, but just how you're thinking about what the expectation is or how you guys are framing up for what it should be on that front. And then I just also wanted to ask about VISTA, do you guys...
On that front and then I guess.
It's also going to ask.
Do you guys feel.
Alicia Young: I feel as if, you know, you will be in a position to potentially achieve proof of concept, you know, by the time we get to the end of the year. I mean, like, you'll kind of be past the safety and into, you know, kind of efficacious doses. And do you think – how do you think about kind of continuing monotherapy, or is there any kind of option that potentially does something more of a combination with this as well? Thank you, Alethea. Thanks for joining us as well.
As you know.
We'll be in a position to potentially achieve proof of concept by the time, we get to the end of the year.
Like you'll kind of be passive safety and <unk>.
Applications.
And do you think how do you think about kind of <unk>.
<unk> monotherapy or is there any option or potentially more.
The combination of that swap rates.
Thank you Alicia thanks for joining as well Bob you're probably the first the best person to talk to the trial design for <unk> and we can address the Vista one second.
Operator: Bob, you're probably the best person to talk about the trial design for 4948, and we can address the VISTA one in a second. Yeah. Hey, Alicia.
Bob Martell: Thanks for the question. So the trial design, you know, if we sort of break it down into high-risk MDS and AML, and I think, you know, currently, AML we believe is fairly straightforward. What we're trying to do is look both in parallel at a very rapid path to registration with the FDA, and that could involve a single-arm study looking at surrogate endpoints like CR and CRH. Those endpoints are validated by the FDA and used also in conjunction with durability of response.
Yeah, Hey, Alicia.
Thanks for the question.
The trial design.
We said in breaking down into high risk Mds, and AML and I think.
Currently the AML.
We believe is fairly straight forward, what we're trying to do is look both in parallel at a very rapid path to registration.
With the FDA.
And that could involve a single arm study looking at surrogate endpoints like VR and C. R. H those endpoints are.
Validated endpoints by the FDA and used also in conjunction with durability of response.
A couple of drugs.
Bob Martell: A couple of drugs have been approved in this space for AML, including Gilt-Rit Nib and Ivocide Nib, both with response rates in the low 20% range. So we think that this is a pretty viable approach, you know, and we also have a population here that, you know, historically has been quite challenging to get these types of responses, yet the, you know, in the data that we've presented so far, you know, we've presented a really very durable CR and CRH and quite good effects on the blood count for those patients in a very difficult-to-treat population.
Been approved in this space in AML.
Adding just written down.
And aside nib.
Both with response rates in the low 20% range. So we think that this is a pretty viable approach.
And we also have a population here.
Historically, it has been quite challenging to get these types of responses yet.
And the data that we presented so far.
We've presented.
It really very durable PR in CRH.
Great good effects on the blood counts are those patients in a very difficult to treat population.
Bob Martell: And so I think that's our main focus for the clinical trials for AML, and we'll discuss that with the FDA when we meet up. Yeah, thanks, Bob. So on the FISTA question, well, first, Alethea, does that answer your question on trial design for 4948? Yeah, that's helpful. I mean, I guess, you know, is there a distinction, though, in MDF, as to what you might do versus AML, which, I mean, obviously, I can see the kind of unmet need in the protocol, I mean, kind of how we've gone forward in AML, but with MDF, like, how do you kind of think about, you know, a later stage trial design that could have, you know, momentum there Yeah, so that's another population that is unique, although the historical evidence is that things don't work quite so well there.
And so I think that's our main focus for the clinical trial for AML, and we'll discuss that with the FDA coming up.
Yeah. Thanks, Bob So on the Fist question.
First our Lithia does that answer your question on trial design for 4948.
Yes.
Well I mean, I guess is there.
At this stage, though in Mds is the what you might see versus AML I mean, obviously.
I can see the kind of the unmet need in the protocol and then kind of going forward with them.
But how do you kind of think about.
Our later stage trial design that could have.
And then from there it will there is definitely multiple go ahead Bob.
Yes.
That's another population that is unique although the.
Historical evidence is that.
Things don't work so well there. So we have seen is clearly as you saw previously in that population.
Bob Martell: So we have seen clearly, as you saw previously, in that population, we've had very strong anti-cancer activity. So, for example, four out of six patients who had an elevated blast count at baseline normalized their blast count. So, striking anti-cancer activity.
We've had a very strong anti cancer activity. So for example.
Four out of the six patients who had elevated boss at baseline normalized with last call.
Striking anti cancer activity.
Bob Martell: And one of those patients even went on to a stem cell transplant, which is a potentially curative approach. So there we need to discuss with the FDA what type of surrogate might be optimal for this patient population. Clearly, inter-cancer activity is one endpoint that we'll discuss. Also, we'll be starting to think about our combination trials, and as those come in, that offers other opportunities for clinical trial development moving forward there. Yeah, maybe if I were to summarize that as well to emphasize a little bit of those, some of those points, Alit, yeah, I'd say that in AML.
And one of those patients even went on to stem cell transplant, which is a potentially curative.
So there we need to discuss with the FDA what type of <unk> might be.
Optimal for this patient population.
Clearly the anti cancer activity is is one endpoint that we will discuss.
Also we will be.
Certainly to think about our combination trials and as those come in and that offers other opportunities for clinical trial development moving forward there.
Yes, maybe if I were to summarize that as well to emphasize a little bit of those some of those points of Lithia I'd say that in AML.
Jim Dentzer: There's clarity on the endpoints that the FDA is going to want to see. To Bob's point, there are several drugs that have looked at the CR-H rate as an end point, and it was actually not just for accelerated approval; they got full approval on those endpoints. So, Gil's written them, I have a side name in it, in the side name, all about the CR-H rate.
There is clarity on the endpoints that the FDA is going to want to see to Bob's point.
There are several drugs that have looked at the CR cri rate as a as an endpoint and it was actually not just for accelerated approval. They got full approval on those endpoints. So it gets written them.
I decide in M&A in the siding them all.
C. RCRA trade. So there seems to be broad agreement on what sort of endpoints would make sense and there is broad agreement that our data look great and those endpoints compared to anything else used in relapsed refractory setting in.
In Mds.
In those same two points I'd say everybody.
Seems very comfortable that our data look terrific compared to what else gets used the lack of clarity is on what the endpoint is going to be and Thats, where theres a lot of discussion certainly we get a lot of questions about that because the fact of the matter is there are no drugs approved in relapsed refractory Mds.
Jim Dentzer: Certainly, we get a lot of questions about that because the fact of the matter is there are no drugs approved for relapsed refractory MDS. Given that there are no drugs approved, and there are no drugs approved because nothing's worked, it's not clear where the FDA will come out on that. So I think the AML path is, of course, much clearer. We just need to make that case to the FDA and get them comfortable that we're ready to go to the pivotal design stage on this.
Given that there are no drugs approved and there are no drugs approved because nothing has worked.
It's not clear where the FDA will come out on that so I think the ml path is of course much more clear we just need to go make that case to the FDA and get them comfortable that we're ready to go to the pivotal design on this but the endpoints are clear and our data look good on those endpoints in Mds are data look good certainly compared to.
Jim Dentzer: But the endpoints are clear, and our data look good on those endpoints. In MDS, our data look good, certainly compared to chemo, which gets used more than half the time in these patients. But the lack of clarity is simply because there are no drugs approved yet. So we will be trotting new ground with FDA on the primary endpoints in that study. Hopefully, that's helpful. No, that's very helpful. Okay. So maybe I will go to your VISTA question now.
Chemo, which gets used more than half the time in these patients.
But the the lack of clarity is simply because there are no drugs approved so we will be trading new ground.
With FDA on the primary endpoints in that study.
Hopefully that's helpful.
Very helpful. Okay great.
So maybe I will go to your Vista question. So yes.
Jim Dentzer: So yeah, so VISTA in 2021, the big check the box item was safe. We knew that CRS side effects were expected, and we designed the study to expect that and to manage them effectively. And so we needed to go out and prove that we could make it short, we could succeed, could we clear 0.15 mix per kick? And the answer was, we did, and we cleared 0.3, and we're now dosing at 0.6, so checking the box on safety so far has been a terrific win for 2021.
Yes, so <unk> in 2021, the big checked the box item was safety.
We knew that to expect Crs side effects. We designed the study to expect that and to manage them effectively and so we needed to go out and prove that we could to make it short we could succeed where janssen tail.
Could we clear 0.15 mix per kg and the answer was we did and.
And we cleared three and we're now dosing of <unk>. So the check the box on safety. So far has been a terrific win for 2021 and for 2022. The gold changes now we're on the hunt for efficacy.
We don't know exactly which dose level will lead to the type of concentrations of drug that will lead to tumor shrinkage, but that's what we're hunting for so we are looking to in mono therapy.
Dose.
Late and explore.
To try and find what is the right dose to expand on the exciting pharmacodynamic findings that we've seen so far and hopefully see evidence of tumor shrinkage at the same time. You mentioned are we are also thinking about combination therapy and the answer to that is yes.
Jim Dentzer: We will be moving forward and staying tuned to that discussion with an approach where we're going to study both monotherapy and combination therapy in the clinic in 2022. Just another question on low-risk MDS, what's the update there? I know it was an investigator's trial, but just kind of what's going on with that? I thought it was a pretty interesting trial. Yeah, it's a really interesting trial. As I mentioned in my comments, it's just because it's an IST, we don't have a whole lot of visibility into that.
We will be.
Moving forward and stay tuned on that discussion with an approach where we're going to study both monotherapy and combination therapy in the clinic in 2022.
And just a quick another question with Mckesson in low risk Mds.
Update there I know, it's an investigator trial, but just kind of what's going on with that I thought was pretty interesting trial.
It's a really interesting trial as I mentioned in my comments.
Jim Dentzer: My expectation is, I know that Dr. Plossbecker, who's, you know, he's the European lead in MDS, he's the head of the working group on MDS, he's got 17 sites in that study. So my hope is, and I say it's a hope, I can't promise, of course, since we don't run it, but my hope would be that we'll have But having a small molecule with our safety profile that's disease-modifying to use in that setting is something that obviously not just we're excited about, but obviously Dr. Plossbecker and his team are very excited about as well. So we look forward to hopefully seeing results from that study later this year. That's very helpful. Thank you very much. Thank you, Alethea.
It's just because it's in ISG, we don't have a whole lot of visibility to that.
My expectation is I know that Dr plots Becker, who is.
He is the European lead in Mds. He is the head of the Ehealth working group on Mds. He's got 17 sites in that study. So my hope is.
I'd say its a hope I can't promise of course since we don't run it but my hope would be that we'll have data from that study at some point this year, but having a small molecule with our safety profile that's disease modifying to use in that setting is something that obviously not just we're excited about but obviously Dr. <unk> and his team are very excited about as well. So we look forward.
Hopefully seeing.
From that study later this year.
At least that's very helpful. Thanks Yep. Thank you Ralph Thank you very much. Thank you Alicia.
Operator: The next question is from Ed White with H.C. Wainwright. Please go ahead. Good afternoon.
The next question is from Ed White with H C. Wainwright. Please go ahead.
Ed White: Thanks for taking my question. So just to dive down a little bit more into AML, as you said, you have clarity about the endpoints. How should we be thinking about the size of the study that you need?
Good afternoon, Thanks for taking my question.
Just to dive down a little bit more.
In AML as you said you have a clarity endpoint.
How should we be thinking about the size of the study that you need.
Ed White: and... You know, when you can start enrolling patients after you talk to the FDA, would you be able to start, you know, by the end of this year, or is it a next year event? And then, knowing what you know now about the pandemic, we've been dealing with it for two years, just wanted to get your thoughts on what you think enrollment trends could be. How fast could you get the trial involved?
And.
<unk>.
When we can start enrolling after you talk to the FDA would you be able to start.
By the end of this year or for the next year event and then knowing what you know now about the pandemic and dealing with it for two years.
Just wanted to get your thoughts on.
What you think enrollment trends could be how fast could you get the trial enrolled.
Jim Dentzer: Thanks. Okay, maybe I'll ask Bob to talk about the size of the study first. Yeah, so, you know, again, we can look at historical precedents in the studies that Jim and I mentioned that achieved approval with single-arm studies. They all enrolled somewhere between 100 and 200 patients.
Okay.
Maybe I'll ask Bob to talk about the size of the study.
First Bob.
Yes, so certainly again, we can we can.
And look at history historical precedence.
Studies.
Jim and I mentioned that achieved approval with single arm studies.
Hey.
All enrolled somewhere between 102 hundred patients.
Bob Martell: You know, given the very poor outcome in this population, we could explore even lower numbers, but, you know, probably somewhere in that range for a trial that could achieve approval. What we're hoping to do is, and we'll discuss this aspect with the FDA as well, in terms of study enrollment, consider potentially expanding our current trial, so patients that we've already enrolled into the trial will capture the data that would be relevant there, and then potentially continue enroll So those are a couple of options that we would discuss with the FDA.
Given the very poor outcome in this population.
We could explore even even lower numbers, but.
Probably somewhere in that range for a trial that could achieve approval.
What we're hoping to do here is we will discuss this aspect with the FDA as well in terms of the study enrollment.
<unk>.
Yeah.
Considering potentially expanding our current trial patients that we've already enrolled onto the trial.
We will capture the data yet.
I mean that would be relevant there and then continue to potentially enrolling that versus starting in your study. So those are a couple of options.
That we will discuss with the FDA.
Bob Martell: Yeah, and so, Ed, I would echo what Bob said, and especially when you look at the other studies that have been done historically, bear in mind that, you know, the survival once you're post-HMA in this setting is two to six months. Post-HMA specifically, the median survival is 2.3 months, which is crazy.
Yes.
So Ed I would.
Echo, what Bob said and especially when you look at the other studies that have been done historically bear in mind that the.
Its survival once your post HMA in this setting as is two to six months.
Posted post HMA, specifically median survival is two three months, which is crazy.
So we would expect that given the efficacy we've seen so far even though it's a small and so it's kind of hard to talk about powering the study for statistical purposes.
Jim Dentzer: So we would expect that given the efficacy we've seen so far, even though it's a small N, so it's kind of hard to talk about powering a study for statistical purposes, it seems reasonable to say that we would be in the range of other studies that have gone after a pivotal design in AML. Whether or not we can start in 2022 or 2023 is going to depend a little bit on the design that FDA accepts.
It seems reasonable to say that we would be in the range of of other studies that have gone after a pivotal design in AML.
Whether or not we can start in 2022 or 2023 is going to depend a little bit on the design that FDA access.
Of course, what we would hope for is a single arm study in which case.
Jim Dentzer: Of course, what we would hope for is a single-arm study, in which case, we're ready to go now. We've already been testing patients on single-arm studies, and so, of course, we would leverage those data and just keep steaming forward with the existing sites and recruiting from those and adding new ones. If, on the other hand, of course, the FDA comes back and says they want a controlled study, that's, you know, now you've got to get that protocol out, and now you're talking more of a 2023 start.
We're ready to go now.
Been testing patients on single arm and so of course, we would leverage those data and just keep steaming forward.
With the existing sites and recruiting from those and adding new ones.
If on the other hand of course, the FDA comes back and says they want a controlled study that's now <unk>.
<unk> got to get that protocol out and now you are talking more of a 2023 start but our hope would be that they will follow a precedent and go with a single arm study.
Jim Dentzer: But our hope would be that they'll follow precedent and go with a single-arm study. And then the last question you had about how fast it could enroll, you know; we've been really pleased at the rate of enrollment. I think it's the consequence of the unfortunate fact that survival is so grim for these patients. And the reason why survival is so grim is that nothing works. The number one genetic driver of disease in AML and MDS is IREC for Long Expression. And I think part of the reason why survival is so grim is that none of the treatments out there address that driver. 4948, now Emma Busurta, does.
And then the last question you had about how fast created role we've been really pleased at the rate of enrollment.
I think it's it's the consequence.
The unfortunate fact that survival. So grim for these patients and the reason why survival soak reminiscent nothing works.
The number one genetic driver of disease in AML and Mds.
Is Iraq for long expression.
And I think part of the reason why survival. So grim is that none of the treatments out there.
Address that driver.
4948, now and have restarted does so our hope would be that the excitement we've seen among the investigators so far would continue as we add more sites into the pivotal study.
Jim Dentzer: So our hope would be that the excitement we've seen among the investigators so far would continue as we add more sites to the pivotal study. Is that helpful, Ed? Yes, thank you, Jim. And just one last question on that regarding the discussion with the FDA. Do you have all the data in hand now to speak with the FDA that you want, or is there a reigning delay as you... are awaiting more? No, there's no delay.
Study.
Is that helpful.
Yes, Thanks, Kevin and just one last question on that.
Regarding the.
Discussion with the FDA you have all the data in hand now.
With the data with the FDA that you want or is for any delay.
Yes.
Our waiting more data.
Jim Dentzer: It is an ongoing study, so we're going to continue to have more data in hand with, you know, every day and week that progresses. I think our timeline is unchanged. We expect to have a discussion with FDA in Q2. That's what we're certainly going to ask for. We can't control when they schedule it, but we believe we'll have sufficient data to ask for that meeting, and we think it'll be a good discussion.
No.
Yes, Theres no delay it isn't ongoing study so we're going to continue to have more data in hand, with every day and week that progresses.
I think our timeline is unchanged we expect to.
Have a discussion with FDA in Q2, that's what we're certainly going to ask for it we can't control when the schedule it.
But we believe we will have sufficient data at task for that meeting and we think it'll be a good discussion but in terms of.
Jim Dentzer: In terms of, you know, how much data we have at any given point, the study is ongoing, so we continue to enroll patients through the process, and our hope would be, if it's a single-arm study, as we've been enrolling patients the whole time, we'll just keep adding those patients into the pivotal groups so that we can get to the NDA timeline that much more quickly. That would be our hope, of course.
<unk>.
How much data we have at any given point. The study is ongoing so we continue to enroll through the process and our hope would be if it's a single arm study as we have been enrolling patients the whole time.
We'll just keep adding those patients into the into the pivotal groups. So that we could get to the NDA timeline that much more quickly that would be our hope of course.
Jim Dentzer: Great. Thanks for taking my question. Sure. Thanks, Seth.
Great. Thanks for taking my question.
Sure. Thanks, Ed.
Operator: The next question is from Yale Jen with Laidlaw & Company. Please go ahead. Good afternoon, and thanks for taking my question. I'm just gonna add on the earlier question in terms of the FDA meetings. In terms of patients, do you see, by the time you talk to the FDA, do you have sufficient MDS patients versus AML patients? Or how do you see that?
The next question is from Yale Jen with Laidlaw <unk> Company. Please go ahead.
Yale Jen: And the second question to that is that what do you anticipate the ultimate sort of follow-up? The FDA will require you to assess the duration of response. Would that be roughly 12 months, whether that would be for the current study or for the future study? Yeah, so let me address the first one, and I'll ask Bob to talk to the second one in duration. Thanks, Yael, for calling in.
Good afternoon, and thanks for taking my questions I'm, just going to tackle on the first question in terms of the FDA meetings.
In terms of the patients do you see that by the time you talked to the FDA.
Fishing Mds versus AML patients or how do you see that in the second question to that is that what do you anticipate the ultimate total falloff FDA will require you to two to assess for the duration of response would that be roughly 12 months, but that will be for the current study or for us.
<unk> studies.
Yes, So let me address the first one and I'll ask Bob to talk to the second one in duration, thanks for calling in.
Jim Dentzer: So, about the number of patients for AML and MDS, in both cases, to be frank, the patient sample size is small. You know, we already made the data public in the first week of January. No matter how we slice it, we're gonna have a small data set when we go talk to FDA. Is that enough patients for FDA's purposes? We'll find out when we have the discussion. We think so.
No.
About the number of patients for AML and Mds.
In both cases to be Frank.
Patient sample size is small.
We already made the.
Data public in the first week of January .
No matter, how we slice it we're going to have a small data set when we go talk to FDA is that enough patients for fda's purposes, we'll find out when we had the discussion. We think so we think that the data are clear that the drug is active it's active as a single agent and it's active in a population where nothing else works.
Jim Dentzer: We think that the data are clear, that the drug is active, it's active as a single agent, and it's active in a population where nothing else works. I think that's a strong case to take to the FDA. Now, will we have more patients over time? Of course. That's exactly why we want to talk to them. We think this drug merits a pivotal study, and we're willing to put the resources to work to increase the number of patients to be able to demonstrate whether or not this really does merit approval. So that's the point of the discussion.
Jim Dentzer: Whether or not they differentiate how many patients we need for AML versus MDS is not clear. We'll find out over time. As I said in response to Alethea's question, I think the points that everyone agrees on are that there seems to be a really clear discussion point for AML. There's clarity in the end point, and there's clarity that our data look really good at that end point compared to existing therapies. In MDS, everybody's excited about how our data look compared to existing therapy, but there's not a whole lot of clarity on the endpoint. And so I think those will be the key items for discussion with FDA. Bob, could you answer the follow-up question on duration?
I think that's a strong fact pattern to take to the FDA now where we have more patients over time of course, that's exactly why we want to go talk to them. We think this drug merits pivotal a pivotal study and we're willing to put the resources to work to increase the patient size to be able to demonstrate whether or not this really does.
That approval so that's the point of the discussion.
Whether or not they differentiate how many patients we need for AML versus Mds, that's not clear we'll find out over time as I said in response to <unk> question I think.
Thank the points that everyone agrees on.
Our that there seems to be really clear.
<unk> discussion for AML, there's clarity in the endpoint.
And theres clarity that our data look really good in that endpoint compared to existing therapies.
In Mds everybody's excited about how our data look compared to existing therapy.
But theres not a whole lot of clarity on endpoint and so I think those will be the key items for discussion with FDA.
Bob could you answer the follow up on duration.
Bob Martell: Yeah, so I think what you're asking is how long after we enroll, you know, X number of patients do we need to wait to get the duration of response for the FDA, and So that really depends, ultimately, on the number of patients getting to a certain endpoint. And oftentimes, you know, in previous labels, the FDA has used kind of a six-month time frame for that, kind of looking for a certain number of patients to get beyond that point or to, you know, have an event such as progression.
Yes.
I think what Youre asking is how long after we enroll X number of patients do we need to wait.
To get the duration of response for the FDA.
So that really depends on ultimately the number of patients getting to a certain.
Certain endpoints.
And oftentimes the.
In previous.
Previous labels. The FDA is kind of a six months timeframe for that kind of looking for.
Certain number of patients to get get beyond that point.
Or to have an event such as progression. So we would we would monitor those patients.
Bob Martell: So, we would, you know, monitor those patients, and the total number of patients that we enroll may actually be large enough such that we, you know, hit that point even sooner than six months from the last patient enrolled. So, that'll be, ultimately, determined by our signals and the timing of the study. Okay, great. Maybe just one more question here regarding the VISTA. You started potentially starting the advocacy study later this year. It is that the human- and Bill Nye.
The total number of patients that we enroll may actually be large enough such that we hit that point, even sooner than that.
Six months in the last patients enrolled so that'll be ultimately.
Determined by our signal and the timing of the study.
Okay, Great maybe just one more question here regarding the risk charge.
Do you start potentially starting.
Efficacy study later on this year.
<unk>.
Is that the two of them.
So there is a high.
Yale Jen: Thank you. Thank you, co-tumor and any impact at this point, or you probably will take all comers. Yeah, actually.
Cold tumor.
The impact at this point or are you probably will take all comers.
Okay.
Excellent.
Bob Martell: Yeah, we definitely like to enrich the patient population. So, there are certain tumors that, you know, have a relatively high expression of VISTA. So, you know, in discussing with our investigators, we certainly encourage them to consider putting their patients that have those profiles into the study. So, for example, patients with mesothelioma have an extremely high expression of VISTA. Several gynecologic malignancies have an extremely high expression of VISTA, such as ovarian or uterine cancer.
Yes, we definitely like to enrich the patient population. So there is certain tumors that have relatively high expression of this stuff. So.
And discussing with our investigators we certainly encourage them to consider putting their patients that have those profiles onto the study. So for example patients with.
With mesothelioma.
Has extremely high expression of this.
Several of the gynecologic malignancies has extremely high expression of this stuff.
Ovarian or heater in cancer.
Bob Martell: Some types of non-small cell lung cancer and triple negative breast cancer also have very high levels of VISTA. You asked about hot versus cold, so certainly in our preclinical models, certain hot tumors are quite responsive to this drug. But also, we've had some clear evidence that, you know, this antibody or targeting this in general can overcome some of the issues. For example, bringing a cold tumor into a basically lowering the threshold for, you know, activation of the immune system, so perhaps bringing cold tumors into a hot tumor setting.
Some sense of non small cell lung cancer and triple negative breast also have very high levels of Vista.
And you asked Pete.
Versus call so certainly.
In our preclinical models certain hot tumors are quite responsive to this drug but also we've had some some clear evidence that.
This antibody are targeting Vista in general can overcome some of the issues for example, bringing a cold tumor into a.
Basically lowering the thresholds for.
Activation of the immune system, so perhaps screening colon tumors into a hot tumor setting.
Bob Martell: Okay, great. That's very... Go ahead. I'm sorry. Go ahead. The yellow...
Yes, Hi, Greg.
Well go ahead I'm sorry go ahead.
Bob Martell: I will add a little bit. Go ahead, Bob. Thank you. I'd say that in VISTA, to be fair, this is part of the challenge and also the exciting part of going after a novel target.
Yellow.
Little bit.
Go ahead Bob.
Please go ahead.
So I would add to that a little bit I would say that.
Investors to be fair. This is this is part of the challenge and also the exciting part of going after a novel target.
Jim Dentzer: We know that in the Cancer Genome Atlas, there are certain indications, as Bob mentioned, that are associated with high VISTA expression. They're clearly correlated with high VISTA expression. We don't know if it's correlation or causation. We're clearly going to try to enrich those patients for all the indications Bob mentioned, and hopefully, we'll see efficacy in monotherapy in those patients, but we don't know. That'll be part of the exploration.
We know that in the cancer genome Atlas there are certain indications as Bob mentioned that are associated with high Vista expression. There clearly correlated with high Vista expression, we don't know if its coral correlation of causation.
We are clearly going to try to enrich for those patients and all the indications Bob mentioned and hopefully we will see efficacy in monotherapy in those patients.
But we don't know that will be part of the exploration.
Jim Dentzer: Is VISTA a target where knocking it down in monotherapy is sufficient in certain indications? But we also want to pursue combination therapy. You've seen our preclinical data set, and it seems to be tremendously synergistic with PD-1 and CTLA-4, for all the reasons that the literature suggests. It's just never been tested in patients before. I think the...
Is this a target we're knocking it down in monotherapy is sufficient in certain indications.
But we also wanted to pursue combination therapy, you have seen our preclinical dataset and it seems to be tremendously synergistic with PD, one and <unk> four.
For all the reasons that the literature suggest it's just never been tested in patients before I think the.
Jim Dentzer: The idea that we are hitting the target and the target's having an effect is suggested not just by the CRS symptoms that we have seen but also by the PD data that we have published in patients. And I think as we increase drug concentrations both in monotherapy, in targeted indications, and also in combination, we hope to see that the findings that we saw in the lab show up in the clinic as well. But that's, as I say, that's part of the fun of pursuing a new target that no one's ever gone after before. So stay tuned. Thanks a lot, and please enjoy!
The idea that we are hitting the target and the targets having effect as suggested.
By not just the.
The Crs symptoms that we have seen but also by the PD data.
We have published in patients.
And I think as we increased drug concentrations, both in monotherapy and targeted patient in targeted indications and also in combination.
We hope to see that the findings that we saw in the lab show up in the clinic as well, but that's as I say, that's part of the funnel pursuing a new target that no one has ever gone after before so stay tuned.
Well, thanks, a lot and pacer enjoy it sure. Thanks Yale.
Operator: The next question is from Soumit Roy with Jones Trading. Please go ahead. Hi, this is Dania speaking on behalf of Soumit Roy.
The next question is from Smart ROI with Jones trading. Please go ahead.
Hi, This is Daniel let me try thank you for taking our questions and congrats on the update.
Dania: Thank you for taking our questions, and congratulations on the updates. I would first like to ask about the AML-MDS trial. Do you expect that with the clinical hold for the anti-CD47 agents? Are you expecting any specific uptakes from the MLMDS patients, especially for high-risk MDS? I'm sure so.
I would first like to ask about.
The AML Mds trial.
With a clear.
Alright.
700, <unk> are you expecting.
Uptick take from.
Then in Mds patients, especially for high risk Mds.
Jim Dentzer: I think the biggest issue with megrolimab going on hold is, Yeah, all things being equal, anybody else that's got a study going in AML and MDS, those patients need to go somewhere. So all other trials and studies would benefit from enrollment, all things being equal. I would think the bigger question for us when a physician considers which trial to go into is, "Is it a megrolimab combination study?".
Sure. So I think the biggest issue with Mcgraw.
Going on hold.
Yes, all things being equal anybody else Thats Thats got a study going in AML and Mds those patients need to go somewhere so all the all other trials in study would benefit.
And enrollment.
All things being equal.
I think the bigger question for us.
When a physician considers which trial to go into is it a mcgraw Mab combination study.
Jim Dentzer: or is it an emobucirtib combination study; they want to think about what's the best thing for patients. Now, there's clearly a larger data set for MacrolaMap than there is for Emma Viserte, but both patients were studied as monotherapies. And you may remember that the monotherapy data for McGilmab didn't look anywhere near as good as the monotherapy data for Emma Boussard. So, I think our conversations with the physicians are more about whether you're going to combine a drug with azacitidine. Which drug do you want to combine it with?
Or is it an MLP sorted combination study they want to think about what's the best thing for patients now.
Now, there's clearly a larger dataset from our gorilla math than there is for some of the circuit.
But both patients were studied in monotherapy.
And you may remember that the monotherapy data form of going that didn't look anywhere near as goods.
As the monotherapy data for <unk>.
So I think our conversations with the physicians.
Or more about if you're going to combine a drug with <unk>.
Which drug do you want to combine with.
Jim Dentzer: and we think we've got a pretty compelling case that this is a drug you want to choose in that case, is Emerald for certain, whether they're on clinical hold. So, all things being equal, I think that should help other drugs that are being studied in the face of competition, but I think for us in particular, having the only drug in the clinic that targets the driver of disease, or at least the largest driver of disease, is really the more important factor. And as for the 8993, will you be collecting baseline VISTA status? Are we going to see stratification in the next update, or expression levels? Yeah, actually, Bob, do you want to talk to him about that?
And we think we've got a pretty compelling case that your drug you want to choose in that case is for certain.
Whether they are on clinical hold or not.
So.
So, yes, all things being equal I think that should help other other drugs that are being studied in the face, but I think for us in particular, having the only drug in the clinic that targets the driver of disease or at least the largest driver of disease is really the more important factor.
Makes sense.
And as far as then.
893.
Would you be collecting baseline this does better and we're going to see.
Jason I.
I think next question level.
Yes, actually Bob do you want to talk to them.
Bob Martell: Yeah, we're capturing a lot, you know, a lot of aspects, including baseline information from patients. Although, to be clear, we're not selecting patients specifically for HIVISTA, but we'll be monitoring that and ultimately correlating that, as well as other, are appraised with. So, as you saw, some of the data that we presented in January, we have a pretty robust, you know, biological and pharmacodynamic program going on for that molecule. And we think that that's going to provide a great perspective on VISTA in general as a target, and in particular, that 8993 is an excellent agent there that has not only great PK exposure but, more importantly, in patients, we're already seeing really dramatic pharmacodynamic effects that really affect anti-cancer mechanisms directly.
Yes, we're capturing a lot.
A lot of aspects.
Including baseline information from patients although to be clear, we're not selecting patients specifically for high Vista, but we'll be monitoring that and ultimately correlating that as well.
Barclays.
So and you saw some of the data that we presented in January we have a pretty robust.
Biologic and Pharmacodynamic program going on for that molecule.
And thats going to work.
Provide a great perspective on this in general as a target and specific that <unk>. Three is an excellent agent there that that has not only great PK exposure, but more importantly in patients we're already seeing really dramatic pharmacodynamic effects.
It really affect anticancer mechanisms.
Bob Martell: So, you know, we're really excited about our pharmacodynamic and biological profile of this drug for our patients. Great, looking forward to the updates. Thank you. Thank you very much. Again, if you have a question..., there is then one. The next question is from Dane Leone with Raymond James. Please go ahead. Hi, guys. Thanks for taking the call. Um... Yeah, I just, uh... Any color you can
<unk>. So we're really excited about our our pharmacodynamic and biologic profile of this drug.
Patients.
Great looking forward to that thank you.
Thank you very much.
Again, if you have a question.
Then one day.
Next question is from Dane Leone with Raymond James. Please go ahead.
Hi, guys. Thanks for taking the question.
Yes.
Any color you can get in terms of how do you how you view the cadence.
Dane Leone: How do you view the cadence of enrollment, continued enrollment for 4948, and what that provides you with a line at the site for setting expectations for clinical updates on the SplicenZone cohort this year and then when we could get first data out to... Maybe the combination study, and just any color again, is the clinical hold on McGraw-Lamab. Thank you. Sure.
Enrollment.
Continuing enrollment for 4948 and what that.
Provide you with.
In terms of a line of sight for setting expectations for clinical updates on <unk>.
Despite them cohort this year.
Then when we could get first data out too.
Maybe the combination studies and just any color again on.
Yes.
The clinical hold on the Gorilla math Mike.
Accelerate potential enrollment in the combination studies with <unk>.
And what.
What are your general cadence of enrollment is expected or how that's been going so far thank you.
Jim Dentzer: Thanks, Dane, and thanks for joining the call. So I think my comments on Macrolomab and the impact of their clinical hold on our enrollment pace, I think I answered a few minutes ago. As I said, I think, all things being equal, the halt of the Macrolomab study should help us and anybody else that wants to run a clinical study in A&L and MDS. I think the bigger factor, though, for us versus Macrolomab is going to be what's best for the patient.
Sure Thanks, Dan and thanks for joining the call.
So I think my comments on <unk> and the impact on on their clinical hold on our enrollment pace I think I answered a few minutes ago.
As I said, I think all things being equal.
On the whole to be growing that study should help us and anybody else that wants to run a clinical study in AML and Mds I think the bigger factor, though for us versus Makola map is going to be what's best for the patient and if you have two studies to choose from as a clinician is an investigator.
Jim Dentzer: If you have two studies to choose from as a clinician, as an investigator, to combine azazitidine, which drug do you pick? Do you put them in a study that combines it with Macrolomab or a study that combines it with emohucertib, formerly known as 4948? I think we can make a very strong case. You want to put it in azacitin plus amilforcercin, based on the single-agent activity that we showed versus Macrolimab. But that said, I think you're right.
To combine with <unk> decided in which drug you picked you put them in the study that combines it with the <unk> study that combines it with <unk>.
Formerly 4948.
I think we can make a very strong case.
<unk>.
You want to put it in is us, adding plus and the surgeon.
Just on the single agent activity that we showed versus mozzarella, Matt, but that said I think you're right all things being equal to clinical hold should be should be helpful for us.
Jim Dentzer: All things being equal, the clinical hold should be helpful for us. We've seen a really exciting uptick in enrollment. You may remember that we had two spliceosome patients a year ago. We had three at EHA in June, and for the January update, we had 13.
<unk> seen a.
Really exciting uptake uptick in enrollment you may remember that we had two splices on patients a year ago, we had three at Ehealth at June .
And for the January update we had 13.
Jim Dentzer: So we're seeing a fairly dramatic uptick in physicians that are finding these patients and wanting to put them on our study. So my hope is that we can maintain that kind of excitement level and that we will be producing data that we can report out on later this year on a whole host of fronts. So we've got monotherapy data with spliceosome patients in AML, spliceosome patients in MDS, and FLIT3 patients in AML, and combination therapy data with emovucertib and azacitidine, and also emovucertib plus menedoclox.
We're seeing a fairly dramatic uptick.
Physicians that are finding these patients and wanting to put them onto our study. So my hope is that we can maintain that kind of excitement level.
And that we will be producing data that we can report out on later this year on a whole host of fronts. So.
So we've got monotherapy data with spliceosome patients in AML spliceosome patients in Mds flit three patients in AML combination therapy data with <unk> and is targeting also <unk> plus and <unk>, we've got the ISP.
Jim Dentzer: We've got the IST going in low-risk or lower-risk MDS, and we've also got data on combination with Evrutinib. So we've got a whole host of clinical activity going on simultaneously. And my hope is that we're going to have a raft of data across the board. And my hope would be, of course, that it will be just as exciting in 2022 as it was in 2021.
<unk>.
Going in low risk or lower risk Mds.
And we've also got combination with Ibrutinib data. So we've got a whole host of clinical activity going on simultaneously and my hope is that we're going to have a raft of data across the board and my hope would be of course that it will be just as exciting in 2022 as it was in 2021.
Jim Dentzer: Just one follow-up on that. So the, the, the, uh, Enrollment into the fan and Aether company cohorts are not, they're not- So that's an all-comers, regardless of mutational status. That's right, so they're all comers, but of course, what we would look to do is replicate the experience that we had preclinically, which was preclinical, we showed terrific synergy or at least a terrific additive effect in the patients who were going to go on azacitidine or venetoclox or the doublet, for that matter, preclinical in all three cases, the data were significantly more compelling when you So what we're looking to do in the clinic is replicate that.
Just one follow up on that can you.
So the.
Enrollment into the than in Asia.
Combination.
Cohorts or not.
They are not selected patients right.
All comers, regardless of mutational status.
That's right so theyre, all comers, but of course.
What we would look to do is replicate the experience that we had pre clinically.
Pre clinically we showed terrific synergy or at least terrific additive effect that the patients who were going to go on as decided in orbit EDA clocks or the doublet for that matter pre clinically in all three cases, the data were significantly more compelling when you added <unk> to it whether it was <unk>.
<unk> therapy is decided in monotherapy or the doublet. So what we're looking to do in the clinic is replicate that.
Jim Dentzer: We want to get combination with phonetoclax, combination with azazitidine, and then, assuming that that goes well, we'd love to pursue a triplet as well. And, uh... Can you give an update on just how many patients you've enrolled into the combination arm? We haven't given an update on that yet, but that will be part of the update that we give later this year.
We want to get combination with an <unk> combination with Azacitidine and then assuming that that goes well wed love to pursue a triplet as well.
And Scott.
Can you give an update on just how many patients you've enrolled into the combination arms.
I haven't given you haven't given an update on that yet but that will be part of the update that we're going to get later this year.
Okay.
Alright, thanks. Thank.
Thank you.
Operator: Thank you. This concludes our question and answer session. I would like to turn the conference back over to the company's President and Chief Executive Officer, James Dentzer, for any closing remarks. Thank you, Gary, and thank you, everyone, for participating in today's call. And, as always, thank you to the patients and families participating in our clinical trials, to our team at Curis for their hard work and commitment, and to our partners at Origin, Immunext, and the NCI for their ongoing help and support. We look forward to updating you again soon. Operator. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect. The Bulletproof Executive, 2013
This concludes our question and answer session I would like to turn the conference back over to the company's President and Chief Executive Officer, James Dentzer for any closing remarks. Thank.
Thank you Gary and thank you everyone for participating in today's call and as always thank you to the patients and families participating in our clinical trials to our team at <unk> for their hard work and commitment and to our partners at <unk> and the NCI for their ongoing help and support we look forward to updating you again soon.
Operator.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Yes.
[music].
Jim Dentzer: Now for 2022, the goal changes. Now we're on the hunt for efficacy. We don't know exactly which dose level will lead to the type of concentrations of drug that will lead to tumor shrinkage, but that's what we're hunting for. So we're looking to, in monotherapy, dose escalate and explore to try and find what is the right dose to expand on the exciting pharmacodynamic findings that we've seen so far and hopefully see evidence of tumor shrinkage. At the same time, you mentioned, you know, are we also thinking about combination therapy? And the answer to that is yes.
Jim Dentzer: So, there seems to be broad agreement on what sort of endpoints would make sense, and there's broad agreement that our data look great on those endpoints compared to anything else used in the relapse-reflective setting. In MDS, on those same two points, I'd say everybody seems very comfortable that our data look terrific compared to what else gets used. The lack of clarity is on what the end point is going to be, and that's where there's a lot of discussion.