Q4 2020 Curis Inc Earnings Call

Good afternoon, and welcome to curious as fourth quarter and year end 2020 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: Good afternoon, and welcome to Curis' fourth quarter and year-end 2020 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. After today's company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then 1 on your touchtone phone. To withdraw your question, please press star, then 2. And please note, this event is being recorded. I would now like to turn the conference call over to the company's Chief Financial Officer, Bill Steinkraus. Please go ahead.

After todays 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 call over to the company's Chief Financial Officer Bill Steinkrauss. Please go ahead.

Thank you.

Bill Steinkraus: Thank you, and welcome to Curis' fourth quarter and year-end 2020 earnings call. Before we begin, I would encourage everyone to go to the investor section of our website, www.curis.com, to find our fourth quarter 2020 earnings release and Related Financial Papers. I would also like to remind everyone that during the call, management will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially.

And welcome to curious as fourth quarter and year end 2020 earnings call.

Before we begin I would encourage everyone to go to the investors section of our website at Www Dot <unk> dot com to find our fourth quarter 2020 earnings release and related financial tables.

I would also like to remind everyone that during the call management will be making forward looking statements, which are based on our current expectations and beliefs.

Statements are subject to certain risks and uncertainties.

Actual results may differ materially.

For additional details please see our SEC filings.

Bill Steinkraus: 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, our 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.

Bob Martell.

Our 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.

Thank you Bill.

James E. Dentzer: Good afternoon, everyone, and thank you for joining us today. As ever, our mission at Curis is to develop the next generation of targeted cancer therapy to meaningfully improve and extend patients' lives. In that regard, 2020 was an especially constructive year for Curis, despite the difficulties of the ongoing COVID-19 pandemic. We were fortunate to be able to continue bringing our novel therapeutics to patients enrolled in our clinical studies and maintained a steady pace of progress throughout the clinical process, culminating in a number of exciting updates from our lead ass at CA4948, our first-in-class IRAC4 kinase inhibitor, released during the ASH annual meeting in December.

Good afternoon, everyone and thank you for joining us today.

As ever our mission ex curious is to develop the next generation of targeted cancer therapies to meaningfully improve and extend patients' lives.

In that regard 2020 wasn't especially constructive year for curious despite the difficulties of the ongoing COVID-19 pandemic.

We were fortunate to be able to continue bringing our novel therapeutics to patients enrolled in our clinical studies and maintained a steady pace of progress throughout the clinical process, culminating in a number of exciting updates from our lead asset CA 4948, our first in class Iraq for.

Kinase inhibitor released during the Ash annual meeting in December.

James E. Dentzer: Presently, our IRAC-IV platform is led by two ongoing clinical studies. One, in combination with the BTK inhibitor ibrutinib, for patients with relapsed or refractory non-Hodgkin's lymphoma, and the second, the 4948 Monotherapy Study, in patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS.

Presently.

<unk> core platform is led by two ongoing clinical studies.

One in combination with the BT K inhibitor ibrutinib for patients with relapsed or refractory non Hodgkin's lymphoma.

And the second 494, a monotherapy study.

In patients with relapsed or refractory acute myeloid leukemia, or AML and high risk myelodysplastic syndromes or Mds.

We're on track to provide follow up update from this AML Mds study by mid year and report initial data from the CH 49, Ibrutinib combination study by year end.

James E. Dentzer: We're on track to provide a follow-up update from this AML-MDS study by mid-year and report initial data from the CA-4948 Ibrutinib combination study by year-end. We also continue to be excited by the potential opportunities that could come out of the Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute that we announced in November, on the development of CA-4948, and from the IST being run by Dr. Platzbecker in Germany, studying CA-4948 as a treatment for anemia in patients with lower-risk MDS.

We also continue to be excited by the potential opportunities that could come out of the cooperative research and development agreement or crate up with the National Cancer Institute that we announced in November on.

On the development of CA 4948.

And from the I S T being run by Dr. <unk> Bekker in Germany, studying CA 4948, as a treatment for anemia in patients with lower risk Mds.

We will discuss them in greater detail later on this call.

James E. Dentzer: We will discuss them in greater detail later on this call, but both partnerships offer uniquely intriguing expansion potential, while also substantially increasing the number of patients we are able to reach in a population of dire medical needs and providing a de-risked opportunity to further develop CA-4948 in novel indications. Now, moving away from IRAP 4.

But both partnerships offer uniquely intriguing expansion potential.

While also substantially increasing the number of patients we are able to reach in a population of dire medical need.

And providing a day risk opportunity to further develop CA 4948 in novel indications.

Moving away from Iraq poor for a moment.

Also in 2020, we acquired rights received I, Andy Claris and initiated patient dosing.

James E. Dentzer: Also in 2020, we acquired rights, received IND clearance, and initiated patient dosing in a Phase 1A1B trial of CI-8993, our first-in-class monoclonal anti-VISTA antibody for the treatment of patients with relapsed or refractory solid tumors. We have continued to enroll patients and bring additional trial sites online for the study, and look forward to reporting initial safety and efficacy data in the second All told, in 2020.

In our phase one a one b trial.

Eight 993.

Our first in class monoclonal anti Vista antibody for the treatment of patients with relapsed or refractory solid tumors.

We have continued to enroll patients and bring additional trial sites online for the study.

And look forward to reporting initial safety and efficacy data in the second half of this year.

All told 2020.

In the fourth quarter in particular was a time of meaningful progress for the company, including the successful execution of key strategic financings.

James E. Dentzer: And the fourth quarter, in particular, was a time of meaningful progress for the company, including the successful execution of key strategic financing that has provided a robust foundation to support the continued advancement and expansion of our clinical programs in 2021 and the years to come. We look forward to building on this progress as 2021 shapes up to be another important year for Curis. With that... Let's dig into some detail on our ongoing clinical programs, starting with leukemia.

That has provided a robust foundation to support the continued advancement and expansion of our clinical programs in 2021 and the years to come.

We look forward to building on this progress as 2021 shapes up to be another important year for curious.

With that.

Let's dig into some detail on our ongoing clinical programs starting with leukemia.

We're evaluating CA 4948 in patients with relapsed or refractory AML or mds, including those with spliceosome mutations debt.

James E. Dentzer: We're evaluating CA4948 in patients with relapsed or refractory AML or MDS, including those with spliceosome mutations that drive the expression of the oncogenic long isoform of IRAC4. At ASH, we announced highly encouraging Phase I data from our ongoing monotherapy study, demonstrating marrow blast reductions observable in all evaluable patients, with two of six valuable patients experiencing a Since the last update, we have continued to gather data, and we have begun dosing patients at 500 milligrams BID after early indications at preceding doses were in line with what we had previously reported.

Drive the expression of the oncogenic long isoform of Iraq for.

At Ash, we announced highly encouraging phase one data from our ongoing monotherapy study demonstrating marrow blast reductions observable in all evaluable patients.

With two of six evaluable patients experiencing on Mero complete response.

Since the last update we have continued to gather data.

And we have begun dosing patients at 500 milligrams B I D. After early indications at preceding doses were in line with what we had previously reported.

We're looking forward to presenting updated data from this study by mid year.

James E. Dentzer: We are looking forward to presenting updated data from this study by mid-year, separate from this trial. We are especially pleased to partner with a renowned AML MDS clinician, Dr. Uwe Potsbecker, to initiate the Phase II LUCUS study, An Investigator-Sponsored Trial for the Treatment of Anemia in Patients with Lower Risk for MDS.

Separate from this trial.

We are especially pleased to partner with a renowned AML Mds clinician doctor moving parts Becker to initiate the phase II Lucas study on.

On investigator sponsored trial for the treatment of anemia in patients with lower risk Mds.

Following the promising preliminary data we presented in December in patients with relapsed refractory AML and high risk Mds, we were encouraged to explore whether CA 494 rate may also provide benefits in earlier stage Mds patients who are farther away from.

James E. Dentzer: Following the promising preliminary data we presented in December in patients with relapsed reflactory, AML, and high-risk MDS, we were encouraged to explore whether CA-4948 may also provide benefits in earlier stage MDS patients who are farther away from progression to AML. If this hypothesis bears out, it could lead to a potential breakthrough in the AML and MDS fields, as current erythropoiesis stimulating agents, or ESAs, that target anemia in genetically defined lower risk MDS can be effective, but this effect is often transient, culminating in progression to AML and further disease complications. With its direct, non-myelosuppressive targeting of IRAC4, and its already demonstrated robust durability profile

Progression to AML.

If this hypothesis bears out.

It could lead to a potential breakthrough in the AML and Mds field.

Current erythropoiesis stimulating agents or Esa is that target anemia in genetically defined lower risk Mds can be effective but this effect is often transient.

Culminating in progression to AML and further disease complications.

With its direct non Milo suppressive targeting of Iraq for.

And he's already demonstrated robust durability profile.

We believe CA 494 rate could potentially offer a safe and transformative disease modifying alternatives for patients in early stage or low risk Mds.

James E. Dentzer: We believe CA-4948 could potentially offer a safe and transformative disease-modifying alternative for patients in early-stage or low-risk MDF. Patient enrollment in this study is expected to begin in the second quarter of 2021, and it is anticipated to enroll up to 84 patients across two cohorts. Cohort A will be in Issa Refractory, or intolerant patients; cohort B in ESA naive patients; patients in both cohorts will receive 300mg of CA-4948 twice daily, VID, for 21 days in at least four repeating cycles lasting 28 days. The primary endpoint of the study is to evaluate the proportion of patients that develop an erythroid response, according to IWG 2018 criteria. Now, moving to lymphoma. As a refresher,

Patient enrollment in this study is expected to begin in the second quarter of 2021.

And is anticipated to enroll up to 84 patients.

Across two cohorts.

Cohort a.

We'll be in Esa refractory.

Or intolerant patients cohort b and.

On the Esa naive patients.

Patients in both cohorts.

We will receive 300 milligrams of CA 4948 twice daily B I D.

For 21 days in at least four repeating cycles lasting 28 days each.

The primary endpoint of the study is to evaluate the proportion of patients that develop an erythroid response, according to <unk> 2018 criteria.

Yeah.

Now moving to lymphoma.

As a refresher.

Our phase one dose escalation study of CA 4948.

James E. Dentzer: Our Phase I Dose Escalation Study of CA4948 for the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma includes patients with diffuse large B-cell lymphoma. Waldenstrom's macroglobulinemia, and oncogenic mid-88 mutation. We are currently in the expansion phase, evaluating patients being treated with 300 mg of CA4948 twice daily after observing clear dose response and tumor reductions at this level during the dose escalation phase of the study. In an oral presentation at ASH last December, we reported expanded clinical data from this study, highlighting durable reductions in tumor burden, that were observed in 6 of 7 evaluable patients treated with 300mg twice daily, single agent CA-4948, following a median of four prior lines of therapy, on the basis of these data, we determined 300 milligrams BID to be the optimal dose for further study as it appears to strike the most favorable balance of sustained anti-cancer activity, and Tolerability for Long-Term Treatment, which is critical for these extremely sick patients who have already progressed through several failed lines of treatment, to provide some additional context.

For the treatment of patients with relapsed or refractory non Hodgkin's lymphoma.

Includes patients with diffuse large b cell lymphoma.

Walton strong macro Colombian Amelia and oncogenic mid 88 mutations.

We are currently in the expansion phase.

Evaluating patients being treated with 300 milligrams of CA 4948 twice daily.

After observing clear dose response and tumor reductions at this level during the dose escalation phase of the study.

In an oral presentation at Ash last December.

We reported expanded clinical data from this study highlights.

Highlighting durable reductions in tumor burden.

Net were observed in six of seven Evaluable patients treated with 300 milligrams twice daily single agent CA 494 eight.

Following a median of four prior lines of therapy.

On the basis of these data.

We determined 300 milligrams PID to be the optimal dose for further study as it appears to strike the most favorable balance of sustained anticancer activity.

And Tolerability for long term treatment, which is critical for these extremely sick patients who have already progressed through several failed lines of treatment.

To provide some additional context. These data further supported a trend that first came into focus at ash 2019, where.

James E. Dentzer: These data further supported a trend that first came to focus at ASH 2019, where we presented a small but intriguing data set that suggested CA-4948 could establish IRAC-4 inhibition as a new mechanism of action, a novel way to treat patients with NHL as it delivered a compelling safety and efficacy profile, particularly at higher dose levels in a monotherapy setting. Throughout 2020, we had two primary goals for this study. First,

Where we presented a small but intriguing dataset.

That suggested CA four 948 could establish Iraq for inhibition as.

As a new mechanism of action on novel way to treat patients with NHL as it delivered a compelling safety and efficacy profile, particularly at higher dose levels in a monotherapy setting.

Throughout 2020, we had two primary goals for this study.

First.

We wanted to demonstrate proof of concept in a monotherapy setting.

James E. Dentzer: We wanted to demonstrate proof of concept in a monotherapy setting and establish IRAC4 inhibition as a new mechanism of action, a novel way to treat patients with NHL by delivering a compelling safety and efficacy profile, particularly at higher dose levels. This would provide an important read-through for our anticipated combination study; we sought to verify which of the efficacious dose levels offered the best balance of safety and efficacy, as shown in the data we presented and in our selection of 300 mg BID of CA4948 as the recommended phase 2 dose. We believe we clearly hit on both of those points.

Establishing Iraq for inhibition as a new mechanism of action on novel way to treat patients with NHL by delivering a compelling safety and efficacy profile, particularly at higher dose levels. This would provide an important read through.

For our anticipated combination study.

And second we.

We sought to verify which of the efficacious dose levels offered the best balance of safety and efficacy.

As shown in the data, we presented and in our selection of 300 milligrams B I D of CA 4948, as the recommended phase two dose we believe we clearly hit on both of those points.

It is important to highlight again.

James E. Dentzer: It is important to highlight again that these are extremely sick patients who have received a median of four prior lines of therapy before entering the study. That we have been able to observe any meaningful therapeutic effect in monotherapy and that those effects are durable over such an extended period of time is enormously encouraging and provides powerful affirmation of our plan to launch a combination study with a synergistic therapy like the BTK inhibitor ibrutinib. We initiated this combination study earlier this quarter.

That these are extremely sick patients who had received a median four prior lines of therapy before entering the study.

We have been able to observe any meaningful therapeutic effect in monotherapy and that those effects are durable over such an extended period of time is enormously encouraging.

And provided powerful affirmation of our plan to launch a combination study with a synergistic therapy like the <unk> inhibitor ibrutinib.

We initiated this covenant this combination study earlier this quarter.

Part of the Ash presentation also covered early data for two potential biomarkers that may support patient selection and enrichment efforts and we look forward to providing updated data on both biomarkers at ACR next month.

James E. Dentzer: Part of the ASH presentation also covered early data for two potential biomarkers that may support patient selection and enrichment efforts, and we look forward to providing updated data on both biomarkers at AACR next month. Now, let's talk a little bit about why we and key stakeholders in the NHL clinical community find the prospect of an IRAC4-BTK inhibitor combination so compelling. ETK inhibitors like ibrutinib are an approved, effective oral class of therapies for patients with various lymphatic cancers that work by targeting one of the main activators of NF-B and the BCR pathway. Crucially, however... Comprehensive NF-B regulation requires also shutting down mitosomal signaling in the TLR pathway, which is primarily controlled by IRAC-4, the target of CA-4948. In short, there are two pathways.

Now, let's talk a little bit about why we and key stakeholders in the NHL clinical community find the prospect of in Iraq for BT K inhibitor combination so compelling.

<unk> inhibitors like Ibrutinib arent approved effective oral class of therapies for patients with various lymphatic cancers.

That work by targeting one of the main activators of Nf Kappa B.

The BC our pathway.

Crucially however.

Comprehensive Nf Kappa B regulation requires also shutting down mid is almost signaling in the <unk> pathway, which is primarily controlled by Iraq for the target of <unk> hundred 94 eight.

In short two pathways.

The Bcl pathway and the <unk> pathway are primary and independent oncogenic drivers of Nf Kappa B.

James E. Dentzer: The BCR pathway and the TLR pathway are primary and independent oncogenic drivers of NF-B. Dysregulation of either of these two pathways drives excessive B-cell proliferation. BTK inhibition blocks 1, and IRAC4 inhibition blocks the other. We believe effective dual targeting of both pathways could provide substantially better outcomes than targeting either pathway alone. And while there are several companies with approved BTK inhibitors... There is only one company developing a BTK-IRAC4 combination. That company is called Curis.

Dysregulation of either of these two pathways drive success at B cell proliferation.

PTK inhibition blocks one.

Iraq for inhibition blocks the other.

We believe effective dual targeting of both pathways.

Could provide substantially better outcomes than targeting either pathway alone.

And while there are several companies with approved <unk> inhibitors.

There is only one company developing a BT K Iraq for combination.

That company is curious.

We are currently enrolling patients in the part one of the dose escalation component of the trial, which will enroll approximately 18 patients in a three plus three design with <unk> hundred 94, eight doses, starting at 200 milligrams PID and escalating to 300 milligram.

James E. Dentzer: We are currently enrolling patients in part one of the dose escalation component of the trial, which will enroll approximately 18 patients in a 3 plus 3 design, with CA4948 doses starting at 200mg BID and escalating to 300mg BID, and ibrutinib dose is appropriate for the patient's respective NHL subtype. The primary endpoints of the first part of the study are the maximum tolerated dose and Secondary endpoints are PK and preliminary FF.

B I D.

And a bruton at doses appropriate for the patients respective NHL subtypes.

The primary endpoints of the first part of the study our maximum tolerated dose and determination of the recommended phase two dose.

Secondary endpoints are PK and preliminary efficacy.

We will provide updates appropriately as we progressed through enrollment.

James E. Dentzer: We'll provide updates appropriately as we progress through enrollment and eventually move on to Part 2 of the study, but so far, from Scientific Hypothesis to preclinical data. [inaudible] Each step of the journey has been a consistent step forward in the long-term vision for CA-4948 in NHL, that IRAC-IV controls a critical pathway that is parallel and complementary to the BCR pathway, and that inhibiting IRAC-IV may provide increased benefit to the vast population of patients treated with a BTK inhibitor and help mitigate resistance to BTK therapy.

And eventually move on to part two of the study.

But so far.

From scientific hypothesis.

To preclinical data.

To clinical data.

Each step of the journey has been a consistent step forward in the long term vision for CA 494, eight in NHL.

Net Iraq for controls a critical pathway.

That is parallel and complementary to the Bcl pathway.

And that inhibiting Iraq for.

May provide increased benefit to the vast population of patients treated with a <unk> inhibitor and help mitigate resistance to <unk> therapy.

That is our vision for NHL.

James E. Dentzer: That is our vision for NHL, and we look forward to our next opportunity to update you on this program in the fourth quarter of this year. Now, I'd like to turn to CI 8993, our first-in-class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors, to provide a little background. We acquired rights to CI 8993 in Q1. We received IND clearance from the FDA in Q2, and we opened our first clinical site and dosed our first patient in Q3. Everything has moved incredibly quickly.

And we look forward to our next opportunity to update you on this program in the fourth quarter of this year.

Now I'd like to turn to Ci 8993.

Our first in class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors.

To provide a little back story.

We acquired rights to Ci 80, 993 in Q1, we.

We received IND clearance from the FDA in Q2.

And we opened our first clinical sites and dosed our first patient in Q3 everything has moved incredibly quickly.

Since then we've continued to open more clinical sites and enroll more patients.

James E. Dentzer: Since then, we've continued to open more clinical sites and enroll more patients. This is a target that we and the clinical community have long been excited about because of the critical role it plays in suppressing T cell activity when it is activated, and conversely, when VISTA is blocked or inactivated.

This is a target that we and the clinical community have long been excited about because of the critical role. It plays in suppressing T cell activity when it is activated.

Conversely, when Vista is blocked or inactivated.

It has been shown in preclinical studies to prevent T cell suppression.

James E. Dentzer: It has been shown in preclinical studies to prevent T cell suppression and thereby reactivate anti-tumor immune function. We also see significant combination potential, and in the future, may explore targeting VISTA in combination with certain synergistic therapies such as PD-1, PD-L1 or even CTLA-4 inhibitors. As preclinical studies suggest that blocking VISTA significantly improves the efficacy of those checkpoint regulators. Moreover, progress in the development of CAR T therapies and the broader immunotherapy space over the last decade has addressed previously limiting on-target side effects associated with VISTA pathway blockade, namely immune-mediated toxicity and cytokine release.

And thereby reactivate anti tumor immune function.

We also see significant combination potential.

And in the future may explore targeting Vista in combination with certain synergistic therapies, such as PD, one PDL, one or even <unk> four inhibitors as preclinical studies suggest that blocking vista significantly improves the efficacy of those checkpoint regulators.

Moreover, progress on the development of car T therapies, and the broader immunotherapy space over the last decade have addressed previously limiting on target side effects associated with Vista pathway blockade, namely immune mediated toxicity and cytokine release syndrome.

We believe <unk> 89 to 93 is the most advanced anti Vista antibody currently in clinical development.

James E. Dentzer: We believe CI-8993 is the most advanced anti-VISTA antibody currently in clinical development. The clinical community has already shown deep excitement and interest in this program, and we believe CI-8993 has the potential to be a game-changing cancer therapy. We look forward to reporting initial safety and efficacy data for this exciting program in the second half of 2020. To wrap up, I want to emphasize how proud I am of the entire team at Curis, who, in the midst of an ongoing global pandemic, have worked tirelessly to ensure we hit every ambitious goal we set for ourselves this year.

The clinical community has already shown a deep excitement and interest in this program and we believe Ci 89 to 93 has the potential to be a game changing cancer therapy.

We look forward to reporting initial safety and efficacy data for this exciting program in the second half of 2021.

To wrap up I want to emphasize how proud I am of the entire team at Trs.

So in the midst of an ongoing global pandemic.

Have worked tirelessly to ensure we hit every ambitious goal we set for ourselves this year.

It is a testament to their efforts that we find ourselves in a vastly different place than we were 12 months ago and that much closer to bringing our promising therapeutics to the patients they will serve the most.

James E. Dentzer: It is a testament to their efforts that we find ourselves in a vastly different place than we were 12 months ago and that much closer to bringing our promising therapeutics to the patients they will serve. I'm honored to work with them every day. With that, I'll turn the call over to Bill to review our financial results for the quarter.

I'm honored to work with them every day.

With that I'll turn the call over to Bill to review our financial results for the quarter.

<unk>.

Thank you Jim.

The year ended December 31, 2020.

Bill Steinkraus: For the year ended December 31, 2020, Curis reported a net loss of $29.9 million, or $0.61 per share on both a basic and diluted basis, as compared to a net loss of $32.1 million, or $0.97 per share on both a basic and diluted basis in 2019. For the fourth quarter of 2020, we reported a net loss of $7.5 million, or $0.11 per share, on both a basic and diluted basis, as compared to a net loss of $8.6 million, or 26 cents per share, on both a basic and diluted basis for the same period in 2019.

Our net loss of $29 9 million or 61 cents per share on both a basic and diluted basis as.

As compared to a net loss of $32 1 million or.

We're 97 per share on both a basic and diluted basis in 2019.

For the fourth quarter of 2020, we reported a net loss of $7 5 million or 11 cents per share on both a basic and diluted basis as compared to a net loss of $8 6 million.

Dollars or 26 per share on both a basic and diluted basis for the same period in 2019.

Revenues for the year were $10 8 million as compared to $10 million for 2019.

Bill Steinkraus: Revenues for the year were $10.8 million, as compared to $10 million for 2019. Revenues for both years comprised primarily of royalty revenues recorded on Genentech and Roche's Net Sales of Ariba. Revenues for the fourth quarter of 2020 and 2019 were $3 million and $3.3 million, respectively. Operating expenses for the year ended December 31, 2020 were $35.7 million, as compared to $34.4 million for the same period in 2019, and operating expenses for the fourth quarter of 2020 were $9.3 million as compared to $10.6 million. The same period in 2019.

Revenues for both years comprised primarily of royalty revenues recorded on Genentech.

And Roche has net sales of Airbus.

Revenues for the fourth quarter of 2020, and 2019 were $3 million from $3 $3 million respectively.

Operating expenses for the year ended December 31, 2020 with $35 $7 million.

As compared to $34 4 million for the same period from 2019 on.

Operating expenses for the fourth quarter of 2020.

Or $9 $3 million as compared to $10 6 million.

On the same period 2019.

Bill Steinkraus: Cost of royalty revenues, for $0.5 million for the years ended December 31, 2020, and 2019, and we're $0.2 million for both the fourth quarter of 2020 and 2019. Research and development expenses were $23.1 million for the year as compared to $22.3 million for 2019. R&D expenses were $5.6 million for the fourth quarter of 2020, as compared to $7.5 million for the same period in 2019. The decrease was primarily due to a decrease in clinical and manufacturing costs related to CA-170 and Femopenicillin.

Cost of royalty revenues from.

<unk> $5 million for the years ended December 31, 2020 and 2019.

And were <unk> $2 million for both the fourth quarter of 2020 and 2009.

Research and development expenses were $23 $1 million for the year as compared to $22 $3 million for 2019.

R&D expenses were $5 $6 million for the fourth quarter from 2020 as compared to seven $5 million from the same period in 2019.

The decrease was primarily primarily due to a decrease in clinical and manufacturing costs related to CA 170.

And Mr.

General and administrative expenses were $12 $1 million for the year ended December 31, 2020, as compared to $11 $6 million with same period 2019.

Bill Steinkraus: General and administrative expenses were $12.1 million for the year ended December 31, 2020, as compared to $11.6 million for the same period in 2019. General and administrative expenses were $3.5 million for the fourth quarter of 2020, as compared to $3 million for the same period in 2019. The increase was primarily due to an increase in personnel-related costs.

General and administrative expenses were $3 5 million for the fourth quarter of 2020 as compared to $3 million on the same period 2019.

The increase was primarily due to an increase in personnel related costs.

Net other expense was $5 million per the year ended December 31 2020 as.

Bill Steinkraus: Net other expense was $5 million for the year ended December 31, 2020, as compared to $7.8 million for the same period in 2019. For the fourth quarter of 2020 and 2019, net other expense was $1.2 million and $1.3 million, respectively. Net other expense primarily consisted of imputed interest expense related to future royalty payments. As of December 31, 2020, Curis' cash, cash equivalents, and investments totaled $183.1 million, which included net proceeds of $159.1 million from our follow-on public offering.

As compared to $7 $8 million from the same period 2019.

From the fourth quarter of 2020, and 2019 net other expense was $1 $2 million and $1 $3 million respectively.

Net other expense primarily consisted of imputed interest expense related to future royalty payments.

As of December 31, 2020, <unk> cash cash equivalents and investments totaled $183 $1 million, which.

<unk> net proceeds of $159 1 million from.

Our follow on public offering.

December 2020.

Bill Steinkraus: December 2020. As of December 31, 2020, there will be approximately 91.5 million shares of common stock outstanding. We expect that our existing cash, cash equivalents, and investments should enable us to maintain our planned operations into 2024. With that, I'd like to open the call for questions. Operator, we will now

As of December 31, 2020, there were approximately 91 5 million shares of common stock outstanding.

Yeah.

We expect that our existing cash cash equivalents and investments should enable us to maintain our 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 one on your Touchtone phone.

Operator: We will now begin the question and answer session. To ask a question, you may press star then 1 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 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Alethea Young with Cantor. Please go ahead.

If you are using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two at.

At this time, we will pause momentarily to assemble our roster.

Our first question comes from Alicia Young with Cantor. Please go ahead.

Hey, guys. Thanks for taking my questions and truly congrats on a very transformative last three or four months very cool to watch.

Alethea Young: Hey, guys. Thanks for taking my questions. And truly, congrats on a very transformative last three or four months. It's been very cool to watch. So yeah, a couple for me.

So yeah, a couple from me.

Alethea Young: You know, one, I just want to get, for this mid-year update, can you maybe frame for us or help us think about how many people maybe you might have, or kind of where you might be at on that timeline, and also just kind of frame enrollment. It sounds like it probably is going a little better than maybe I expected. My second question is about VISTA, the VISTA program.

One I just want to get for this midyear update can you maybe frame for us relative to think about how many people maybe you might have or you know kind of you know where you might be on that on that timeline and just and also just kind of frame enrollment it sounds like it probably has gone a little better than what maybe I expected. My second question is on Vista.

On the Vista program and do you think by the time you get to the end of the year that you'll be in place at a place where you could potentially assess efficacy or is it more going to be about whether this is eliciting like cytokine release syndrome.

Alethea Young: And do you think by the time you get to the end of the year you'll be in a place where you could potentially assess efficacy? Or is it more going to be about whether this is eliciting cytokine release syndrome, which I still think is a big milestone, but I guess I just wanted to know how you think about those two things and the possibility of some monotherapy. And then my third question is just if you can just go back and maybe talk to us a little bit about low-risk MDS, some of the IRAC-IV science, you framed it a little bit, but just go a little bit more into why you believe there's a connection and there's some degree of confidence in the IST that you're running. Thanks.

Which I still think it's a big milestone.

But I guess I just wanted to know how you think about those two things on the possibility of some monotherapy and then my third question is just if you can just go back and maybe talk to us a little bit about like with low risk M. D asked some of the the the Iraq for science, I think you've framed it a little bit but it just got a little bit more into you know why you believe there's a connection.

And there are some some degree of confidence in you know the I S T that you're running things.

Sure Hi Ali.

James E. Dentzer: Sure. Hi Alethea. Thanks for calling in. Of the three questions, I'm going to address the first two, and I'm going to ask Bob to chime in on the third.

Thanks for calling in.

So of the three questions I'm going to let me address the first two and I'm going to ask Bob to chime in on the third so the first on the mid year update.

James E. Dentzer: So, the first, on the mid-year update, I think our expectations for enrollment have been really great. You know, we were able to enroll six patients in the six months leading up to ASH, so it makes sense for a mid-year update that we would probably get, you know, another six patients on top of that. How many patients and how that enrollment moves forward to getting the data back and cleaned and invaluable patients identified prior to that update is going to remain to be seen, but somewhere in that range probably makes sense. For Vista.

I think our expectation enrollment has been really great.

We were able to enroll six patients in the six months, leading up to ash. So it makes sense for a mid year update that we would probably get another six patients on top of that how many patients.

And how that enrollment moves forward to getting the data back.

And cleaned.

<unk> patients identified prior to that update is going to remain to be seen but somewhere in that range probably makes sense.

In Vista.

James E. Dentzer: It's a little early for us to identify whether or not we're going to be able to identify or assess efficacy by year-end. And just to put this in context again, We originally believed going into this study that the window is probably going to be somewhere between 0.5 and 2.0 Mb per Kg, and we needed to escalate through the sub-therapeutic doses until we could get into that window. And where in that window we're gonna see efficacy is not really clear. Of course, the earlier we see it, at lower doses, the quicker we'll get to efficacy information, but it could well be at the back end of that window. We don't really know.

It's a little early for us to identify whether or not we're going to be able to identify assess.

Assess efficacy by year end and just to put this in context again.

We've originally.

Believed going into this study.

That the efficacious.

Window is probably going to be somewhere between 0.5, and two point Omega per kick.

And we needed to escalate through.

On the sub therapeutic doses until we can get into that window and we're in that window, we're going to see efficacy is not really clear of course the earlier, we see as the news at lower doses. The quicker, we will get to efficacy information, but it could well be at the back end of that window, we don't really know at this point.

James E. Dentzer: At this point, we're literally just enrolling our way through those sub-therapeutic doses. So hopefully, we'll be in a position by year end to talk about efficacy, but it's frankly a little too early for us to say at this point. It depends on how enrollment goes over the next three quarters. Bob, maybe you can talk a little bit about the low-risk MDS and the science behind that approach.

It's literally just enrolling our way through those sub therapeutic doses. So hopefully we will be in a position by year end.

To talk about efficacy, but it's frankly, a little too early for us to say at this point depends on enrollment goes over the next three quarters.

Bob maybe you can talk a little bit about the low risk Mds.

On the science to that approach.

Yes, exactly thank you Alicia Thats a really good question.

Robert E. Martell: Yeah, exactly. Thank you, Alicia. That's a really good question.

Low risk Mds is we think a perfect place to explore this drug and partly because this is where we see a lot of these spliceosome mutations first showing up the free.

Robert E. Martell: You know, low-risk MDS is, we think, a perfect place to explore this drug, partly because this is where we see a lot of these spliceosome mutations first showing up. The fact that the spliceosome mutations show up in early stages of MDS, such as low-risk MDS, suggests that, you know, the outcome, meaning the long IRAC4 isoform being created, this outcome is fundamental to the disease process and an early step in the evolution of MDS to AML, ultimately.

Fact that license from you taste and show up in early stages of Mds, such as low risk Mds suggests that the.

The outcome, meaning long Iraq for Isis.

License for them being created.

This outcome is fundamental to the disease process and an early step in the evolution of MBS too.

AML ultimately, so we think because of that and because of the high.

Robert E. Martell: So we think because of that and because of the high level of spliceosome mutations in that disease, this is gonna be really important. In addition to the spliceosome mutations that are known to create IRAC4 long, there are likely other causes of excess IRAC4 long. So we know even in early stage MDS, we have excess levels, and we guess approximately 50% of all patients with lower-risk MDS have excess IRAC4 long, even some patients who don't have specific spliceosome mutations. So there's a lot of biology that supports going into this early stage of disease.

High level on slides from mutations in that disease. This is going to be really important. In addition to the spliceosome mutations that are known to create Iraq for long there are likely other causes of excess Iraq for long. So we know even in early stage.

Mds we have.

Excess levels, and we get approximately 50% of all patients with lower risk Mds have excess Iraq for lawn, even some patients who don't have specific spliceosome mutations. So theres a lot of biology that supports going into this early stage of disease.

Alethea Young: Can I ask you just one follow-up? On the mid-year catalyst, should we think about that as ASCO, or would you be in a situation where you would just top-line it?

And Cathy just one follow up on the mid year catalyst is that so we think about the alco or where would you be on a situation where he would just topline it.

James E. Dentzer: So, I think it's going to depend, of course, on which conference we can get the abstracts submitted to and then, of course, which one accepts them for discussion. At this point, we're kind of leaping into it, but, you know, hopefully we'll be in a position to clarify that as we get closer to that date. Okay.

Just curious so I think it's going to depend of course.

This is Jim again Alicia.

I think it's going to depend of course on <unk>.

Each conference we can get the abstract submitted to and then of course, which one accepts the abstract for for discussion at this point, we're kind of leaving it open.

But hopefully we'll be in a position to clarify that as we get closer to that day.

Alethea Young: Okay, cool. I'll hop back in queue. Thank you very much. Excellent. Thank you.

Okay Cool I'll hop back in queue. Thank you very much excellent. Thank you.

The next question is from Ed White with H C. Wainwright. Please go ahead.

Operator: The next question is from Ed White with H.C. Wainwright. Please go ahead. Good evening, guys. Thanks for taking my questions.

Good evening guys. Thanks for taking my questions. So, perhaps just a couple of timing questions first.

Edward Patrick White: So, perhaps just a couple of timing questions.

With the Sis to Lucas study.

Edward Patrick White: With the Phase 2 Lucas study, I know enrollment doesn't begin until the second quarter of this year. I'm just wondering how you're thinking about timing for data.

Enrollment doesn't begin until the second quarter of this year.

Just wondering how youre thinking about timing to data.

Sure Hey, Ed how are you.

Okay.

Edward Patrick White: How are you?

Yes.

James E. Dentzer: So yeah, this study is an IST, so it's not gonna be as closely controllable by the company as a more typical study would be. So the advantage, of course, is twofold for us.

<unk> is an ISP, so it's not going to be as.

Closely controllable by the company as a more typical study would be so the the advantage of course is twofold for us first with any ISG. The cost is much lower but most importantly, <unk> is being run by the clinician that debt as the chairman of the European Mds Society.

James E. Dentzer: First, with any IST, the cost is much lower, but most importantly, this IST is being run by the clinician who is the chairman of the European MDS Society, so he's got all 17 of his sites on board to enroll this study. So while we can't typically control it, and we won't be seeing the data on an ongoing basis the way we would in a normal study, I would suggest we're very optimistic, and we were very pleased when Dr. Plotzbecker reached out to us and asked if he could run this study.

He's got all 17 of his sites.

On board to enroll this study so while we don't we can't typically controller, then we won't be seeing the data on an ongoing basis that we would the way we would in a normal study I would suggest we're very optimistic.

We were very pleased when Dr. <unk> reached out to us and asked if he could run. This study we think it's a perfect extension of the drug.

James E. Dentzer: We think it's a perfect extension of the drug based on the data we presented at ASH. We always planned, as you know, to do the combination study, and wherever we can get blast count reductions, that seems to be really exciting, but based on being able to get blast count reductions across the board and marrow responses, I think it was, as we've discussed earlier, we were really excited about the prospect of being able to pursue a monotherapy and go into earlier-stage disease as well.

Just on the data we presented at Ash.

We always had been planning as you know to do the combination study and wherever we can get blast count reductions that seems to be really exciting, but based on being able to get blast count reductions across the board and marrow responses.

I think it was as we've discussed earlier, we were really excited about the prospect of being able to pursue a monotherapy and go earlier stage disease as well so when Dr. <unk> brought his team on board and said he wanted to take this on.

James E. Dentzer: So when Dr. Plotzbecker brought his team on board and said he wanted to take this on, we were thrilled. So I hope it goes quickly, but we'll have to stay tuned, and we'll give you updates as we go.

We were thrilled so I hope it goes quickly.

But we'll have to stay tuned and we'll give you updates as we can.

Great Thanks, Jim and.

Edward Patrick White: Great, thanks, Jim. And another question, and sort of on timing, but how should we be thinking about the past two to registration? So.

Another question and sort of on timing, but how should we be thinking about the path too.

To.

<unk> so in NHL, we know that the priority is going to be in combination with ibrutinib.

Edward Patrick White: In NHL, we know that the priority is going to be in combination with Brutonib, but you have excellent data on monoclonal antibodies.

But you had excellent data in monotherapy after four lines of therapy, So just thinking about.

Edward Patrick White: [inaudible]

Edward Patrick White: What's the quickest path to approval?

What's the quickest path to approval, maybe you can walk through your strategy there.

James E. Dentzer: Maybe you can walk through your strategy there, you know, either combo or monotherapy. Sure, thanks, it's a great question.

You know either combo or our monotherapy.

James E. Dentzer: So the path to approval... is, of course, there are many different branches here. So first and foremost, let's think about AML and MDS differently from NHL. So, as you know, with AML and MDS, we may have one-path combination therapy, one-path monotherapy, and maybe some earlier stage. But to your question specifically addressing NHL, we think, you know, we are still pursuing monotherapy as an option. That trial is ongoing, and we, of course, are also very excited based on having patients that have been on so many prior lines of therapy that we are getting such clear indications of tumor shrinkage. Incredibly exciting.

Sure. Thanks.

A great question, so the path to approval.

Is is of course, there are many different branches here, so first and foremost, let's think about AML and Mds differently from any gel. So as you know with AML and Mds. We may have one path combination therapy, one path monotherapy and maybe some earlier stage, but to your question specifically addressing NHL.

We think we are still pursuing monotherapy is an option that trial is ongoing.

And we of course are also very excited based on on having patients that had been on so many prior lines of therapy that we were getting such clear indications of tumor shrinkage incredibly exciting. So we of course will be pursuing that as well.

James E. Dentzer: So we, of course, will be pursuing that as well. I think the long-term perspective, you know, we talk about this a lot when we go out and do presentations to investor communities. We think very differently about the commercial strategy versus the regulatory strategy. The commercial strategy, from my perspective, is incredibly clear.

I think the long term perspective.

We talk about this a lot when we go out and do presentations to Investor communities, We think very differently about the commercial strategy versus the regulatory strategy. The commercial strategy from my perspective is incredibly clear there are two pathways that drive Nf Kappa B.

James E. Dentzer: There are two pathways that drive NF-kappa-B, the BCR path and the TLR path. All the BTK inhibitors, including ibrutinib, block the BCR path, but we're the only ones that can block the TLR path.

The VCR path and the TL our path.

All the <unk> inhibitors, including Ibrutinib block the VCR path, we are the only ones that can block the DLR path.

The question really isn't it if you have one of these cancers, the question isn't which which pathway do you want to block or do you want a <unk> inhibitor or an <unk> inhibitor.

James E. Dentzer: The question really isn't, if you have one of these cancers, the question isn't which pathway do you want to block, or do you want a BTK inhibitor or an IRAC4 inhibitor? The real question, we suspect, in a commercial setting, is whether you want to be on both. So that's the primary driver behind going down this study, to evaluate it in the clinic and see if we can replicate the findings in the lab, which indicated that clearly this was the best treatment alternative.

Question, we suspect on a commercial setting as you want to be on both.

So that's the primary driver behind.

On a going down this study is less evaluated in the clinic and see if we can replicate the findings in the lab, which indicated that clearly this was the best treatment alternative.

Once we can establish that then we want to look at regulatory opportunity and Thats. When we have described the expansion stage of the combination therapy, we will be evaluating the force subtypes or for niche groups within NHL that we think might offer the fastest.

James E. Dentzer: Once we can establish that, then we want to look at regulatory opportunity, and that's when we've described the expansion stage of the combination therapy. We will be evaluating the four subtypes or four niche groups within NHL that we think might offer the fastest, highest probability of success path to getting a regulatory approval, to getting that first label. Long term, we want to get a label that allows physicians to prescribe this anywhere where they would prescribe a BTK inhibitor, anywhere where they would prescribe ibrutinib.

Probability of success path to getting our regulatory approvals to getting that first label.

Long term, we want to get a label that allows us to allows physicians to prescribe this anywhere where they would prescribe <unk> inhibitor anywhere where they would prescribe ibrutinib.

But for the first label, we're going to be studying and expansion in this current study.

James E. Dentzer: But for the first label, we're going to be studying an expansion of this current study, four groups. We're going to be looking for patients that are naive to BTK, with marginal zone lymphoma, primary CNS lymphoma, ABCDL-BCL, or patients who have been on ibrutinib and have developed adaptive resistance. Those are the four groups of patients that we think would offer the fastest path to registration. Which one of those paths is the best one or whether several of them look equally attractive is gonna remain to be seen when we get the data, but we're gonna be pursuing all of those and monotherapy simultaneously.

For groups, we're going to be looking for patients that are naive to be teekay with primary marginal zone I'm, sorry, with marginal zone lymphoma with primary CNS lymphoma with <unk>.

Or patients who have been on Ibrutinib and have developed adaptive resistance. Those are the four ones. The four groups of patients that we think would after offer the fastest path to registration, which one of those paths as the best one or whether you just several of them look equally attractive is going to remain to be seen when we get the data, but we're going to be pursuing.

All of those and the monotherapy simultaneously.

It was a pretty long answer, but it was a pretty pretty important question I hope that was helpful.

Operator: It was a pretty long answer, but it was a pretty important question. I hope that was helpful. No, that was very helpful. I appreciate the long explanation, So thanks a lot. Thanks for taking my question. The next question is from Soumit Roy with Jones Trading. Please go ahead.

No that was very helpful. I appreciate the long answer.

So thanks, a lot thanks for taking my questions.

The next question is from Tom at ROI with Jones trading. Please go ahead.

Hi, everyone. Thank you for taking the question.

Soumit Roy: Hi everyone, thank you for taking the question. First on the AML and DX front, it looks like ASH data was mostly 200 and 300 BIDNs. It has already started enrolling 500 PID cohorts. Is there a reason? Did you skip any? Or is there a reason for this fast enrollment with such a high dose cohort as I would think AML patients are more sensitive to these drugs? If you can add any color, and how many of these high-dose cohort patients should we expect in the mid-year update?

First on the email Index fund.

It looks like the Ash data was mostly 203 hundred B I D M.

It's already started.

Rolling price.

100 B.

Yeah.

Consider recent did you keep any hour the reason for this fast enrollment into such high.

Those cohort does I would think.

Patients are more sensitive towards these drugs.

You can add any color.

How many of these high dose cohort patient so should we expect the mid year update.

James E. Dentzer: First, thank you, Soumit, for calling in. I really appreciate your support and, obviously, as always, terrific questions about the AML and MDF study. I think that we announced, of course, that we're now dosing at 500. It's really a reflection of how fast the enrollment has gone.

Okay.

Thank you Sumit for calling in I really appreciate your support and obviously as always terrific questions in the AML and Mds study.

I think.

We announced of course that we're now dosing at 500, it's really a reflection of it has gone so fast.

Enrolment the excitement among the Kols is is as high as it is with us and with the with investors.

James E. Dentzer: The excitement among the KOLs is as high as it is with us and with investors. The data from this drug are really highly encouraging. So we've really been very successful at getting patients in, clearing doses, and getting on to the next efficacious dose. You may recall on the NHL side, we decided at the end that 300 milligrams was the right dose in AMO and MDF. These diseases are a little more aggressive than NHL.

On the data from this drug are a really highly encouraging so we've really been very successful at getting patients in clearing doses and getting onto the next efficacious dose you may recall on the NHL side.

We decided at the end of the 300 milligrams was the right dose.

In AML and Mds.

These diseases are a little more aggressive than NHL and in fact in an analysis of the safety profile of the patients that have been enrolled to date and the efficacy that we're seeing.

James E. Dentzer: And in fact, in an analysis of the safety profile of the patients that have been enrolled to date and the efficacy that we're seeing, the physicians were all very excited about pushing as high a dose as we could to try and find the best balance of safety and efficacy in this indication. And it would not surprise us, of course, that a higher dose would be more warranted in this population. To get the kind of impact that we've seen at 200 and 300 milligrams so far was really exciting, and of course, we want to see what that looks like as we go to higher levels. And how high it goes depends on how high we can go until we hit MTD.

On the physicians, we're all very excited about pushing as.

As higher dose as we can to try and find the best balance of safety and efficacy in this indication and it would not surprise us of course.

Debt, a higher dose would be more warranted in this population.

To get the kind of impact that we've seen at 200 300 milligrams. So far was really exciting and of course, we want to see what that looks like as we go to higher levels and how high it depends on how high we can go until we hit MTT.

Got it.

And on the earnings from the front.

Soumit Roy: And on the NHL front... What do you expect, like your expectation, what percent of these patients in the Ibrutinib combo trial would get Ibrutinib 9 versus Ibrutinib resistant relapse patients, if you have any clarity on that?

What do you expect like your expectation on what percentage of these patients in the brutal combo trial, what person patients. You think you would get book and I'm naive versus ibrutinib resistant or relapsed patients.

You have any clarity on debt.

Yes, actually I might defer to Bob on that question. So that's all right Bob.

James E. Dentzer: Yeah, actually, I might defer to Bob on that question, if that's alright. Bob?

Yes, well so all of the pace. So Jim went through three cohorts with Ibrutinib naive populations and so.

Robert E. Martell: Yeah, well, all of the patients Jim went through three cohorts with abrutinib-naive populations. And so we'll enroll patients into each of those groups and then a fourth cohort with patients who have had prior responses to abrutinib and then have subsequently progressed. In that case, they will just continue abrutinib, and we'll add on 4948. So about three out of the four groups will have an abrutinib-naive patient population.

We'll enroll patients into each of those groups and then a fourth cohort with pace.

Patients who have had prior.

Response to Ibrutinib and then subsequently progressed in that case. They will just continue a bruton had been will add on 40 948, so well about.

Three out of the four groups will have a group NIM naive patient population.

To answer your question, Yeah, Yeah, I didn't realize because it's a well defined cohorts got it yes.

Soumit Roy: Thank you and congrats on all the

Thank you and congrats on all the progress.

Operator: Thank you so much. I really appreciate it. Again, if you have a question, please press star then 1. The next question is from Yale Gen with Laidlaw & Co. Please go ahead.

Thank you so much really appreciate it.

Again, if you have a question. Please press Star then one.

The next question is from Yale Jen with Laidlaw <unk> Company. Please go ahead.

So I'll get off to do it and head Mike Congrats on the very rapid progress you guys have I.

Yale Gen: Good afternoon, and my congratulations on the very rapid progress you guys have made. I just have two quick questions. The first one is that I remember you guys talking about in other meetings that you're surprised that six out of six patients in the MDS trials all responded, but you don't know their reasons. And I assume that's something you will provide more details on, but just curious, just in case there are patients not having those mutations, what might be the theoretical thoughts of why the drug still works so well?

Just have two quick questions. The first one is that I remember you guys are talking about other meetings debt.

We were surprised that the stockpile of sick patients that are.

And Mds trials that all respond, but you don't know there.

Mutation status.

And I assume that's something you will provide more color on but just curious just in case there is patient on not.

Having those mutations what might be the theoretical thoughts on why that dropped steel work so well.

James E. Dentzer: Thank you, Yale, and thanks for calling in. Terrific question.

Thank you Joe and thanks for calling in terrific question I'm going to take a first part of that question, then I'm going to ask Bob to chime in as well on some of the scientific rationale.

James E. Dentzer: I'm going to take the first part of that question, and then I'm going to ask Bob to chime in as well on some of the scientific rationale. So first, you're exactly right. In the six out of six patients that we saw blast count reductions, that was a big surprise for us. We had expected, as you know, based on the mouse data, based on the literature, that we should only get blast count reductions in half the patient population. When we got blast count reductions in all six...

So far.

First you're exactly right in the six out of six patients that we saw blast count reductions that that was a big surprise for us.

We had expected as you know based on the mouse data based on the literature that we should only get blast count reductions in half the patient population.

When we got blast count reductions in all six day.

There are really only two conclusions possible. The first is that it's statistically possible, even though it's unlikely it's statistically possible, but all six of those patients had very elevated Iraq for long levels.

James E. Dentzer: There are really only two conclusions possible. The first is that it's statistically possible, even though it's unlikely, that all six of those patients had very elevated IRAC4Lung levels. What's more likely is that IRAC4-long is a much more sensitive driver of AML and MDS in humans than it was in my mice. So in mice, you looked like you had to have a 1.25% ratio, or a very high level of IRAC4-long, to be driving your cancer, and therefore for an inhibition to be helpful.

What's more likely.

Is that.

Debt Iraq for long is a much more sensitive driver of ammo on Mds in humans than it was in mice.

In mice.

Looked like you had to have a $1 two 5% ratio a very high level of Iraq for long to be driving your cancer, and therefore force inhibition to be helpful and in humans.

James E. Dentzer: And in humans, it looks like, based on the preliminary data, that it's more likely that the threshold is much lower for how much IREC4 long you need in order for it to be driving your cancer and in order for inhibiting that IREC4 to be helpful. So if we look forward to what are the key data points we're looking for in this mid-year update, one of them is, of course, for those six patients and for additional patients that have come on.

Looks like based on the preliminary data that it's more likely that the threshold is much lower for how much Iraq for long you need in order for it to be driving your cancer and in order for inhibiting that Iraq for to be helpful. So if we look forward to what are the key.

Data points, we're looking for in this midyear update.

One of them is of course for those six patients and for four additional patients that have come on.

We're now processing of course, the clinical samples and we've sent them out to a central lab, we're going to be collecting Iraq for el expression level data on those patients because we want to try and get a handle if that threshold isn't 50%. If we can address a broader group of the population on that well how low is that threshold or Conversely, how big is the percentage of that.

James E. Dentzer: We're now processing, of course, the clinical samples, and we've sent them out to a central lab. We're gonna be collecting IRAC4L expression level data on those patients because we wanna try and get a handle on it. If that threshold isn't 50%, if we can address a broader group of the population than that, well, how low is that threshold? Or, conversely, how big is the percentage of that population that might benefit from this drug? The second part of the question of what we're going to be looking for gets to sort of the mechanism of action.

Population that might benefit from this drug.

On the second part of the question of what we're going to be looking for gets to sort of the mechanism of action.

We had been anticipating all along that we might have an impact on blast counts and that's why this drug would be such a great add in combination therapy with any of the other therapies that might be available and in AML and Mds because it's a novel mechanism of action. It works differently and it's clearly efficacious as we can see in the blast count reductions.

James E. Dentzer: We had been anticipating all along that we might have an impact on blast counts, and that's why this drug would be such a great addition in combination therapy with any of the other therapies that might be available in AML and MDS, because it's a novel mechanism of action, it works differently, and it's clearly efficacious, as we can see in the blast count reduction. We think it's oral, it's a small molecule, it's not myelosuppressive, and it's clearly active as a single agent. This is a great combination therapy.

<unk>.

We think it's at all it's small molecule, it's not Milo suppressive.

Clearly active as a single agent. This is a great combination therapy.

James E. Dentzer: But because we're also getting responsive, As we said in the call earlier, we want to also evaluate if there's a potential here as a monotherapy and if there's a potential in earlier stage disease. We've addressed the earlier stage disease question with Dr. Plotzbecker's study. That will give us the answer there.

But because we're also getting responses.

As we said in the call earlier, we want to also evaluate if there is a potential here as a monotherapy and if theres a potential in earlier stage disease. We've addressed the earlier stage disease question with Dr. <unk> study, that's going to give us the answer there.

And in the in the other answer on whether monotherapy is appropriate. We're also going to be collecting the genomic profile of these patients so which of these patients have a spliceosome mutation.

James E. Dentzer: And in the other answer, whether monotherapy is appropriate, we're also going to be collecting the genomic profile of these patients. So which of these patients have a spliceosome mutation? We know that roughly 20% of the population has a specific spliceosome mutation. The remainder of the population that has elevated IRAC4 has it elevated for other reasons. It might be epigenetic reasons.

We know that roughly 20% of the population has a specific spliceosome mutation. The remainder of the population that has elevated Iraq or has it elevated for other reasons that might be epigenetic reasons, but 20% of the population. We would expect to have spliceosome mutation that means one out of the six patients that we dose probably.

James E. Dentzer: But 20% of the population we would expect to have a spliceosom mutation. That means one out of the six patients that we dose probably has a mutation. And then in the next group of six, we might see one or two patients as well. If we can get an outsized reaction and an outside response in those patients and potentially signs of heem recovery, we might have a monotherapy strategy available as well.

Has that mutation and then in the next group of six.

We might see one or two patients as well.

We can get an outsized reaction and those outside response in those patients and potentially signs of heme recovery, we might have a monotherapy strategy available as well so we're going to be looking at this midyear update.

James E. Dentzer: So we're going to be looking at this mid-year update, first. As we expand the higher number of N, do we continue to see this broad across-the-board blast count reduction of 50% of the population or more? Can we get a better handle on what that addressable population size might be?

Two.

First.

As we expand a higher number than do we continue to see this broad across the board blast count reduction in 50% of the population or more.

Can we get a better handle on what that.

Addressable population size might be.

James E. Dentzer: and then also... do we look at the protein expression levels and specifically the genetic mutation status of these patients to identify whether or not we might also have a monotherapy strategy? Bob, could you add a little more on the scientific rationale?

And then also.

Do we look at the at the protein expression levels and specifically the genetic mutation status of these patients to identify whether or not we might also have a monotherapy strategy.

Bob could you add a little more on the scientific rationale.

Yeah sure Hi, Thank you for the question. So I think Jim actually addressed a lot of the basic rationale on and I think one key aspect is that we don't know for sure yet.

Robert E. Martell: Yeah, sure. Hi Yael.

Robert E. Martell: Thank you for the question. So, I think Jim actually addressed a lot of the basic rationale, and I think one key aspect is that we don't know for sure yet what ratio of IREC-4 long to IREC-4 short will be appropriate in humans to predict potential efficacy. As Jim mentioned, all of the patients had some blast reduction with their initial doses of 4948. And so, we'll be reporting those ratios and the information at the mid-year update.

What ratio of Iraq for loan to Iraq for short will be appropriated.

Appropriate in humans to predict potential efficacy.

As Jim mentioned all of the patients had some blast reduction with their initial dosing with 4948.

And so.

We'll be reporting those ratios in the information that the mid year update.

And I think Thats, one big I think on another thing to consider also is that in Mds. It also in AML when components of the diseases, the inflammatory micro environment within the bone marrow.

Robert E. Martell: And I think that's one thing. But I think another thing to consider is that in MDS and also in AML, one component of the disease is the inflammatory microenvironment within the bone marrow. And that's obviously partially caused or largely caused by IRAC-4 driving that. And in fact, IRAC-4 is expressed to some level in all patients with AML and MDS. And so, to the extent that that's causing an inflammatory microenvironment, that can be mitigated by blocking IRAC-4, which is key in sort of mediating many of the inflammatory cytokines that come through this pathway. Does that address your question? Absolutely not.

And Thats, obviously, partially it caused are largely caused by Iraq for driving that and in fact, Iraq for long is expressed to some level in all patients with AML and Mds and so to the extent that that's causing an inflammatory microenvironment.

That can be mitigated by blocking Iraq for which is a key and sort of mediating.

Many of the inflammatory cytokines that come through this pathway.

Does that address your question.

Absolutely absolutely that's a very comprehensive very insightful weighted.

Yale Gen: Absolutely, that's a very comprehensive, very insightful answer. I appreciate that. Maybe it's just a quick one for Bill.

And so I appreciate that and maybe it's just a quick one for bill.

Yale Gen: 2021 will be a big year for a lot of activities. Do you have any sort of general guidance of thinking how much R&D will be more than increased compared to last year? And does the Lucas study cost companies any more money, or does it cost companies any more money? or basically will be supported fully by academic institutions in Europe.

2021 will be a big year for a lot of activity activities do you have any sort of general guidance of thinking how much R&D will be more than increased compared to last year and that's the Lucas study cost company.

He spent causes company any more money or basically will be supported fully by the academic institutions in Europe and thanks, Greg.

Bill Steinkraus: And thanks. Great. Yeah.

So I guess, maybe in reverse order.

Bill Steinkraus: Yeah, so I guess maybe in reverse order, the Lucas IST. We are providing financial support, but as Jim mentioned, it's at a much lower rate than a true sponsored study. So that's part of the investment that we've looked to make. Following the successful raise here in December, our main focus is making the investments into both these programs, 4948 and 8993, to ensure that we seize the opportunity here to deepen our development path as well as, you know, broadening opportunities like going to low-risk MDS.

So Lucas I see we are providing financial support but as Jim mentioned.

It's at a much lower rate than a sponsored study.

So that's part of the investment that we've looked to make following the.

Successful raised here in December.

Our main focus is.

Making the investments.

Both of these programs to one on freight and at 993 to ensure that we see the opportunity here.

And deepening our development path as well as broadening opportunities like going to low risk Mds. So.

Bill Steinkraus: So, it will take time to ramp up our cash burn, but I think, you know, I would expect for this year's cash burn to be about $12 million a quarter on average. There'll be some, like I said, it will take a little bit of time to scale up, but I think that's probably a more appropriate target than using the 2020 trend.

But it will take time to ramp up our our cash burn, but I think you know.

I would expect that as your cash burn to be about $12 million a quarter on average there'll be some like I said it will take a little bit of time to scale up, but that's probably more appropriate target them using the 2020 trend.

Yale Gen: Okay, great. Thanks a lot. Again, congrats.

Okay, great. Thanks, a lot and again congrats.

Yale Gen: Thank you, Yo. I really appreciate your support. 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 Denser, for any closing remarks. Thank you, Operator, 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 and Immunext 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.

Thank you really appreciate your support.

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 operator, 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 curious for their hard work and commitment.

And to our partners at origin and immune ex 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.

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Operator: ??