Ladies and gentlemen, thank you for standing by, and welcome to the Calithera Biosciences Fourth Quarter 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation there will be a question and answer session.

I would now like to hand the conference to your speaker today, Jennifer McNealey, VP, Investor Relations. Please go ahead, ma'am..

Thank you, Joelle. Good afternoon, everyone. Welcome to our year-end 2020 conference call. Joining me today are Susan Molineaux, our Founder, President and CEO; Keith Orford, Chief Medical Officer; and Stephanie Wong, Chief Financial Officer. We have issued our press release, and it can be accessed through our website at calithera.com..

Thank you, Jennifer. Good afternoon, everyone, and thank you for joining us today on our fourth quarter and year-end 2020 conference call. On behalf of the entire team, I'd like to say we hope that you and your friends and families remain healthy. 2020 was a challenging year for the nearly everybody as we face new challenges in public health.

Despite the challenges we faced, we are quite hopeful for the future. At Calithera, 2020 was a year of execution. We successfully completed and reported results of our global randomized trial in renal cell carcinoma early in 2021, while advancing our pipeline of novel therapeutics.

We want to thank all of our employees who have done an extraordinary job of maintaining a high level of professionalism, productivity and dedication at work, particularly towards helping us achieve our goal of reporting top line results of the CANTATA trial in January.

We're both appreciative and proud of our entire team for accomplishing a number of challenging goals. And while we are disappointed in the results of the CANTATA trial, we remain enthusiastic for the potential of glutaminase inhibition to be a novel approach to the treatment of cancer.

And we remain committed to our mission of being an integrated biotechnology company that develops novel small molecule onco-metabolism drugs, drugs that are targeting tumor and immune cell metabolism pathways for the treatment of cancer and other diseases.

By building a pipeline of novel therapeutic product candidates, we are creating multiple opportunities to positively impact clinical outcomes for patients and drive development programs towards commercialization.

We are continuing to develop telaglenastat, and we are enrolling the randomized KEAPSAKE trial in first line non-small cell lung cancer patients harboring genetic mutations in KEAP or NRF2. We also continue to evaluate telaglenastat in multiple indications, including investigator-sponsored trials..

Thank you, Susan. Let's begin with a more detailed update on telaglenastat, our glutaminase inhibitor in development for the treatment of first-line lung cancer in patients with KEAP1/NRF2 mutations. Mutations in the KEAP1/NRF2 pathway, which occur in an estimated 20% of non-small cell lung cancer patients, are associated with aggressive disease.

Numerous recent reports of clinical data have demonstrated that activation of this pathway, either through the loss of KEAP1 function or activation of NRF2, are associated with poor clinical outcomes among patients with non-small cell lung cancer receiving frontline standard of care therapies, including chemotherapy, immunotherapy and chemoimmunotherapy.

Preclinical models have shown that activation of the KEAP1/NRF2 pathway makes tumors dependent on glutaminase activity for growth and survival, making these tumors exquisitely sensitive to inhibition of glutaminase activity by telaglenastat.

The double-blind telaglenastat trial, known as KEAPSAKE, enrolled the first patient in September 2020 and will enroll approximately 120 patients. Eligible patients are newly diagnosed with Stage IV non-squamous non-small cell lung cancer with tumors that have the KEAP1 or NRF2 mutation.

Patients will be randomized to receive telaglenastat or placebo, in combination with pembrolizumab, carboplatin and pemetrexed. The study will evaluate the safety and investigator-assessed PFS of telaglenastat plus the standard of care chemoimmunotherapy regimen. We plan to share interim data from this trial in the second half of 2021.

We are also conducting an exploratory Phase Ib/II trial in collaboration with Pfizer combining telaglenastat with IBRANCE..

Thank you, Keith, and good afternoon, everyone. Detailed financial results for the fourth quarter and year-end of 2020 were included in today's press release. I will briefly review our results on this call. Calithera remains well capitalized.

Our cash, cash equivalents and investments were $115.2 million at December 31, 2020, which we believe will be sufficient to meet our current operating plan through 2022. R&D expenses were $71 million in 2020 compared to $76.3 million in 2019.

The decrease was due to a $6.2 million decrease in the 1158 program and a $3.8 million decrease in early stage research, partially offset by an increase of $2.7 million in the telaglenastat program and an increase of $2.0 million in the CB-280 program..

Thank you, Stephanie. And with that, Joelle, we're happy to open the line for questions..

Our first question comes from Mohit Bansal with Citi. Your line is now open..

This is James on for Mohit.

First question, any color on the enrollment progress for KEAPSAKE? I know we're on track for data later this year, but can you give us a little bit of a number at this point? Or is that still sort of a work in progress? And then related to KEAPSAKE, there was some recently some data from KRAS showing that STK11 mutation patients had a higher response to the KRAS inhibitor.

And I know that you guys have previously mentioned that the KEAPSAKE trial will have a good proportion of STK11 patients.

So I was wondering if Calithera looked at combining 11 stat with any KRAS inhibitors?.

Yes. James, this is Keith. In terms of enrollment, so as we said, we're planning to enroll and make public SEM data from the initial interim analysis later this year. I think enrollment has been, I would say, impacted by COVID.

I think all -- if you probably asked anyone, there has been some impact from COVID, but it's something we're working through, and we remain confident in our time line to be able to get to that -- to data on that interim analysis later this year. So definitely some impact, but something that we are working through.

In terms of the KRAS story, it's definitely one we're quite interested in. And that's sort of a, I guess, I would say, a work in progress, something we're looking into on our side.

But an area of a lot of interest, and I think there's been a couple of different reports on the impact of STK11 that actually between the two clinical KRAS inhibitors that were somewhat different, so that will be interesting to see how that plays out. But that definitely remains a combination of interest..

Our next question comes from Matt Phipps with William Blair. Your line is now open..

I guess just kind of a follow-up on that interim. I mean, this will be an interim for PFS, I see, right, as opposed to maybe just response rates.

And Keith, are you still thinking of PFS in the control arm of around 7 months? Or has there been any data lately there to change that assumption?.

So that -- so yes, in terms of -- Matt, in terms of the assumptions, we've actually been, for this population, so for the KEAP1 immune population, the data that have been reported in a few different places, put that probably the median somewhere in the 3- to 5-month range. So -- and this is in frontline.

So these patients do very poorly, and so that's what we're assuming. And yes, in terms of the data that we would be talking about, it's probably a combination of PFS as well as response rates. The data will be -- it's going to be an interim analysis and the data will still be kind of maturing.

So we're not going to be talking about fully mature data, but we do -- given the short expected PFS, median PFS for the control arm, we would expect to hopefully see some -- see some daylight between the 2 curves and be able to see a trend in the right direction there..

And any chance we see an update from that IBRANCE combo in pancreatic this year?.

We haven't guided on that. I think it's a little hard to say exactly when it will likely be this year or next. But that study really just started enrolling. So I think it's too early to say with certainty..

Our next question comes from Jonathan Chang with SVB Leerink. Your line is now open..

First question, can you provide your latest thoughts on how much and how mature the second half interim data set for KEAPSAKE could be?.

Jonathan, yes, in terms of the -- we're expecting somewhere in the range of 40 to 50 patients' worth of data by the end of the year. And I think that's kind of the ballpark. It's -- as we've talked about before, the analysis is not explicitly defined in the protocol with -- and having a specific sort of statistically driven endpoint or analysis.

It's not a futility analysis. It's not an early efficacy analysis. It's an administrative interim that allows us to have an early look at the data and react as appropriate, which could mean any number of things, reaching out to regulators, starting to prepare for a subsequent study. So that's the kind of the spirit of the interim..

And last question, how are you thinking about potential business development opportunities for your pipeline?.

Well, this is Susan, Jonathan. In general, we remain open to partnering opportunities as one of several ways to continue to develop our pipeline. We will read out this year the first data in cystic fibrosis patients.

And we have a clear picture of where we might go next, if that data look encouraging and there might be a partnering opportunity somewhere along the cystic fibrosis development time line. And as you know, we do have an earlier stage pipeline assets that are IND ready.

We have a CD73 small molecule oral inhibitor, and we also have an inhibitor for IL-4I1. And partnering is a possibility for those as well. And for telaglenastat, we'll wait and see what develops. But we're always open to partnering at the right time for the right reasons..

Our next question comes from Arthur He with H.C. Wainwright. Your line is now open..

So I have two. So regarding the KEAPSAKE study, maybe I missed.

Could you give us some color on the -- regarding enrollment? And second, regarding the Phase I/II study of telaglenastat with IBRANCE, could we expect any data update this year?.

Yes. Arthur, in terms of enrollment for KEAPSAKE, while we don't usually give sort of specific numbers of patients enrolled, I did mention that there is -- there has been some impact from COVID.

I think there's -- it's probably multifactorial, both at the level of the sites who have staff impacted in various ways as well as patients, since this is a front-line study and the patients getting diagnosed in the frontline setting is necessary for patients to be enrolled through the study.

So -- and I think there are ways in which COVID is impacting clinical studies, and we're, like everyone else, experiencing that. But as I mentioned, we still remain on track, we think, for data by the end of the year. The -- and then in terms of the IBRANCE study, that study is enrolling, and we're monitoring the data there.

I have no real update there from an enrollment perspective. I think we talked about the data probably either this year or next with that study, but hard to be more specific than that at this point..

Our next question comes from Matt Phipps with William Blair. Your line is now open..

Coming back on. Keith, I was wondering if we could talk just -- walk through some, I guess, hypothetical next steps after this interim.

So obviously, you'll present the data depending on the level of activity, but is it -- okay, maybe we go take it to the FDA? Or is it, okay, we're just going to continue to let the trial run out? Or is there -- does the trial having some kind of built-in adaptation to expand enrollment to maybe make it pivotal if things are looking good? Just curious what kind of potential next steps are after this interim look in the KEAPSAKE..

So that's a great question, and those are the kinds of things we're thinking about. For example, we can always reach out to FDA with the data if they're compelling. And for example, talk about breakthrough designation, talk about either amending the current study or starting the planning for a subsequent pivotal Phase III.

So those are the kinds of things that, by looking early, we can kind of get a start on what we think the best path is. And again, all of those are really options. And probably an interaction with FDA would be part of that if we were looking to move forward with an accelerated sort of path to approval in some way..

Do you imagine the -- trying to reach out with the FDA would occur before you even present the data given abstract submission time lines?.

So I would say FDA -- interacting with the FDA is independent of any kind of presentation at a meeting. So I wouldn't link those to each other.

And frankly, what we're talking about isn't necessarily even a -- I think what we've talked about in the past is that this may or may not be an actual conference presentation, so -- or may be a prelude to a conference presentation. So that the discussion this year wouldn't necessarily be in the context of a conference..

Thank you. I'm not showing any further questions. And our next question comes from Nick Abbott with Wells Fargo. Your line is now open..

And I apologize I missed nearly all of the prepared remarks. So I want to ask a question on the NCI study of telaglenastat and I know you may not have a lot of insight into that trial, but was updated at the end of January, they're still talking about having data in June.

So do you have any insight into that trial? And is this a way also to help derisk KEAPSAKE in some of these patients who may also have a KEAP1 mutation?.

Yes. So actually, we -- as we talk about of -- hi, Nick, by the way, we don't have any real insight at this point that we can share on the study.

So I think it's an interesting question, whether it's about KEAP mutant patients or just looking at the combination with TKIs targeting driver mutations, I think it's an interesting study and we look forward to learning more about it. But at this point, it's not something that we're able to speak to..

Okay. And then just -- I know there had been a few questions on the IBRANCE combination.

Can you remind us when the colorectal and non-small cell lung cohorts were open for the KRAS mutations? And is that the data you're referring to is possibly being available by the end of this year or beginning of next?.

So that's a good question. You're testing my memory of when the study opened, and I'm not sure I'm going to be able to answer that accurately without looking it up. So I apologize. I can say the pancreatic -- the pancreatic cohort opened more recently. So that was one that we added to the study by amendment.

And so that was, I think, opened late last year. But the timing of the colorectal data -- or the colorectal and lung cohorts opening, I don't know if I can answer that for you as we sit here. I will say, though, that the data that we could present, could be those data and the pancreatic, I think, data from any or all of those cohorts is possible.

But we'll get back to you on the timing of that, the start of the study. I'm sure I should have that ingrained in my head somewhere..

Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Jennifer McNealey for closing remarks..

Thank you, Joelle, and thanks all for joining us today. Have a great evening..

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect..