Curis Inc (CRIS) 2020 Q2 法說會逐字稿

Good afternoon, and welcome to Curis' Second Quarter 2020 Earnings Call. (Operator Instructions) Please note, this event is being recorded.

I would now like to turn the conference over to the company's Chief Financial Officer, Bill Steinkrauss. Please go ahead.

Thank you, and welcome to Curis' Second Quarter 2020 Earnings Call. Before we begin, I would encourage everyone to go to the Investors section of our website at www.curis.com to find our second 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. These statements are subject to certain risks and uncertainties, and actual results may differ materially. For additional details, please see our SEC filings.

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 Curis' CEO, Jim Dentzer. Jim?

Thank you, Bill. Good afternoon, everyone, and thank you for joining us today. As many of you know, our mission at Curis is to develop the next generation of targeted cancer therapies to meaningfully improve and extend patients' lives. Our novel pipeline is driven by our team's expertise and ability to identify untapped targets in oncology that we believe have significant potential to address unmet patient need.

In the second quarter, we executed against both clinical and financial goals, making significant progress toward key targets for the year. We advanced dose escalation in our ongoing study of CA-4948, our IRAK4 program, in patients with relapsed or refractory non-Hodgkin's lymphoma or NHL. We initiated a second IRAK4 study in patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS. Also in the second quarter, we received FDA clearance to proceed on our investigational new drug application for CI-8993, our monoclonal anti-VISTA antibody.

Lastly, we also completed a significant financing transaction with several fundamental health care investors. It was a very eventful quarter for Curis. And in aggregate, these accomplishments set us up for exciting data catalysts later this year and continued momentum as we look to 2021. We're moving full steam ahead at Curis, and I look forward to building on this progress in the third quarter.

With that, let's jump into our clinical development programs, starting with our small molecule IRAK4 kinase inhibitor, CA-4948. As a reminder, we are currently evaluating CA-4948 in an ongoing Phase I dose escalation study for the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma or NHL, including patients with diffuse large B-cell lymphoma, Waldenström's macroglobulinemia and Oncogenic MYD88 mutations. In this Phase I study, we are currently evaluating patients being treated with 300 milligrams twice daily of CA-4948 after observing clear dose response and tumor reductions at previous dose levels. The pace of enrollment slowed in the second quarter as many clinical sites temporarily halted enrollment due to the COVID-19 pandemic. Fortunately, following new guidance and protocols, several of our Phase I study sites have reopened and are actively enrolling new patients. So while the data are not yet mature enough for us to declare a recommended Phase II dose today, we are confident we will be in a position to provide updated safety and efficacy data as well as finalize the recommended Phase II dose by the end of this year.

That said, the tumor reduction data we have seen so far are very encouraging. It is with these data in hand that we are excited to announce today our plan to initiate the combination study of CA-4948 with ibrutinib, the market-leading BTK inhibitor. In preclinical models, both IRAK4 and BTK inhibition have been shown to provide significant anticancer benefit. As one might expect, given their different mechanisms of action, they also appear to be highly synergistic. We and our clinical investigators are eager to see if this preclinical efficacy in-combination therapy translates to the clinic as well as the single-agent efficacy data has. With today's announcement, we are initiating work with our clinical sites and the FDA and expect to begin enrollment in a Phase I study of CA-4948 in combination with ibrutinib before year-end.

Now let's move to leukemia, our study in CA-4948 in patients with relapsed or refractory AML and high-risk MDS, including those with spliceosome mutations driving expression of the oncogenic long isoform of IRAK4. Last month, we announced the dosing of the first patient in our open-label Phase I dose escalation study of CA-4948 monotherapy in these patient populations. We have been eager to start this study ever since the seminal presentation of Dr. Amit Verma and Dr. Daniel Starczynowski at the ASH conference last year, in which they identified specific spliceosome mutations as drivers of disease by causing the expression of the long isoform of IRAK4.

While the short isoform of IRAK4 is normal, they demonstrated that the long isoform is oncogenic. Further, they demonstrated that blocking IRAK4 with a treatment of 4948 dramatically reduced the formation of leukemic blasts. Their work changed the landscape of AML and MDS by identifying IRAK4-L as the first and only known driver of disease that affects over half the population of patients with AML and MDS. With the findings of Dr. Verma and Dr. Starczynowski in hand as well as the preliminary data from our NHL study, we worked quickly with our clinical investigators and the FDA to design a study of CA-4948 in the AML and MDS population. And we are pleased to have dosed our first patient just 6 months later. This Phase I dose escalation study is enrolling a minimum of 3 patients at each dose level starting with 200 milligrams twice daily. As I mentioned earlier, we are excited to be starting this study at a potentially therapeutic dose level following the FDA's sign-off, as 200 milligrams twice daily was determined to be both safe and capable of achieving encouraging biologic activity and clinical efficacy in our Phase I NHL study.

The primary objective of this study is to determine the maximum tolerated dose and recommended Phase II dose of CA-4948 based on safety and tolerability, dose-limiting toxicities and pharmacokinetic and pharmacodynamic findings. We could not be more excited to have this study underway and we look forward to reporting initial data by the end of this year.

Now I'd like to turn to our VISTA program and our first-in-class monoclonal anti-VISTA antibody, CI-8993. This is a target we're really excited about. When activated, VISTA plays a critical role in suppressing T cell activity. Conversely, blocking VISTA has been shown in preclinical studies to prevent T cell suppression and thereby reactivate antitumor immune function. We also see potential in targeting VISTA in combination with a PD-1, PDL1 or even a CTLA-4 inhibitor, as preclinical studies suggest that blocking VISTA significantly improves the efficacy of those checkpoint regulators.

As many of you remember, we previously developed a small molecule that targeted PDL1 and VISTA. While that small molecule was active, it did not produce efficacy competitive with the monoclonal antibodies in development at that time in our target population. We believed this was probably for 2 reasons: First, as a large molecule, a monoclonal antibody provides complete coverage of a receptor across multiple binding regions. By comparison, a small molecule interrupts only 1 or 2 contact points on a target receptor. Second, monoclonal antibodies tend to firmly wrap around a receptor, almost like Velcro, as opposed to a small molecule, which continually bounces on and off its target.

For these reasons, we began a search last year for the best IP, the best library of drug candidates and the deepest understanding of VISTA biology. In ImmuNext, we found a partner with all three. And in January of this year, we entered into an option and license agreement with them for the development and commercialization of CI-8993 and went immediately to work on developing it. In June, just 5 months later, the FDA cleared our IND application for CI-8993, making it the only anti-VISTA antibody currently in development to enter testing in humans.

We are pleased with the interest and excitement we've received from the clinical community on this program, and we believe CI-8993 has the potential to be a game-changing cancer therapy. We look forward to initiating a Phase I study of CI-8993 in patients with solid tumors later this year.

To wrap up, we're very excited about our clinical progress so far this year. We hope the next few months will bring us even closer to developing meaningful therapies to patients battling cancer.

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

Thank you, Jim. For the second quarter of 2020, Curis reported a net loss of $6.7 million or $0.17 per share on both a basic and diluted basis as compared to a net loss of $7.2 million or $0.22 per share on a basic and diluted basis for the same period in 2019. Revenues for the second quarter of 2020 were $2.4 million as compared to $2.1 million for the same period 2019. Revenues for both periods comprised primarily of royalty revenues recorded on Genentech and Roche's net sales of Erivedge.

Operating expenses for the second quarter of 2020 were $7.8 million as compared to $8.2 million for the same period 2019. Costs of royalty revenues were $0.1 million for both the second quarter 2020 and 2019. Research and development expenses were $5.3 million in the second quarter of 2020 as compared to $5.6 million for the same period in 2019. The decrease was primarily attributable to reduced clinical trial costs related to CA-170 and fimepinostat.

General and administrative expenses were $2.4 million in the second quarter of 2020 as compared to $2.5 million for the same period in 2019. The decrease was driven primarily by lower stock-based compensation, legal and professional services fees, partially offset by higher occupancy costs. Other expense net was $1.3 million for the second quarter of 2020 as compared to $1.1 million for the same period in 2019. Other expense net primarily consisted of imputed interest expense related to future royalty payments.

As of June 30, 2020, our cash, cash equivalents and investments totaled $23.6 million, which includes net proceeds from our $17.5 million registered direct offering that closed in June. As of June 30, 2020, there were approximately 50.6 million shares of common stock outstanding. We expect that our existing cash, cash equivalents and investments should enable us to maintain our planned operations beyond our end-of-the-year data catalysts and into the first half of 2021. Note that our forecast does not include any potential proceeds from our stock purchase agreement of up to $30 million with Aspire Capital.

With that, I'd like to open the call for questions. Operator?

(Operator Instructions) The first question comes from Alethia Young with Cantor.

A couple of questions I have here. One, just on 4948 and at the end -- you have data coming out at the end of the year. I guess maybe you can help us like think about maybe how many people that might be. And what is kind of the impact of COVID? Or is it just that you kind of need more data to kind of appreciate what the dose is?

And then my second question is just around the combination with ibrutinib and how you're thinking about what will be the right dose level to use there.

And then my third question is, what are the rate-limiting steps related to like starting the anti-VISTA program in the second half of the year? Are there any or do you kind of expect that you're in the final stretch to doing that?

Sure. Alethia, thanks for calling in. So 3 questions, I think your update that we said that's getting delayed by COVID, the combo and then, of course, the anti-VISTA rate-limiting factors.

So the enrollment in the lymphoma study, you're exactly right. We did have an impact on COVID-19. Some of the sites did shut down entirely. The good news is they have come back up and started to enroll again. So while we're only looking for a handful of extra patients, we have got some new patients on. And frankly, we just need to have those patients be on drug long enough to read out the data, so just to let the data mature. We do have confidence based on the patients that we haven't been able to enroll since they've reopened, that we will be in a position to finalize that Phase II dose by the time we get to year-end. But unfortunately, yes, the break with COVID impacted us just like it impacted a lot of folks in the industry.

On the combo study, could you remind me your second question again?

You said -- I just wanted to know how you thought about finding the right dose there for that. I know -- I thought you were using kind of some of the 4948 work with the other sites to inform your dose.

So it would have been a no-brainer if we had the Phase II dose identified in lymphoma. We would just start there. I think the issue with the combo study was we now know enough for sure that we're going into Phase II. We know enough about that data, that the data looks good. The question was really, well what dose is the right dose? And we had 2 choices. One was delay until we finalized the Phase II dose and let all the data mature. Or since we know we're ready to go, and we know 200 works, let's just get this study up and running, get them on the dose that's therapeutic, which is 200. And if they clear that dose, we'll just dose escalate, just as we have been doing on the monotherapy side. So sorry, really, that's just the answer on the combo side.

On VISTA, there really is no rate-limiting factor. I would say the discussions with the FDA were frankly more productive and more effective and faster than we anticipated. So we are moving at a breakneck pace to get our sites open as fast as possible. So it's really now just the blocking and tackling of working with the sites now that they're also up post-COVID to get them to -- through all of their processes and start enrolling patients in that study.

The next question is from Soumit Roy with JonesTrading.

Congrats on pushing through the ibrutinib combo in NHL, really powering the asset. Wanted to get your sense on following this monotherapy trial with 4948. Are you seeing -- or are the physicians enrolling more non-GCB patient type? Or is that a focus, you would focus on more in the ibrutinib combo trial? And if you can give us some color of what line patients you are seeing. Are they are -- what percent are transplant relapse or naive? Some kind of color on the patients in NHL.

Sure. Thank you, Soumit. First and foremost, thanks for calling in. We appreciate your interest. So in terms of the patients being enrolled, I would say there's certainly a wide mix of indications. We don't yet have the data back. We will have the data back eventually, certainly by the time we report out of MYD88 mutations. We're very interested in knowing that as well. But we've been pleased that there's been a broad swath, a broad sampling of patients across multiple indications to put into the study. They are relapsed/refractory patients. We're finding that they're on average about 3.5 lines of prior therapy before they come in. So they are pretty sick. But of course, we're encouraged that interest level in getting them in is high, that the dose response has been so clear. And we're very interested in knowing as we get the final data back on MYD88 alterations, where the data tend to correlate, even though it's a small number of patients, I think every little bit of information is going to be very helpful for us as we go forward. Go ahead.

The ibrutinib combo trial, would you focus on non-GCB type? Or would you leave it wide open to the physician's description?

Yes. I think -- so there's 2 thoughts. First, I think the intent of the study is really building on the preclinical data that we have. So the -- you may remember that the preclinical data that we have on a slide in our corporate presentation shows that as a single agent, IRAK4 and BTK inhibition are both really powerful. It's in combination that they appear to be very synergistic and, of course, more powerful than either on its own. So with that thought in mind, we're really looking to target patients who would otherwise be on ibrutinib. So any indication where ibrutinib gets used full out, we would expect to see synergy.

Now that said, while it's broadly open to those populations, anybody whose tumor type is at least partially driven by the toll-like receptor pathway should have an increased sensitivity to therapy and should respond even better. But we would expect, based on our preclinical data, that wherever we can find patients that are responding to BTK therapy, that adding 4948 to it should make it a more effective therapy. And that's really the population we're after.

Okay. And one question on the AML front. With Takeda in the high-risk MDS population, pevo, that has a high [risk points], fairly good response rate, a CR rate of 52%. Do you see the competitive landscape changing? And do you see the path to registration is not going to be as simple as an accelerator approval but rather be a full Phase III controlled arm trial? Do you see any change in strategy?

Yes. Actually, Bob, it might be a good idea for you to chime in on this one.

Yes. So that's a great question. We're launching this study that's in both AML and myelodysplastic syndrome. And each of these indications, excluding both high-risk and lower-risk MDS and AML, they do have different treatment algorithms. And we do anticipate that, that's going to evolve over time. But as Jim mentioned, one of the unique aspects about IRAK4 is that it is a key driver of the disease that was a (inaudible) so the drug directly targets that. So we think that this is going to be a key component of treating AML and MDS. We do know in terms of combining this drug with other drugs that are used [in treating AML] and MDS, that there are potential synergies. And so that would also factor into that. But yes, so we do see this evolving. But right now, there are a number of registrational pathways that we think are very viable.

Yes. Let me add 2 things to that, Soumit. So first, I know our phone seems to be cutting out. We did not plan our earnings call date for the date the hurricane would hit the Northeast. I appreciate your patience in trying to catch every other word as our individual phones do cut. But second, yes, just building on what Bob said. I do think the landscape in oncology, in general, and certainly, where we're headed, is always changing as new therapies come to light. One of the advantages of the small molecule 4948 is that it does combine well with multiple things.

The other thing is, as Bob mentioned and just to hammer home, in AML and MDS, in particular, while there are therapies that will prove effective in this space, there is only one driver of disease that impacts half the population, full stop. And we have the only drug in oncology currently in the clinic that directly targets that bad actor, that driver of disease. And that, of course, is IRAK4-L and 4948 targeting IRAK4-L. So while I do expect that there are other things that may work in this population, and I certainly hope that as an industry, we can generate lots of things that will help this population, I think the key drug that most of the investigators are looking to is the one that really targets the driver of disease, which is our drug.

(Operator Instructions) The next question comes from Yale Jen with Laidlaw & Company.

Congrats on the speedy sort of progression. It exceeds our expectation. So a couple of quick questions here. The first one is given the data at the time you want to release the data 4948, would ASH be the venue to contemplate?

Yes. So that's a great question. I think in general, our approach to releasing data is that we would ideally like to release data at a medical conference. So whenever the data mature to a sufficient level that it merits being released, we would, of course, look to the next appropriate medical conference where that can happen. If those dates coincide, terrific. If not, what we have done in the past, and we may well do in the future, is if data mature and there isn't an imminent medical conference, we may just release top line information and then follow that up with a more detailed presentation at a medical conference. But I like the idea of having our investigators frankly get on the stage and describe the data that they've been working with in front of their peers. And it provides the opportunity of a more objective view, which I think is always helpful. And frankly, given that all 3 of the data sets that we are looking at in the next 5 months are all cutting-edge, these are all really novel targets. These will be very exciting data sets. It's going to be very important to have our investigators speak to that at a very detailed level. So my hope is that as these data mature, a conference will be nearby. But if not, look to a short top line press release from us followed by that more detailed presentation.

Okay. Great. That's helpful. And for the 2 -- first of all, for the NHL, at this point, is the DLBCL more likely to potentially be the leading sort of indication you may explore going forward, for instance, in the combo study? Or you still want to do a sort of broad catch-in or type of study to cast the largest net?

Good question. So I'll answer that really in 2 ways. First, I think that the preclinical data that we have suggests that both BTK inhibitors and IRAK4, our IRAK4 inhibitor, are really looking to target NF-kappaB indirectly, so -- in all of the indications, whether it's DLBCL, whether it's MZL, MCL, CLL. Whatever ibrutinib gets used today, it's really targeting indirectly NF-kappaB. That's what our drug is looking to do as well. So those very same indications as a monotherapy would be the ones that we would pursue. It's the same indications that you'd see a BTK. But because it's a new mechanism of action, we did expect to see in the preclinical work, and we were very pleased to see it bore out that way, that the synergy is really there. These are 2 different mechanisms of action, 2 separate ways to get at NF-kappaB.

So with that thought in mind, our first goal was -- we have already established the scientific theory for why this new mechanism of action makes sense. We then developed the preclinical data set to support that this new mechanism of action would work. We have now shown an initial data set last December, and we're going to update that data set in the next 5 months with clinical data that shows the preclinical data holds up, that as a single agent, this drug shrinks tumors. The next logical step is, again, building on our preclinical data, and it says the combination is even better. So our view would be we want to pursue, both as a monotherapy and as a combo therapy, any indication where ibrutinib is approved. At monotherapy, it would provide an alternative. If, for whatever reason, someone wants to use an IRAK4 as opposed to a BTK, that option is there. We would see the preclinical data as very compelling about the combo therapy. So we're going to pursue as quickly and aggressively as we can, the prosecution of that clinical study, to see if that preclinical data is as predictive as all of the other data have proven to be. I hope that answers your question. I hope that was helpful.

It's very helpful. And maybe just a follow-up on that, which is that just if we look at DLBCL sort of landscape at the moment, that's little a bit cloudy, that -- would there be some other sort of indication if the [current] data read out to be the, let's say, the primary target for the future development, would that be a sort of easier path going forward for bearing fruits?

Yes. I think it's a little preliminary to say that just yet. It's exactly the right question, which is of all these different indications that we could pursue as either a monotherapy or a combination therapy in the lymphoma space, which one is going to gain priority and in terms of a regulatory strategy of trying to get to approval as fast as possible? And our view is we're on the brink of finishing up that Phase I dose escalation study. And with that data in hand and having done the analysis of all of the additional biomarker data that we're collecting, including the MYD88 data, we're going to want to try and identify which indications it clearly seems to benefit patients to have this drug available. And we're going to want to pursue all of those. But we're certainly going to want to prioritize those indications where we think we have the best and fastest shot at regulatory approval. And whether that is DLBCL or one of the other indications where you frequently find ibrutinib used remains to be seen just yet, but that's exactly the right question. And we will be looking to answer that question and address it publicly when this data is mature over the next few months.

Okay. Great. That's very helpful. Maybe 2 more quick questions. Number one, is that in the AML and MDS -- would that be more to AML or you will see both indications sort of equally and at this point, in terms of patient recruitment and try to see what sort of -- what will be the outcome from the current -- those dose escalating data at this point?

Sure. So I think we would treat -- I'm going to answer this one briefly, and then I'm going to ask Bob to jump in. So we're looking at both AML patients and high-risk MDS patients. Of course, with the AML patients, we're looking to address the disease outright. And with high-risk MDS, we want to make sure that these patients don't have disease that transforms to AML, right? We're looking to address both patient populations, and our study is open to enroll in both. Bob, would you like to jump in?

Yes. So both, as we talked about earlier, have different treatment algorithms as well. We do know, for example, that 4948 can reduce engraftment in AML leukemic blasts. So that was published by Amit Verma recently. And so we anticipate the direct impacts on the AML population. Additionally, with regards to MDS and especially high-risk MDS, you got some different end points there. One would be transitioned to [chronic] leukemia and, likewise, reduction in supportive care needs such as transfusions. So we look at these as 2 different paths as a way to see. Hopefully, while the monotherapy [activity] there, that may be sufficient. But we'll also look towards combinations with agents that are used in each of those situations.

Okay. Great. And then maybe I switch gear a little bit to CI-8993, and you guys anticipate some data come out late this year probably in the dose-escalating part of that. So is the key highlight we should pay attention to is the safety, in other words, if there's cytochrome release syndromes? And if that can be managed, then that will be a big win to start with.

That's exactly right. So this calendar year, the emphasis is going to be safety. Next calendar year would be efficacy. And just as a reminder, this lead molecule is one that has already been in the clinic. This -- J&J or Janssen, their subsidiary, originally licensed the IP from ImmuNext back in 2012. They then developed this antibody. It wasn't developed by Curis or by ImmuNext. It was developed by J&J, and then they put it into the clinic. And in very early subtherapeutic doses, they ran into CRS. They expected at the time, as we do, that you needed to get to somewhere around 0.5 to 2.0 mg per kg in exposure to get to efficacy levels. That was the therapeutic window. They never got to that window because both at 0.15 and at 0.3, they only had 1 patient at 0.3. They ran into cytokine release syndrome. And I think they were -- to be fair to them, back then, this is in the early days of CAR T, CRS was kind of scary. There were no guidelines for how to manage it. Those guidelines from the NCCN weren't even issued until 2018.

So I would say the oncology community as a whole has learned a lot about how to manage CRS. And we feel very comfortable that with the co-administrative therapies, steroids, tocilizumab, and in fact, some of the additional work that's been done at Dartmouth over the last 5 years since they got the rights back about how to modify the regimen of this particular monoclonal antibody to help desensitize patients, all of that information, I think, gives us a lot of confidence that we'll get to the therapeutic window. But we still need to prove it.

So I think this first step is we put together what I think is a very solid plan for how to manage CRS. We've taken advantage of the guidelines that have been issued since Janssen abandoned the program. We've taken advantage of the knowledge developed at Dartmouth, and frankly, the experience of the oncology community more broadly. We've run that by the FDA. The FDA is now comfortable, as we are, they're optimistic that we're going to be able to manage CRS effectively and get to that therapeutic window. But this calendar year is really -- that's the objective. Let's get a couple of patients on drug. We know that CRS should show up in the first few hours after treatment. We need to be able to say at year-end that we've had multiple patients on drug, that our plan for managing CRS seems to be effective and that we have a greater confidence level that we will be successful in escalating into the therapeutic window. And if we can do that, I think we're going to be in a very exciting place between now and year-end.

Okay. Great. And then maybe squeezing one more quick one for Bill. As I look at the second quarter operating expenses, which was lower than the first quarter and given the guidance, should we anticipate the operating expenses for the second half of this year will be -- sort of boost up a little bit more?

Yes. Thanks, Yale. I appreciate the question. Yes, so I think from a trend, one thing to remember that we did have some costs related to the option and license agreement in Q1 that didn't recur here in Q2. And we're also starting to see a little bit of the cost savings as we start to wind down some previous trials related to CA-170 and fimepinostat. But I think from a guidance, I still think that we will kind of remain consistent in the back half of the year. While we do add these programs, we're building off our existing infrastructure. So from a cash burn perspective, I still think $7 million to $8 million a quarter, that range, is the appropriate average. And obviously, some quarters will be a little bit less and some quarters may be a little bit higher. But I still feel that's the appropriate range for the rest of the year.

This concludes our question-and-answer session. I would like to turn the conference back over to the company's President and Chief Executive Officer, James Dentzer, for any closing remarks.

Thank you, operator, and thank you all for participating in today's call. I also want to thank the patients and families who continue to participate in our clinical trials, our team at Curis for their hard work and commitment and our partners at Aurigene and ImmuNext for their 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.