Q4 2023 Curis Inc Earnings Call

Operator: Go to Beadaholique.com for all of your beading supply needs! Beading supply needs!

Good morning, and welcome to curious as fourth quarter 'twenty twenty-three business update call.

Operator: Good morning, and welcome to Curis' fourth quarter 2023 business update 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 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.

Speaker Change: All participants will be in listen only mode.

Speaker Change: Should you need assistance. Please signal a conference specialist by pressing the Starkey followed by zero.

Speaker Change: 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.

Speaker Change: To withdraw your question. Please press Star then two.

Diantha Duvall: 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 Diantha Duvall, Curis' Chief Financial Officer. Diantha, please go ahead.

Please note this event is being recorded.

Speaker Change: I would now like to turn the conference over to Diantha Duvall curious as Chief Financial Officer Diantha. Please go ahead.

Diantha Duvall: Thank you and welcome to curious as fourth quarter 2023 business update call before we begin I would like to encourage everyone to go to our Investor section of our website at Www Dot curious dot com.

Diantha Duvall: Thank you and welcome to Curis's fourth quarter 2023 business update call. Before we begin, I would like to encourage everyone to go to our investor section of our website at www.curis.com to find our fourth quarter 2023 business update release and related financial table. 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 risks and uncertainties, and actual results may differ materially.

Diantha Duvall: Our fourth quarter 2023 business update release and related financial table.

Diantha Duvall: I would also like to remind everyone that during the call we will be making forward looking statements.

Diantha Duvall: What's your based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and actual results may differ materially.

Jim Dentzer: For additional details, please see our SEC filing. Joining me on today's call are Jim Dentzer, President and Chief Executive Officer, and Jonathan Zung, Chief Development Officer. We will also be available for a question and answer period at the end of our call. I'd now like to turn the call over to Jim.

Diantha Duvall: For additional details please see our SEC filings.

Diantha Duvall: Joining me on today's call are Jim Dentzer, President and Chief Executive Officer and Jonathan.

Jonathan: Chief Development Officer will also be available for a question and answer period at the end of our call.

Jonathan: I'd like to I'd now like to turn the call over to Jim Jim. Thank you.

Jim Dentzer: Thank you, Diantha. Good morning, everyone, and welcome to Curis' fourth quarter business update call. I'd like to start today's call with a look back over the past 12 months. Entering 2023, the whole biotech industry was struggling under the headwinds of a grim financial market. Curis faced all of that and the daunting challenge of seeing our leukemia study stalled on partial clinical hold with the FDA. In the face of that adversity, the Curis team rose to the challenge.

Jim Dentzer: Thank you Dan Good morning, everyone and welcome to curious this fourth quarter business update call.

Jim Dentzer: I'd like to start today's call with a look back over the past 12 months.

Jim Dentzer: Entering 2023, the whole biotech industry was struggling in the headwinds with a grin financial market.

Jim Dentzer: Curious faced all of that and the daunting challenge of seeing our leukemia study.

Jim Dentzer: Hold on partial clinical hold with the FDA.

Jim Dentzer: In the face of that adversity to curious team rose to the challenge we worked tirelessly in answering questions posed by the FDA. This included enrolling additional patients at 200 milligrams B I D and performing additional analyses.

Jim Dentzer: We worked tirelessly in answering questions posed by the FDA. This included enrolling additional patients at 200 milligrams BID and performing additional analyses. As a result, we were able to confirm the safety profile of Emma Concerted, gain alignment on the optimal dosing regimen for monotherapy, and secure the removal of the partial clinical hold a full quarter earlier than expected. We then redirected our energy to reopening clinical sites and enrolling new patients. In our monotherapy study, we are targeting a genetically defined population of relapsed refractory AML patients with a FLIP3 or spliceosome mutation. Enrollment is going quite well, and we expect to have a data update by mid-year. Well, that's pretty advanced.

Jim Dentzer: As a result, we were able to confirm the safety profile of them started.

Jim Dentzer: Gain alignment on the optimal dosing regimen for monotherapy and secure the removal of the partial clinical hold a full quarter earlier than expected.

Jim Dentzer: We then redirected our energy to reopening clinical sites and enrolling new patients in.

Jim Dentzer: Our monotherapy study, we are targeting a genetically defined population of relapsed refractory AML patients with a flip three or spliceosome mutations.

Jim Dentzer: Enrollment is going quite well and we expect to have a data update by midyear.

Well that study advances.

Jim Dentzer: We have initiated a frontline study of amylbuceratib in combination with azazitidine and venetoclax for all AML patients, regardless of their mutation status. This study is being conducted at sites in Spain, Germany, and Italy, and we expect preliminary data from this study in the second half of this year. All in all, a terrific year of progress in leukemia. Now, let's turn to our lymphoma program, which is generating an equally high level of excitement after reviewing initial data collected across multiple NHL subtypes. We focused our efforts on the ultra-orphan indication of primary CNS lymphoma, or PCNSL, where we are evaluating M of assertive in combination with Hebrew. We identified key sites and initiated enrollment. And in December, we released new clinical data for Relaxed Refractory PC-NSL at the ASH Conference in San Diego. The meetings we had with physicians at ASH were terrific.

Jim Dentzer: We have initiated a frontline study than what we started in combination with eases iodine and vanilla clocks for all AML patients regardless of their mutation status.

Jim Dentzer: This study is being conducted at sites in Spain, Germany, and Italy, and we expect preliminary data from this study in the second half of this year.

Jim Dentzer: All in all a terrific year of progress in leukemia.

Jim Dentzer: Now, let's turn to our lymphoma program, which is generating an equally high level of interest.

Jim Dentzer: After reviewing initial data collected across multiple NHL subtypes.

Jim Dentzer: We focused our efforts on the ultra orphan indication of primary CNS lymphoma or P. C N S L.

Jim Dentzer: Where we are evaluating <unk> in combination with Ibrutinib.

Jim Dentzer: We identified key sites initiated enrollment.

Jim Dentzer: And in December we released new clinical data in relapsed refractory P. C N itself.

Jim Dentzer: At the Ash conference in San Diego.

The meetings, we had with the positions at Ash were terrific and we were especially pleased to have Dr. Greg newer koski and Dr. Han torn from the Mayo clinic present the data.

Jim Dentzer: And we were especially pleased to have Dr. Greg Nowakowski and Dr. Han Tun from the Mayo Clinic present the data. As a reminder, frontline treatment in PCNSL is high-dose methotrexate and chemo, when that no longer works. There is no approved second line treatment.

Jim Dentzer: As a reminder.

Jim Dentzer: Frontline treatment and P. C N S. L is high dose methotrexate and chemo.

Jim Dentzer: That no longer works.

Jim Dentzer: There is no approved second line treatment.

Jim Dentzer: In our study three of five patients were able to achieve complete remission of their disease.

Jim Dentzer: In our study, three of five patients were able to achieve complete remission of their disease. It is admittedly a small number of patients. However, the response and interest from the clinical community have been very encouraging. In the eight weeks since ASH, our team has been fielding calls from clinical sites across the U.S. and Europe wanting to participate in our trials. In fact, by the end of Q1, we expect to have doubled the number of clinical sites versus where we were a year ago. Obviously, this is a reflection of the excitement about Emma Husserta, but it is also a reflection of the indefatigable effort of the Curis team. I couldn't be more proud.

Jim Dentzer: It is admittedly a small number of patients. However, the response and interest from the clinical community was very encouraging.

Jim Dentzer: In the eight weeks since ash, our team has been fielding calls from clinical sites across the U S and Europe wanting to participate in our trials.

Jim Dentzer: In fact by the end of Q1, we expect to have doubled the number of clinical sites versus where we were a year ago.

Jim Dentzer: Obviously this is a reflection of the excitement about the startup.

Jim Dentzer: But it is also a reflection of the indefatigable efforts I'd be curious team I couldnt be more proud.

Jim Dentzer: Finally in December.

Diantha Duvall: Finally, in December, we announced that we entered into an agreement for an investigator-initiated trial to study the combination of emirucertib and pembrolizumab in patients with metastatic melanoma. We're excited that this study presents an opportunity to expand upon the research done at academic centers and the NCI to explore the potential of Emma Hussert to Ben Solomon. In short, we had an incredibly productive 2023, and we look forward to continuing that momentum in 2024. With that, I'll turn the call back over to DeAntha to review our financial results for the quarter. DeAntha?

Jim Dentzer: We announced that we entered into an agreement for.

Jim Dentzer: For an investigator initiated trial.

Jim Dentzer: Study the combination of Amazon sorted and Timbral isn't that in patients with metastatic melanoma.

Jim Dentzer: We're excited that this study presents an opportunity to expand upon the research done at academic centers and the NCI to explore the potential of camera who starts are in solid tumors.

Jim Dentzer: In short we had an incredibly productive 2023.

Jim Dentzer: And we look forward to continuing that momentum in 2024.

Jim Dentzer: With that I'll turn the call back over to Dan to review, our financial results for the quarter Panther.

Diantha Duvall: Thank you, Jim. For the fourth quarter of 2023, Curis reported a net loss of $11.7 million, or $2.03 per share, as compared to a net loss of $11.3 million, or $2.35 per share, for the same period in 2022. Curis reported a net loss of $47.4 million, or $8.96 per share, for the 12 months ended December 31, 2023, as compared to a net loss of $56.7 million, or $12.14 per share, for the same period in 2022.

Dan: Thank you Jim.

Dan: For the fourth quarter of 2023 tariffs reported a net loss of $11 7 million or $2 three per share as compared to a net loss of $11 3 million or $2.35 per share for the same period in 2022.

Dan: Curious reported a net loss of $47 4 million or $8.96 per share for the 12 months ended December 31, 2023, as compared to a net loss of $56 7 million or $12.14 per share for the same period in 2022.

Dan: Revenues for the fourth quarter of 2023 were $2 7 million compared to $2 9 million for the same period in 2022.

Diantha Duvall: Revenues net for the fourth quarter of 2023 were $2.7 million compared to $2.9 million for the same period in 2022. Revenues net for the 12-month ended December 31st, 2023 were $10 million compared to $10.2 million in 2022. Research and development expenses were $10 million for the fourth quarter of 2023, compared to $8.7 million in 2022. The increase in R&D was driven by higher clinical development costs. R&D was $39.5 million for the 12 months ended December 31, 2023, compared to $43 million in 2022. General and administrative expenses were $4.9 million for the fourth quarter of 2023, compared to $4.3 million in 2022.

Dan: Revenues for the 12 months ended December 31, 2023 were $10 million compared to $10 2 million.

Dan: In 2022.

Dan: We should research and development expenses were 10 million for the fourth quarter of 2023 compared to $8 7 million in 2020 two.

Dan: The increase in R&D was driven by higher clinical development cost.

Dan: R&D was $39 5 million for the 12 months ended December 31, 2023, compared to 43 million in 2022.

Dan: General and administrative expenses were $4 9 million for the fourth quarter of 2023 compared to $4 3 million in 2022.

Dan: The increase in G&A was driven primarily by higher professional legal and consulting services.

Diantha Duvall: The increase in GNA was driven primarily by higher professional, legal, and consulting fees. GNA was $18.6 million for the 12 months ended December 31, 2023, compared to $19.6 million in 2022. Other income net was $0.5 million for the fourth quarter of 2023 compared to other expense net of $1.1 million in 2022. Other income net was $0.9 million for the 12 months ended December 31, 2023, compared to other expense net of $3.7 million in 2022. Other income expense net consists of interest income and non-cash expense related to the sale of future wealth.

Dan: G&A was $18 6 million for the 12 months ended December 31st 2023, compared to $19 6 million in 2022.

Dan: Other income net was <unk> 5 million for the fourth quarter of 2023 compared to other expense net of $1 1 million and 22.

Dan: Other income net was <unk> 9 million for the 12 months ended.

Dan: December 31, 2023 compared to other expense net of $3 7 million in 2022.

Dan: Other income expense net consists of interest income and noncash expense related to the sale of future royalties.

Dan: As of December 31, 'twenty twenty-three curious as cash cash equivalents and investments totaled $56 3 million and there were approximately $5 9 million shares of common stock outstanding.

Operator: As of December 31st, 2023, Curis' cash, cash equivalents, and investments totaled $56.3 million, and there were approximately 5.9 million shares of common stock out there. We continue to be in a solid cash position and expect that our existing cash, cash equivalents, and investments will enable our planned operations into 2025. 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 telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the key.

Dan: We continue to be in a solid cash position and expect that our existing cash cash equivalents and investments will enable our planned operations into 2025.

Speaker Change: With that I'd like to open the call for questions operator.

Speaker Change: We will now begin the question and answer session.

Speaker Change: To ask a question you May press Star then one on your telephone keypad.

Speaker Change: If you are using a speakerphone please pick up your handset before pressing the keys.

Operator: To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble the roster, and our first question will come from Ed White of H.C. Wainwright. Please go ahead. Good morning.

Speaker Change: To withdraw your question. Please press Star then two.

Speaker Change: At this time, we will pause momentarily to assemble the roster.

Speaker Change: And our first question will come from Ed White of H C. Wainwright. Please go ahead.

Ed White: Good morning, Thanks for taking my questions.

Jim Dentzer: Thanks for taking my question. Jim, you mentioned that in the primary CNS lymphoma trial, you have double the number of clinical sites open versus this time last year. I'm just wondering if you can let us know how many sites that are and how many sites you plan to open.

Ed White: Jim you mentioned that in the primary CNS lymphoma trial.

Ed White: You have a double of the clinical sites open versus this time last year I'm. Just wondering if you can let us know.

Ed White: How many sites that is and how many sites you plan to open.

Jim Dentzer: Yeah, we tried to get out of the details of the of the number of sites that we have at any given time because of course, we're always increase here, but I think the reason why we mentioned that this call is because it's a reflection of the kind of conference. We had obviously we are we were very encouraged by the by the data ourselves.

Jim Dentzer: Now, we try to get out of the details of the number of sites that we have at any given time because, of course, we're always increasing them, but I think the reason why we mentioned this call is because it's a reflection of the kind of conference we had. Obviously, we were very encouraged by the data ourselves. And if you were at us, you saw that our booth was incredibly busy, but that's been followed up by being able to get these new sites up and running and online.

Ed White: And if you were at Ash you saw that our booth was incredibly busy but that that's been followed up by being able to get these new sites up and running and online and we've got.

Jim Dentzer: And we've got, as I said, not the expectation that it will double by the end of Q1, but enthusiasm more broadly across the world, not just in the US. So it's really exciting from our perspective, and I'm hopeful that we can keep that momentum going forward. Hey, can you give us your thoughts on the size of that primary CMS lymphoma market? Sure, it's an ultra-orphan market.

Ed White: As I said not be expectation to to double by the end of Q1, but.

Ed White: Enthusiasm more broadly.

Ed White: Across the world not just in the U S. So it's really exciting from our perspective.

Ed White: And I'm hopeful that we can keep that momentum going forward.

Ed White: And can you.

Ed White: Give us your thoughts on the size of that primary CNS lymphoma market.

Speaker Change: Sure, it's an ultra orphan market. It's one of the reasons why we selected it. So if you think across the landscape of non Hodgkin's lymphoma.

Jim Dentzer: It's one of the reasons why we selected it. So if you think across the landscape of non-Hodgkin's lymphoma and everywhere where BTK gets used, of course, we have been targeting broadly. Anytime you use BTK, you're downregulating NF-kappa B from one pathway. There are a lot of BTK inhibitors targeting that path. We're the only one that targets the other path.

Speaker Change: And everywhere, where PTK gets used of course, we have been targeting broadly.

Ed White: Anytime you use PTK youre down regulating and a cap of B from one pathway.

Ed White: There are a lot of PTK inhibitors targeting that path, we're the only one that targets the other path.

Jim Dentzer: When we look across the landscape of non-Hodgkin's lymphoma, we focused in on primary CNS first because it's so small, incidence of five per million, that yields a lot of very attractive benefits from a development perspective, especially in conversations with regulatory authorities, but also within primary senile lymphoma. It's a fairly aggressive lymphoma where we believe we can address the disease quickly; as you saw in the data, the three of five complete responses; we got a glimpse of that in the first three months on treatment. So that's very helpful. And, of course, there are no effective treatments. There are no approved drugs for relapsed or refractory PCNSL.

Ed White: When we look across the landscape of of non Hodgkin's lymphoma.

Ed White: We focused in on primary CNS first because its so small incidence of five per million.

Ed White: That that yields a lot of very attractive benefits from a development perspective.

Ed White: Especially in conversations with regulatory authorities, but also within primary CNS lymphoma.

Ed White: It's a fairly aggressive lymphoma, where we can we believe we can address the disease quickly as you saw in the data.

Ed White: The three of five complete responses, we got a view of that than in the first three months of treatment.

Ed White: So that's very helpful and of course, there are no effective treatments. There are no approved drugs for relapsed refractory P. C. Myself. So we can go after a disease that is ultra orphan.

Jim Dentzer: So if we can go after a disease that is ultra-orphaned, where there are no approved treatments, and we can see this kind of response from the drugs, it's really encouraging. Hey, thanks, Jim.

Ed White: Where there are no approved treatments.

Ed White: And we can see this kind of response from the drug.

Speaker Change: It's really encouraging.

Speaker Change: Hey, Thanks, Jim and now from here, if I could just ask a big picture question.

Jim Dentzer: And now, perhaps, if I could just ask a big picture question, I wanted to get your thoughts on the potential for solid tumors. You had mentioned ISP beginning with, you know, in combination with Keytruda in metastatic melanoma. I just wanted to get your thoughts on that market in general, and solid tumors overall. Yeah, so solid tumors are really exciting. We had been, of course, from the very beginning in identifying this target.

Speaker Change: I wanted to get your thoughts on the potential in solid tumors. You had mentioned the I S. T beginning with the combination with Keytruda in metastatic melanoma.

Speaker Change: Wanted to get your thoughts on that market and large in solid tumors overall.

Speaker Change: Yeah, two solid tumors, there's really exciting we have been of course from the very beginning.

Speaker Change: And identifying this target one of the things that was so exciting was that the role of Iraq for oncology more broadly with something the curious had discovered and no one else knew about.

Jim Dentzer: One of the things that was so exciting was that the role of IRAC4 in oncology more broadly was something that Curis had discovered and no one else knew about. So when we were designing the molecule originally, we had the pharmacyclics template in mind of how you go after a blockbuster indication, you know, an indication with multi-billion dollar revenue potential when no one else knows about it yet, and we designed that molecule so that it would be effective in lymphoma but also would confer some competitive advantage in leukemia and in solid tumors. As you know, our first studies started in lymphoma, and that's, of course, where our most recent data are as well, and that's really compelling. The data in lymphoma, in the targeted populations that we would expect to hit, in the IRAC4 or spliceosome population and the FLT3 population, those data look really compelling.

Speaker Change: So when we were designing the molecule originally.

Speaker Change: We had the pharmacyclics template in mind, how do you go after a a blockbuster indication or an indication with multibillion dollar revenue potential when no one else knows about it yet.

Speaker Change: And we designed that molecule so that it would be affected in lymphoma, but also would would confer some competitive advantage in leukemia and solid tumors.

Speaker Change: As you know we are first studies started in lymphoma, and that's what of course, where our most recent data are as well and that's really compelling data in lymphoma in in the targeted populations that we would expect to hit in the Iraq for our spliceosome population and the flip three population those data look really compelling with.

Jim Dentzer: We've just started the frontline study, and then, to your point about melanoma, this is the first time we've gone into solid tumors. Now, there's been a lot of work done by the NCI and by academic centers in studying Emma Hussert have been various types of solid tumors. So, we know there's a lot of interesting work going on, for example, in bladder cancer, in gastroesophageal, in ovarian, in lung, in pancreatic. There are a number of different solid tumors where it looks like Hyret4 plays a significant role in where our drug might be able to confer benefit.

Speaker Change: Just start at the frontline study and then to your point in melanoma. This is the first time, we've gone into solid tumors now there's been a lot of work done by the NCI and by our by academic centers in studying them up we certainly been various types of solid tumors. So we know theres a lot of interesting work going on for example in bladder.

Speaker Change: Cancer.

Speaker Change: In gastroesophageal cancer.

Speaker Change: In ovarian and lung and pancreatic there are number of different solid tumors, where it looks like IraQ4 plays a significant role and where our drug might be able to confer benefit. This is the first time, we are going into that I think it's a little premature to talk about how large all of those markets are.

Jim Dentzer: This is the first time we're going into that, so I think it's a little premature to talk about how large all of those markets are. But the idea that we have a drug that looks as though it could provide an incremental benefit that no other drug does, in these very targeted markets individually and, of course, at a high level across the world of human solid tumors is really quite exciting. Thanks, Jim. And the last question: if I could,

Speaker Change: But the idea that we have a drug that looks as though it could provide incremental benefit that no. Other drug does in these very targeted markets individually and of course at a high level across the world of heme and solid tumors is is really quite exciting.

Speaker Change: Thanks, Jim and our last question for me if I could.

Speaker Change:

Speaker Change: Just wanted to get your thoughts on.

Jim Dentzer: Just wanted to get your thoughts on partnering, and product in solid tumors. Is that something that you'd be looking at, or is this something as you expand into solid tumors that you think you could fund on your own going down the Sure, so, I mean, take the melanoma study as a case in point. Obviously, that's a study we would rather not pay for. There are a lot of trials, maybe

Speaker Change: Partnering.

Speaker Change: The product in solid tumors is that something that you'd be looking at or is that something as you expand into solid tumors that you think you could fund on your own going down the road.

Jim Dentzer: Sure. So yeah, I mean take the melanoma study as a case in point, obviously, that's the study we would rather not pay for there.

Jim Dentzer: A lot of trials, maybe a thousand.

Jim Dentzer: There are a lot of clinical trials going on right now of a company's drug in combination with Pembro, Merck's PD-1, which most people consider deleting PD-1. But the way most of those work is they beg Merck to give them free drugs, and then they run the study. We have options. We're going to get data from this study, and we're the ones providing free drugs. Mark's the one picking up the tab for the study.

Jim Dentzer: There are a lot of clinical trials going on right now.

Speaker Change: Our company's drug in combination with Pembroke Merck's.

Speaker Change: Merck's PD, one which is most people consider it the leading PD one.

Speaker Change: But the way most of those work as they they begged Merck to give them free drugs.

Speaker Change: And then they run the study.

Speaker Change: We have the opposite.

Speaker Change: We're going to get data from this study.

Speaker Change: And we're the one providing free drug.

Speaker Change: It works the one picking up the tab for the study.

Speaker Change: Obviously, well you know what most companies would hope for is just getting free drug him.

Jim Dentzer: Obviously, what most companies would hope for is just getting a free drug. Ideally, if we're going to expand the number of clinical studies that we can run, whether it's in lymphoma or in leukemia or now in solid tumors, at the minimum, we'd like to get a 50-50 study. I think it's overly optimistic that we're going to be able to find all of our future studies 100% funded by the partner without giving up any rights.

Speaker Change: Ideally if we're going to expand the number of clinical studies that we can run whether it's in lymphoma Orient leukemia or now in solid tumors at the minimum we we'd like to get $50 50 study I think its overly optimistic that we're going to be able to find.

Speaker Change: All of our future studies are 100% funded by the partner without giving up any rights.

Jim Dentzer: But at this point in time, obviously, we're really excited that we're going to have the opportunity to get data across lymphoma, leukemia, and now solid tumors, and we can afford to do it. So, as long as we can afford to keep our rights and generate the data that show that this drug has such significant potential, I think that's our plan. Okay, great.

Speaker Change: But at this point in time.

Speaker Change: Obviously, where we're really excited that we're going to have the opportunity to get data across some soma leukemia, and now solid tumors and we can afford to do it.

Speaker Change: So as long as we can afford to keep our rights and generate the data that show that this drug has such significant potential I think that's our that's our plan.

Speaker Change: Yeah.

Speaker Change: Okay, great. Thanks for taking my questions you bet.

Jim Dentzer: Thanks for taking my question. You bet. The next question comes from Sumit Roy of Jones Trading. Please go ahead.

Speaker Change: The next question comes from Sumit Roy of Jones trading. Please go ahead.

Sumit Roy: Good morning, everyone and congratulations on all the progress on multiple fronts.

Jim Dentzer: Good morning, everyone, and congratulations on all the progress on multiple fronts. One question on the front line, the triple combo with Emma Bissett, Duneip, HMA, and Veneta Plax. You're starting, you mentioned three, three different countries in Europe.

Sumit Roy: One question on the frontline the triple combo with MLB sudden HMA and.

Sumit Roy: Vanilla slacks.

Sumit Roy: You mentioned three three different countries in the Europe are you planning on initiating some U S trial titanfall two.

Jim Dentzer: Are you planning on initiating some U.S. trial sites also? The second one... PCNS trials, is that in combination with Ibrutinib, or are you still planning to do monotherapy emibuzurtonate patients? Okay, so the first one first, so the initial study for the triplet, we're really targeting some sites where we think we can get data relatively quickly because we want to, in these early stages, the most important thing is to generate the data as quickly as we can and prove that the triplet works. We've got a lot of preclinical data that suggests that IRAC-IV is the primary driver of disease in half of all ANL patients. There's a published article, as you know, the Smith-Chaudhry article that was published in Nature in 2019 pointed that out.

Speaker Change: The second thing as I said.

Speaker Change: Go ahead, Keith Phoenix trial.

Sumit Roy: Is that in combination of an improved enable are still if you are planning to do monotherapy came up with Internet page.

Sumit Roy: Patients.

Sumit Roy: Okay. So the first one first.

Sumit Roy: So the initial study for the triplet.

Sumit Roy: We're really targeting some sites, where we think we can we can get data relatively quickly.

Sumit Roy: Because we want it in the early stages. The most important thing is to generate the data.

Sumit Roy: As quickly as we can improve the triplet works, we've got a lot of preclinical data that suggests.

Sumit Roy: That Iraq for.

Sumit Roy: Is the primary driver of disease and have a ball AML patients. There's a published article as you know the Smiths Chaudhry article that was published in nature in 2019 pointed that out half of all patients. This is the number one driver of disease in the other half of patients. It's not the number one driver of disease, but it is a secondary or tertiary.

Jim Dentzer: In half of all patients, this is the number one driver of disease. In the other half of patients, it's not the number one driver of disease, but it's a secondary or tertiary driver. So really, this should provide incremental benefit from a new mechanism that no other drug does. So the long-term strategy to capture as many patients as we can is, of course, to go frontline in combination with standard of care. That's Aces, Iodine, and Venetoclax.

Sumit Roy: Right.

Sumit Roy: So really this this should provide incremental.

Sumit Roy: Incremental benefit from a new mechanism that no other drug to us.

Sumit Roy: So the long term to capture as many patients as we can is of course go frontline in combination with standard of care, that's eases iodine and fanatical acts.

Jim Dentzer: So our hope would be that we can recapitulate in humans what we found in the lab. And that is, when do you add hemoglucerative to ASA or to Venn or the A-to-Venn combo.

Speaker Change: So our hope would be that.

Speaker Change: If we can recapitulate in humans.

Speaker Change: We found in Moab.

Speaker Change: And that is whether you add who started to Asia.

Sumit Roy: Board event or the <unk> combo.

Jim Dentzer: This significantly increases the efficacy of that standard of care treatment. So that's what we found in the lab. And again, that's what we want to try and identify very quickly, um, if possible, in the clinic. And, of course, we always want to check for safety.

Sumit Roy: This significantly increases the efficacy of that standard of care treatment. So that's what we found in the lab, but again, that's what we want to try and identify very quickly.

Sumit Roy: If possible in the clinic and of course.

Sumit Roy: We always want to check for safety.

Jim Dentzer: ASA and VEN, as you know, are a pretty tough regimen to tolerate. They're effective, but they're pretty tough to tolerate. Anecdotally, half of all patients that go on that ASA and VEN doublet have to discontinue treatment. So what we're going to be doing in the early days is putting patients on and confirming that there is no safety overlap, as we have. And then second, of course, we're going to be looking for that efficacy signal. And if you want to do that kind of exploration quickly, it really helps to identify the sites that you can focus on in a very concentrated way.

Sumit Roy: And then as you know are are pretty tough regimen to tolerate they're effective but they're pretty tough to tolerate anecdotally have a ball patients that go on that as a bad doublet have to discontinue treatment. So what we're gonna be doing in the early days, it's putting patients on it confirming that there is no safety overlap as we expect and then second of course, we're gonna be looking for that.

Sumit Roy: That efficacy signal and if you want to do that kind of exploration quickly.

Sumit Roy: It really helps to identify the sites that.

Sumit Roy: That you can focus on in a very concentrated way and those are the sites we've chosen to initiate that study.

Jim Dentzer: And those are the sites we've chosen to initiate that study, and your second question, could you remind me? Yeah, that's what I understand. So on the PCNSL trial, are you expecting to get front-line patients? To get to that, do you want to combine this with a Brexit or a Brutonate?

Sumit Roy:

Sumit Roy: Your second question could you remind me yeah, that's totally understand so on the PC NSM Ah trial.

Sumit Roy: Are you expecting to get frontline patients.

Speaker Change: So not to get to that do you want to combine that with effective coordinated yeah. That's the plan.

Jim Dentzer: Yeah. What's the plan? No, thank you.

Speaker Change: No. Thank you. Thank you for that so right now the combination is amongst searches and ibrutinib and it's in relapsed refractory patients.

Jim Dentzer: Thank you for that. So right now, the combination is amoxirtib and endibrutinib, and it's in relapsed refractory. And that's the initial starting point. And again, the rationale for the first combination of EMA and ibrutinib is clear: in the case of lymphoma, the problem driving disease for patients with NHL is NF-kappa-B overactive. So when NF-kappa B is overactive, what happens is it disrupts the apoptotic process of the malignant cell.

Sumit Roy: And that's the initial starting point and again the rationale for first the combination of <unk> and Ibrutinib that one is clear.

Sumit Roy: In the case of lymphoma.

Sumit Roy: But the problem driving disease for patients with NHL.

Sumit Roy: <unk> Nf Kappa B over activity.

Sumit Roy: So when when Nf Kappa B is is overactive what happens is it is it disrupts.

Sumit Roy: The apoptotic process of the malignant cells.

Jim Dentzer: So if you're on a BTK inhibitor today, the reason you're on that BTK inhibitor is that it blocks the BCR pathway, which is one of two pathways driving NF-kappa B over X. We now know that that's effective. You get a pretty high response rate with BTK inhibitors. And, in fact, as you know, it's a 10 to $15 billion market today.

Sumit Roy: So if you're on a PTK inhibitor today. The reason you're on that PTK inhibitor is that it blocks. The VCR pathway, which is one of two pathways driving Nf Kappa b over activity.

Sumit Roy: We now know that that's affected you get a pretty high response rate on PTK inhibitors and in fact as you know its a $10 billion to $15 billion market. Today Ibrutinib itself is 10 billion of that the abbvie.

Jim Dentzer: Ibrutinib itself is 10 billion of that, the J&J drug. What we're looking to do in lymphoma is hit NF-kappa B as hard as we can. There are now five big pharma companies that are chasing after BTK inhibitors of various flavors, covalent or non-covalent, all of them working effectively the same way, all of them blocking that BCR pathway, driving NF-kappa B. However, the second pathway, the toll-like receptor pathway, is currently unaddressed.

Sumit Roy: J&J drug.

Sumit Roy: What we're looking to do in Soma.

Sumit Roy: He has hit Nf Kappa B as hard as we can.

Sumit Roy: There are now five big pharma companies that are chasing after PTK inhibitors of various flavors covalent or non covalent all of them working effectively the same way all of them blocking that D C. Our pathway.

Sumit Roy: Nf Kappa B.

Sumit Roy: The second pathway the toll like receptor pathway is currently unaddressed.

Jim Dentzer: Curis is the only company that has a drug that blocks that path. That's another certainty. It binds to mid-88 imidazole.

Sumit Roy: <unk> is the only company that has a drug that blocks that Pat that's come up who started.

Sumit Roy: I estimate 88 zone and with out that binding and the absence of Iraq War zone, and the toll like receptor pass more broadly shut down.

Jim Dentzer: And without that binding, in the absence of Iraq's war, the imidazole and the Tolec receptor pathway would have more broadly shut down. So it stands to reason, when you step back, if you have lymphoma that's effectively treated by VTK, you'll always want to block NF-kappa B or down-regulate NF-kappa B as strongly as you can.

Sumit Roy: So it stands to reason when you step back.

Sumit Roy: If you have lymphoma, that's effectively treated by B T K.

Sumit Roy: You always want to block.

Sumit Roy: The Nf Kappa b or down regulated and it's got to be as strongly as you can so.

Jim Dentzer: So hit the BCR path with BTK, hit the toe-like receptor path with direct force, the combination, not monotherapy, the combination should always be better than either one alone. And that's what we found in the lab. And of course, that's what we're finding so far in the clinic. So that's the logic for the combination with dental resurgence. In terms of going to frontline, eventually, of course, you know, we would like to suggest that the long-term possibility that we're going to explore is, is this an opportunity to have a companion? Frontline Standard of Care with BTK across non-Hodgkin's lymphoma.

Sumit Roy: Hit the VCR path would be T K.

Sumit Roy: Hit the toll like receptor path with Iraq War.

Sumit Roy: The combination not monotherapy combination should always be better than either one alone and that's what we found in the lab and of course, that's what we're finding so far in the clinic. So that's the logic for the combination with them will be started in terms of going to frontline.

Speaker Change: Of course, you know it.

Speaker Change: We would like to suggest that the long term possibility that we're going to explore is is this an opportunity to have a companion front.

Speaker Change: Frontline standard of care with B T K.

Speaker Change: Across non Hodgkin's lymphoma, that's a little premature for that we've chosen primary CNS lymphoma, as our proof of concept indications to prove it out and we've been able to show that we can generate data pretty quickly, but long term I think of course, we're going to want to frontline in combination with PTK inhibitors.

Jim Dentzer: That's a little premature for that, but we've chosen primary CNS lymphoma as our proof-of-concept indication to prove it out, and we've been able to show that we can generate data pretty quickly. But long-term, I think, of course, we're going to want to go frontline in combination with BTK inhibitors. For now, having an ultra-orphan indication where we can go into the relapsed refractory setting where there are no drugs approved, that should offer a pretty compelling regulatory opportunity. So that's why we're going down that. I have a pretty long answer. I hope it was helpful. No, you have got it.

Speaker Change: For now having an ultra orphan indication, where we can go into the relapsed refractory setting where there are no drugs approved that should offer a pretty compelling regulatory opportunity. So that's why we're going down that path.

Speaker Change: Great I'm pretty long answer I hope it was helpful.

Speaker Change: Got it and speaking of companion.

Jim Dentzer: And speaking of companion, since you're moving into the solid tumor space, I'm curious if you're gonna push forward the companion diagnostic for the IRAC-4 mutation assay, and if that would be helpful in kind of carving out the market, both for inside the solid tumor space and also eventually in the leukemia setting. Yeah. So the short answer is yes. The long answer is it's a little more complicated.

Speaker Change: Since you are moving into the solid tumor and I'm curious if you're going to push forward the companion diagnostic for Iraq for.

Speaker Change: Mutation.

Speaker Change: S a and if that would be helpful.

Speaker Change: In a kind of a car in the market both for inside the solid tumor space and also eventually in the leukemia.

Sumit Roy: Yeah.

Speaker Change: So the short answer is yes. The long answer is it's a little more complicated so that in the short answer.

Jim Dentzer: So in the short answer, are we pursuing... the identification and regulatory path for a companion diagnostic for IRAC-4 expression? The answer is yes, absolutely. The more complicated answer is, we don't want that to slow down our path to developing and making this drug available for patients. So the way we're ensuring that FAST is passed is in monotherapy on the leukemia side, where we're looking to go into patients that have either a Flip 3 mutation or an IRAC4 overexpression. We're gonna target the IRAC4 population using spliceosome mutations. Now, spliceosome mutations are a subset of patients that overexpress direct war. The reason why you'd go after spliceosome mutations is that those mutations are already identified in existing gene panels.

Sumit Roy: We are pursuing.

Sumit Roy: The identification in the and the regulatory path for a companion diagnostic for Iraq swore expression and the answer is yes, absolutely.

Sumit Roy: In the more the more complicated answer is we don't want that to slow down.

Sumit Roy: Our path to development and making this drug available for patients.

Sumit Roy: So the way, we're we're ensuring that fastest path.

Sumit Roy: He is in monotherapy in leukemia side, where we're looking to go into patients that have either a plus three mutation or in Iraq War.

Sumit Roy: Over expression, we're going to focus the Iraq for population using spliceosome mutations have spliceosome mutations or a subset.

Sumit Roy: Of patients that over express Iraq War.

Sumit Roy: The reason why you'd go after spliceosome mutations as those mutations are already identified an existing gene panels.

Jim Dentzer: So a companion diagnostic is much easier. We don't need to have a new assay identifying NREC4. We can just lean into the existing panels, the Illumina panel, the Foundation One panel, places like MD Anderson that have a proprietary gene panel. These panels are already run on their existing patients, and we can lean into that and say, if you have one of these specific mutations, by definition, you have IREC-IV expression, and use that as our mechanism. But longer term, of course, we're going to want to diagnose and separate. Thank you again. It's the logic for going frontline in combination.

Sumit Roy: So a companion diagnostic.

Sumit Roy: Is it is much easier we don't need to have a new assay identified Eric before we can just lean into the existing panels. The alumina panel. The foundation one panel places like MD Anderson that have a proprietary gene panel. These panels are already run on their existing patients and we can lean into that and say if you have one of these specific mutations by definition.

Sumit Roy: You have Iraq for expression.

Sumit Roy: Could you use that as our mechanism, but longer term of course, we are going to want a diagnostic.

Speaker Change: Thank you again.

Speaker Change: The logic going frontline in combination what we're gonna go all comers, where we won't need a companion diagnostic.

Jim Dentzer: We're going to go all-comers, where we won't need a companion diagnosis. Thank you again for taking all the questions and congratulations. Sure. Thank you. The next question comes from Lee Watsik of Cancer Fitzgerald. Please go ahead. Hey, good morning.

Speaker Change: Thank you again for taking all the questions and congrats on your phone.

Speaker Change: Sure. Thank you.

Speaker Change: The next question comes from Lee <unk> of Cantor Fitzgerald. Please go ahead.

Lee: Hi, good morning, Thanks for taking our questions Jim I guess for the data that you are.

Jim Dentzer: Thanks for taking our questions. Jim, I guess for the data that you're going to present from the leukemia study around mid-year, maybe just, you know, set the expectations for us a little bit, what the data set that we are going to see, what the bar is for SIRI as well as for spliceosome mutations. And then for the combo data that's going to come out in the second half of this year, maybe tell us a little bit about the bar here, because, you know, AZVN, as we know, the bar is fairly high, it's pretty effective. And also, as you alluded to earlier about, you know, toxicities, and do you expect any overlapping toxicity with this regimen? Yeah, thank you, Lee.

Lee: Going to present in the leukemia study around midyear, maybe Jeff you know set expectations for us a little bad one data set that we.

Lee: Are going to see what the bar is for four three as well as for spices all mutations.

Lee: And then for the combo would tell you that that's gonna come second half of this year, maybe California little bad about the partner because you know he's a man as we know.

Lee: The barring family highs pretty effective and also as he alluded to earlier about you know toxicity 70 weeks bagged and overlapping tox with this regimen.

Speaker Change: Yeah. Thank you Lee.

Jim Dentzer: Appreciate you dialing in. So on those questions, first, in terms of the number of patients, we've consistently said what we'd like to have is a data set of 10 to 20 patients where, you know, we now have a data set of three patients in spliceosome, three patients in FLT3 at our target dose, and five patients, of course, in primary CMS. We'd like to increase that data set to N equals 20 to 50, somewhere in that range.

Speaker Change: You dialing it so on those questions.

Speaker Change: First in terms of the number of patients.

Speaker Change: We've consistently said what we'd like to have.

Speaker Change: Is the data set of 10 to 20 patients where we now have a dataset of three patients.

Speaker Change: In spliceosome, three patients and flit three at our target dose and five patients of course in primary CNS, we'd like to increase that dataset to an N equals 20 to 50 somewhere in that range.

Speaker Change: I hope that we're going to be in a position where we've got data collected of course, you can enroll the patients treat them follow them for a period of time and then assess the responses. My hope is that would be in a position to have that level of and that level of data in leukemia, spices home and slipped three by mid year and inland.

Jim Dentzer: I hope that we're going to be in a position where we've got data collected. Of course, you enroll the patients, treat them, follow them for a period of time, and then assess the responses. My hope is that we'll be in a position to have that level of N, that level of data, in leukemia, spliceosome, and SLEP3 by mid-year, and in lymphoma by year-end. In terms of the benchmark, what we think we need to do to be effective in the monotherapy side, we're targeting a CRCRH of 20%, the lower bound in the low teens, Of course, our first three patients look better than that, but let's not get ahead of ourselves.

Speaker Change: By year end in terms of the benchmark.

Speaker Change: What we think we need to do to be effective in the monotherapy side is we're targeting a CR CRH of 20%.

Speaker Change: Lower bound in the in the low teens 12, 13% kind of lower bounds.

Speaker Change: But at a 20% CR CRH rate.

Speaker Change: In.

Speaker Change: Salvage line therapy.

Speaker Change: For either flit, three or slices home in leukemia. We think is very compelling of course, our first three patients look better than that but let's not get ahead of ourselves. It's only three patients as we get to 10 to 20 patients what we'd really hope is that we can clear that CR rate SCR CRH rate of 20%.

Jim Dentzer: We've only got three patients. As we get to 10 to 20 patients, what we'd really hope is that we can clear that CR-CRH rate of 20% and be compelling on the lymphoma side, because there are no existing treatments. And that bar is probably lower. What we do know is that the largest data set available for BTK as a monotherapy in primary CNS lymphoma was a study of 52 patients. The CR rate was 19%.

Speaker Change: And because all of them.

Speaker Change: On the lymphoma side.

Speaker Change: Because there are no existing treatments.

Speaker Change: That bar is probably lower.

Speaker Change: What we do know.

Speaker Change: Is that the largest data set available for teekay as a monotherapy in primary CNS lymphoma was a study of 52 patients with CR rate was 19.

Speaker Change: So you would expect.

Jim Dentzer: So you'd expect, you know, one out of five patients would have, again, roughly a 20% CR rate in that population, and that's in DTK-naive patients. Once they've failed BTK, you would expect that rechallenging them with BTK yet again probably wouldn't work at all. You might expect zero out of five. That we're getting three out of five so far is obviously highly encouraging. I don't think we need to maintain quite that break.

Speaker Change: One out of five patients are again, roughly at 20% CR rate in.

Speaker Change: In that population and that's in BT T naive patients.

Speaker Change: Once they failed B T K you'd expect that re challenging them with B T. K, yet again, probably wouldn't work at all you might expect zero to five.

Speaker Change: We're getting three of the five so far.

Speaker Change: Is obviously highly encouraging.

Speaker Change: I don't think we need to maintain quite that rate.

Jim Dentzer: But if we can maintain in DTK-experienced patients a 20% or higher CR rate in lymphoma, I think that we've got a very compelling data set to have a discussion about that. So 10 to 15, I'm sorry, 10 to 20 patients in all indications is what we're hoping for. We look to be in a position to have data in that range for leukemia by mid-year and for lymphoma by year-round, and Overlapping Toxicities with AIDS. Oh, yes. Yeah. Yeah, so that's the number one thing to look for in the triplet.

Speaker Change: If we can maintain and beauty K experienced patients of 20% or higher CR rate in lymphoma.

Speaker Change: I think that we've got a very compelling data set to have a discussion with FDA. So 10 to 15, I'm sorry, 10 to 20 patients in all indications is what we're hoping for we look to be in a position to have data in that range.

Speaker Change: Leukemia by mid year.

Speaker Change: And for lymphoma by year end.

Speaker Change: And overlapping toxicities with <unk>, Oh, yes, yeah, yeah. So that's the number one thing to look for in the triplet.

Jim Dentzer: Of course, it makes sense that if you looked at our preclinical data, and we've got a really nice outline of the preclinical data in our corporate docs, it's very clear that from an efficacy perspective, in the lab, we were able to add efficacy to AZA and AZEVEN. And it looks like if the consistency that we saw from mechanism to lab to clinic works the same way in the leukemia triplet that it's worked everywhere else we've tested it. The part that I'd say really merits some exploration is making sure, knowing that the toxin is high in ACE events, that we don't add to it. We don't have any reason to believe that it would be that adding a mover would make it less tolerable.

Speaker Change: Of course, it makes sense that if you looked at our our preclinical data and we've got a really nice outline of the preclinical data in our corporate deck.

Speaker Change: It's very clear that from an efficacy perspective.

Speaker Change: In the lab, we were able to add efficacy to Asia is a van.

Speaker Change: And it looks like.

Speaker Change: If the.

Speaker Change: <unk> see that we saw from mechanism to lab to clinic works the same way in the leukemia triplet that it's worked everywhere else we've tested.

Speaker Change: We would expect to see that the the part that I would say really merits. Some exploration is making sure knowing that the taxes is high in ace event that we don't add to it. We don't have any reason to believe that it would be that adding a move started would make it.

Speaker Change: Less tolerable.

Jim Dentzer: Based on what we know, there is no overlapping safety profile. However, as we said, half of all patients that go on to Azoban have difficulty tolerating it. We, the first thing we're gonna look for as we add our drugs to Azoban is to make sure we're not exacerbating those, and of course, efficacy is what you always look for, but you know, first things first, let's make sure that we've got a drug that's tolerable in common. And what are your thoughts on the maintenance setting in Yale Law?

Speaker Change: Based on what we know there is no overlapping safety profile.

Speaker Change: Or as we said half of all patients that go onto he's been have difficulty tolerating it.

Speaker Change: First thing, we're going to look for as we add our drugs to as bad as to make sure we were not exacerbating those toxicities.

Speaker Change: Of course that efficacy you always look for it but.

Speaker Change: First things first let's make sure that we've got a drug that's tolerable in combination.

Speaker Change: And what I guess thoughts on the maintenance setting.

Jim Dentzer: Are you collecting any data points that could potentially maybe support off-label use? Well, obviously, off-label use is something that happens, but companies don't target that. What we do look for is, do we have a drug that, first and foremost, is faith, second a compelling and unique efficacy profile so that we can provide a measure of efficacy that you can't get from other drugs? And then third, to your point, you want to make sure you've got a drug that can be taken chronically for long periods of time. You know, some of the indications we're going after, like AML, are fairly aggressive, but others, like Wollingstrom's, are quite indolent. We have a patient that's been on drugs for, I believe, over four years.

Speaker Change: Now are you collecting any data points that could potentially.

Speaker Change: Maybe support off label use.

Speaker Change: Well, obviously off label, we use is something that that that happens, but companies don't target that what we do look for is do we have a drug that first and foremost is safe.

Speaker Change: Second.

Speaker Change: As a compelling and unique efficacy.

Speaker Change: Profile. So that we can we can provide a measure of efficacy that you can't get from other drugs.

Speaker Change: And then third to your point you want to make sure you've got a drug that can be taken chronically for long periods of time, you know some of the indications we're going after like AML or are fairly aggressive, but others like Walgreens firms are quite indolent.

Speaker Change: We have a patient that's been on drug for a bit.

Speaker Change: We've over four years now so we've got a great track record. These are still early days of drug development from a a circuit.

Jim Dentzer: So we've got a great track record. These are still the early days of drug development for MSU surgeons, but I think so far, we've been able to check all three boxes. The drug looks, in almost 200 patients tested, to have a really good safety profile. It looks as though it does provide in humans the same kind of clinical efficacy that we were seeing in the lab. And it looks as though you can take this drug over a long period of time in a maintenance setting, and that, of course, that's the trifecta that you hope for as a drug. Thank you, comes from Yale Jen of Laidlaw and Company. Please go ahead. Good morning, and thanks for taking the questions.

Speaker Change: But I I think so far we've been able to check all three boxes the drug.

Speaker Change: Looks in almost 200 patients tested to have a really good safety profile.

Speaker Change: It looks as though it does provide in.

Speaker Change: Humans, the same kind of clinical efficacy that we're seeing in the lab and it looks as though you can take this drug over a long period of time.

Speaker Change: In the maintenance setting.

Speaker Change: And that's of course, that's the Tri sector that you hope for us as drug developers.

Speaker Change: Thank you.

Speaker Change: Yep.

Speaker Change: Next question comes from Yale Jen of Laidlaw <unk> Company. Please go ahead.

Yale Jen: Good morning, and thanks for taking the question.

Jim Dentzer: Uh, Jim, you have talked about that you would be interested in moving to NDS, a high-risk MDS as the second line, but you're waiting for the Verona study readout. To your best knowledge, when do you think that might happen, and if it takes place sometime in the future, and what's your plan at this point? Yeah, thank you, Yael. Appreciate the question. So you're exactly

Yale Jen: Jim you have talked about that are you.

Yale Jen: Be interested to move to India.

Yale Jen: High risk Mds second line, but you're waiting for the Verona study readout.

Yale Jen: Just to your best knowledge, when you think that might happen and.

Yale Jen: Well.

Yale Jen: And if that if that take place sometime in the future and what what's still plan had disclosed.

Speaker Change: Yeah. Thank you yeah I appreciate the question, so you're exactly right and the opportunity in Mds looks terrific clinical data that we've put out so far it looks as though in M. D. S. Just as it did in AML and just as it has been in lymphoma.

Jim Dentzer: And the opportunity in MDS looks terrific. The clinical data that we've put out so far looks as though in MDS, just as it did in AML and just as it has in lymphoma, it appears as though this drug has a single agent, is active, and it provides unique and compelling anti-cancer activity.

Speaker Change: It appears as though this drug as a single agent.

Yale Jen: Is active it provides unique and compelling anticancer activity, we would really like to do in Mds, what we're doing in leukemia, which is go frontline in combination with standard of care and see whether or not we can.

Jim Dentzer: We would really like to do in MDS what we do in leukemia, which is go frontline in combination with standard of care and see whether or not we can provide benefits. But can this really add to the effectiveness of standard of care? Well, in AML, we know what the standard of care is. It's H of M. I think MDS development has just gone a little slower with AZN. A lot of people were expecting it to read out this past ASH.

Jim Dentzer: Provide benefit can this really add to the effectiveness of standard of care.

Yale Jen: Well in AML, we know what the standard of care as it takes events.

Yale Jen: I think Mds development has just gone a little slower with ease of them.

Yale Jen: A lot of people were expecting it might've read out this past ash now people are looking for ASKO to be Frank we don't know any more than you do.

Jim Dentzer: Now, people are looking for ASCO. To be frank, we don't know any more than you do of when those are going to read out, but we do expect it's imminent. And the answer is that standard of care in MDS is going to be either AZA or the AZN doublet. If Verona reads out positively, it's AZN.

Jim Dentzer: Those are going to read out, but we but we do expect the dividend and the answer is the standard of care in Mds is going to be.

Jim Dentzer: Either Asia or the ease of end up with if a rona retail positively it stays event if it reads out negatively at visa.

Jim Dentzer: If it reads out negatively, it's AZA. And what we want to know is which of those two wins, if you like, so that we can then initiate a combo, whether it's a doublet or a triplet, to see whether we can add benefit to that population in the frontline setting. So, we're eagerly anticipating it as you are, and as soon as we have those results, we'll be looking to initiate a frontline study in combination. Okay, great. That's very helpful.

Jim Dentzer: And what we want to know is which of those two wins. If you like so that we can then initiate a combo, whether its a doublet or triplet to see whether we can add.

Jim Dentzer: Add benefit to that population in the frontline setting. So we're eagerly anticipating it as you are and as it as soon as we have those results will be looking to initiate a frontline study in combination in MBS as well.

Speaker Change: Okay, Great that's very helpful.

Speaker Change: My second question here.

Jim Dentzer: And my second question here is that earlier we thought we were expecting that you guys might conduct a meeting with FDA to talk about the next stage of development after the AML data. Do you anticipate this meeting could happen later, much later this year, or do you anticipate this potentially being 2025? So I really can't speak on behalf of the FDA about how quickly we're gonna have that meeting. We're, of course, very interested in having it as soon as possible. I think we have the kind of drug that the FDA should likely be as interested in as all of our investigators are. And that is, we've got a drug that has a great safety profile, that really seems to add efficacy wherever we're testing it, and may be able to provide benefit in areas like second-line PCNFL where there are no approved drugs. The FDA ought to be receptive to that.

Jim Dentzer: Earlier, we thought we were sort of expecting that you guys made.

Jim Dentzer: And have a meeting with FDA to talk about the next stage of development after the.

Jim Dentzer: Oh AML data.

Yale Jen: Do you anticipate that meeting could happen later much later this year or you anticipate to potentially be a 2025 of them.

Jim Dentzer: So.

Jim Dentzer: I really can't speak on behalf of the F. D. A how quickly we're going to have that meeting we're of course very interested in having it as soon as possible.

Jim Dentzer: You know I think we have the kind of drug that the FDA should likely be as interested in it's all of our investigators are and that is we we've got a drug that has a great safety profile.

Jim Dentzer: That really seems to add efficacy wherever we're testing it and may be able to provide benefit in areas like.

Jim Dentzer: Second line P. C N S out where there are no drugs.

Jim Dentzer: Proved we actually ought to be receptive to that so as soon as we can get a sufficient number of patients together and it's probably in that 10 to 20 range.

Jim Dentzer: So as soon as we can get a sufficient number of patients together, and it's probably in that 10 to 20 range, and depending upon what kind of results we're getting, if the results are consistent moving forward with what we've seen in the past, we'd be looking to have a meeting with FDA as soon as we can. And then, of course, as you know, the FDA has got a lot of guidelines about when you apply and how quickly they hold those meetings.

Jim Dentzer: Depending upon what kind of results, we're getting if the results are consistent moving forward.

Jim Dentzer: To what we've seen in the past we'd be looking to have a meeting with FDA as soon as we can and then of course as you know the FDA has got a lot of guidelines about when you apply and how quickly they have those meetings, but we'd be somewhat subject to the fda's scheduling on their end, but we look really forward to being able to tell you when we when we've got that call on the docket.

Diantha Duvall: But we'd be somewhat subject to the FDA's scheduling on their end. But we look really forward to being able to tell you when we've got that call on the docket so that we can push these drugs forward as quickly as possible. Okay, great. Maybe I just want to tackle one last housekeeping question. I know you guys do not typically give guidance in terms of operating expenses, but could you give a more directional sort of suggestion in terms of operating expenses this year, 2024, compared to 2023?

Diantha Duvall: So that we can push for these drugs as quickly as possible.

Diantha Duvall: Okay, great and maybe just tackle one loss.

Diantha Duvall: Taking questions.

Speaker Change: No you got do not typically give guidance in terms of the operating expenses.

Speaker Change: But could you get more directionally the rational for that.

Speaker Change: Suggestion in terms of.

Speaker Change: Operating expenses this year.

Speaker Change: 2024, comparing 2003 and thanks.

Diantha Duvall: And thanks. Yeah, why don't I ask Dan to chime in on that? Thanks, Jim. So yeah, I mean, we believe that our operating expenses are going to remain relatively consistent as, as we've guided the 56 point, the 56 million in cash gets us into 25. So that gives us a burn rate of kind of 10 to 12, may peak up to 13, depending on the timing of some manufacturing and other things that tend to be a little bit more chunky.

Dan: Yeah, why don't I start.

Dan: Panther to chime in on that.

Dan: Thanks, Tim So yeah, I mean, we believe that our operating expenses are going to remain relatively consistent.

Dan: As we've guided at $56.

Dan: The $56 million of cash gets us into 25, so that gives us the burn rate in a kind of 10 to 12 may pick up to 13, depending on timing of.

Dan: Some some manufacturing and other things that tend to be a little bit more chunky, but I think you should expect it to be fairly consistent year over year.

Jim Dentzer: But I think you should expect it to be fairly consistent year over year. Okay, great. Thanks a lot and congrats on the development. I look forward to the data readout. Thank you. The next question comes from Bill Johnagiri of Truist Securities. Please go ahead. Hi, congratulations. Thanks for taking my questions. We were wondering if you could tell us anything about strategic or partnership interest at JPM from your end. And then also, for the triplet study in AML, for the patients you're enrolling, could you just remind us what the bars would be for that one?

Speaker Change: Okay, great. Thanks, a lot congrats all the development and look forward to the data readouts.

Speaker Change: Thank you.

Jim Dentzer: Yeah.

Bill Johnagiri: The next question comes from Bill John and Gary of Truth Securities. Please go ahead.

Bill Johnagiri: Hi, congratulations thanks for taking my questions. We were wondering if there were any.

Bill Johnagiri: Could you if you could tell us anything about strategic partnership.

Bill Johnagiri: Interest at J P M from year end.

Bill Johnagiri: And then also for the triplet study in AML.

Bill Johnagiri: For the patients you're enrolling could you just remind us.

Bill Johnagiri: The bars would be for that one.

Jim Dentzer: Thank you. Sure. Thanks, Phil.

Jim Dentzer: Sure.

Jim Dentzer: So, as you can imagine, the interest that we've seen on the partnering side kind of mirrors the interest that we've got on the investigator side in participating in our trials. And we, of course, are always having conversations with potential partners. And at some point, you know, I think many people would like to imagine that we could go broadly with this drug everywhere where we think it could work. So that's across lymphoma in areas wherever BTK gets used, in leukemia, AML, and MDS in a frontline setting, and now in solid tumors. We've just started in melanoma, but as I mentioned, there are a number of other solid tumor indications that have been studied with our drug by NCI and academic centers. And Curis just can't afford, we're too small; we can't afford to run studies in all those areas.

Bill Johnagiri: Thanks, though so as you can imagine the the interests that we've we've seen on the partnering side kind of mirrors. The interest that we've got in the investigator sided participating in our trials and we of course are always having conversations with potential partners and at some point.

Jim Dentzer: Many people would like to.

Jim Dentzer: We'd like to imagine that if we can go broadly with this drug.

Jim Dentzer: Everywhere, where we think it could work so that's a cross lymphoma in areas wherever be teekay gets used in leukemia, AML and Mds in a frontline setting and now in solid tumors. We've just started in melanoma, but as I mentioned there are a number of other solid tumor indications that have been studied with our drug <unk>.

Jim Dentzer: NCI in academic centers.

Jim Dentzer: And curious just can't afford we you know we're too small we can't afford to run studies in all those areas at some point, it's going to make sense to turbocharge those clinical efforts with the help of a partner both with bank book and manpower.

Jim Dentzer: At some point, it's going to make sense to turbocharge those clinical efforts with the help of a partner, both with BankBook and Manpower. You know, going forward, I think it's unlikely that we're going to strike a deal as we did in melanoma where we don't have to give up any rights and we get, just by providing the drug, we get data. But I think at some point, that will make sense

Jim Dentzer: You know going forward I think it's unlikely that we're going to strike a deal as we did.

Jim Dentzer: In melanoma, where.

Jim Dentzer: We don't have to give up any rights and we get just providing drug we get data.

Jim Dentzer: But I think at some point that will make sense and I would say, where we're not giving guidance on timing for that.

Jim Dentzer: And I would say we're not giving guidance on timing for that, but I'd say stay tuned. You know, this looks to be a really compelling drug, and Curis is not the only company that's recognized. And could you remind me, Bill, the second part of your question? Yes, about the triplet.

Jim Dentzer: But I'd say stay tuned.

Jim Dentzer: This it looks to be a really compelling drug and curious if not the only company that's recognized that.

Jim Dentzer: And could you remind me bill, but the second part of your question.

Bill: For the yeah. The triplet so I am not really sure what the patients look like.

Jim Dentzer: So I'm not really sure what the patients look like and the eligibility criteria are, so I was wondering if you could just tell us what the bar would be for success there and, overall, give us some benchmarks. Right, thank you. Yeah, I think, as I mentioned to Lee Watson at Cancer, I think the bar really is a safety bar in the early days. You know, we are cognizant that the doublet of Azazan is difficult for patients to tolerate. When we look at the drugs we're combining with, whether it's Azazan or Ibrutinib, for that matter, these are all drugs that are effective, but their safety profiles are tough.

Jim Dentzer: And then the eligibility.

Jim Dentzer: Really the criteria. So I was wondering if you could just tell us what the bar would be for success there and.

Jim Dentzer: Just like overall the benchmarks.

Speaker Change: Right. Thank you Yeah, I think as I mentioned to lead to the Wassa get cancer I think the the bar really is a it's a safety bar in the early days and we are cognizant that.

Jim Dentzer: The.

Jim Dentzer: The doublet of <unk> event is difficult for patients to tolerate.

Jim Dentzer: When we look at the drugs, we're combining with whether it's as a banner ibrutinib for that matter.

Jim Dentzer: These are all drugs that they're effective but there their safety profiles are tough.

Jim Dentzer: And so the first order of business, if we're going to combine them with those, we want to make sure that we don't take a difficult regimen to tolerate and make it worse. So, first things first, there's no reason to believe we have an overlap of safety profiles, but we need to test that out in patients and make sure that that's the case. It's easily the thing we're looking for first. Now, of course, whenever you're looking for safety, once you pass that hurdle, you're gonna be looking for signs of efficacy, and we're gonna wanna be able to replicate in the clinic with the triplet what we've been able to do in all of our other studies today, and that is, recapitulate the preclinical experience and show that adding M And if we can do that, I think that's a home run. So first things first, safety, but of course, we're gonna look for efficacy as well.

Jim Dentzer: And so the first order of business, if we're going to combine with those we want to make sure that we don't take a difficult regimen to tolerate it may get worse.

Jim Dentzer: First things first there's no reason to believe we we have an overlap of safety profile, but we need to test that out and patients and make sure that so that it's easily the thing we're looking for now.

Jim Dentzer: Now of course whenever you're looking for safety once you pass that hurdle youre going to be looking for signs of efficacy and we're going to want to be able to see that we can replicate in the clinic.

Jim Dentzer: With the triplet, what we've been able to do it.

Jim Dentzer: In all of our other studies to date and that is recapitulate, the preclinical experience and show that adding animal research it.

Jim Dentzer: That did a dressing this novel driver of cancer in Iraq for that addressing that target does yield incremental efficacy above and beyond current standard of care and if we can do that I think that's that's the homerun. So first things first safety, but of course, we're gonna look look for efficacy as well.

Jim Dentzer: Hopefully, that's helpful. wonderful. Yeah. And I guess one last one. I just want to verify, make sure I'm not thinking about this incorrectly.

Speaker Change: Hopefully that's helpful.

Speaker Change: Yeah, and I guess, one last one just I just wanted to clarify make sure I'm not thinking about this correctly. It seems like you're already hitting the duration bar in CNS lymphoma, right, we just need that data set to grow.

Jim Dentzer: It seems like you're already hitting the duration bar in CNS lymphoma, right? We just need that data set to grow. Yeah, I think we're exactly right. I think the data set looks fantastic. In fact, it looks quite a bit better than we would need.

Jim Dentzer: Yeah, I think it's exactly right, but I think the data set looks fantastic insight.

Jim Dentzer: It was quite a bit better than we would need.

Jim Dentzer: But it's early days standing up five. So, as we go to ten, and then to twenty patients, you know, as I said, I think what we need to be able to show... If you had 20 patients with primary CNS lymphoma that you were treating that had failed high-dose methotrexate and chemo, these days, they're going to go on BTK, they're going to go on iBru

Jim Dentzer: But it's early days, it's been a five so as we go to 10, and then to 20 patients.

Jim Dentzer: As I said I think what we need to be able to show.

Jim Dentzer: If you had 20 patients with primary CNS lymphoma.

Jim Dentzer: That you were treating that were that had failed.

Jim Dentzer: Hi, Joe Smith of trucks and chemo.

Jim Dentzer: They're gonna go I'd be teekay, they're gonna go on Ibrutinib.

Jim Dentzer: You would expect four of those 20 patients to get a response based on the largest study that's been done on Ibrutinib monotherapy CR rate of 19.

Jim Dentzer: You'd expect four of those 20 patients to get a response. Based on the largest study that's been done on abrutinib monotherapy, the CR rate is 19. So let's round up a little bit, call it 20. You'd need four CRs out of 20. In our case, we're three of five. We need to add 15 more patients and get one more CR, just to match the earlier line, because remember, all of our patients have failed ibrutinib. You'd expect zero out of 20 if you re-challenge them with ibrutinib.

Jim Dentzer: So lets round up a little bit call. It 'twenty you'd need for Crs out of 20 patients.

Jim Dentzer: In our case, where three of five.

Jim Dentzer: We need to add 15, more patients and get one more C. R.

Jim Dentzer: Just to match the earlier line.

Jim Dentzer: Because remember all of our patients who have failed Ibrutinib you would expect zero out of 'twenty. If you re challenge them with Ibrutinib.

Jim Dentzer: So in our case, if we can match that prior line, it gets 4 out of 20 or one more CR out of the next 15 patients. I think we've got a really compelling discussion to have with the FDA, and I think, frankly, our odds are pretty good at that. Great, thank you. You bet.

Jim Dentzer: So in our case, if we can match that prior line it gets harder to 'twenty or one more see are out of the next 15 patients.

Jim Dentzer: I think we've got a really compelling discussion to have with FDA and I think frankly, our odds are pretty good at that.

Speaker Change: Great. Thank you.

Jim Dentzer: You bet.

Jim Dentzer: 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, Jim Dentzer, for any closing remarks. Thank you, Andrea. And thank you everyone for joining today's call. And, as always, thank you to the patients and families participating in our clinical trial, to our team at Curis for their hard work and commitment, and to our partners at Origin and the NCI for their ongoing help and support. We look forward to updating you again. Operator

Speaker Change: Thank you.

Jim Dentzer: 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, Jim Dentzer for any closing remarks.

Jim Dentzer: Thank you Andrea and thank you everyone for joining today's call and as always thank you to the patients and families participating in our clinical trials to our team of curious for their hard work and commitment and to our partners at origin and the NCI for their ongoing help and support.

Speaker Change: We look forward to updating you again soon.

Jim Dentzer: Operator.

Speaker Change: The conference has now concluded. Thank you for attending today's presentation and you may now disconnect.

Operator: The conference is now concluded. Thank you for attending today's presentation, and you may now disconnect. Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. www.yale.edu.au

Operator: [music].

Operator: Yes.

Operator: [music].