Good day and thank you for standing by. Welcome to the Calithera Biosciences First Quarter 2021 Earnings 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 over to your first speaker today, Stephanie Wong. Please go ahead..

Thanks, Jeff. Good afternoon, everyone. Welcome to our first quarter 2021 Conference Call. Joining me today are Susan Molineaux, Founder, President and CEO; and Keith Orford Chief, Medical Officer.

Earlier this afternoon, we issued a press release, which included an overview of our first quarter 2021 financial and operational results, which can be accessed through our website at calithera.com..

Thanks, Stephanie, and good afternoon, everyone. Thank you for joining us today on our first quarter 2021 conference call. On behalf of the entire team, I'd like to say, we hope that you and your friends and families remain healthy.

As the world continues to push forward to contain COVID-19, we are grateful to the scientists, companies, and frontline workers that have worked to achieve monumental milestones in developing and deploying vaccine.

Their dedication has allowed many of us to return to some sense of normalcy and allowed people to return to their medical centers for treatment of serious illnesses like cancer and cystic fibrosis where Calithera is working to develop novel drug therapies that will make a difference to patients.

In the first quarter, we have been busy advancing our two key clinical programs, which both have data readouts expected later this year. First, the randomized KEAPSAKE trial has continued to enroll non-small cell lung cancer patients.

KEAPSAKE is evaluating telaglenastat in combination with standard of care chemoimmunotherapy for first-line non-small cell lung cancer patients with KEAP1 or NRF2 genetic mutation. We anticipate releasing interim data for this trial in the fourth quarter of 2021.

We also continue to evaluate telaglenastat in additional indications and combinations and in investigator sponsored trial. Secondly, our oral arginase inhibitor, CB-280, for the treatment of cystic fibrosis is continuing to enroll patients in a Phase Ib dose escalation trial.

As you know, our interest in arginase stems from the Incyte 1158 molecule that is partnered with, and being developed by Incyte for the treatment of cancer. Arginase also plays a critical role in cystic fibrosis airway disease and arginase inhibition could be a potential treatment.

We identified CB-280, a first-in-class oral arginase inhibitor wholly owned by Calithera for evaluation in this patient population..

Thank you, Susan. And I'll start by providing an update around telaglenastat, our glutaminase inhibitor. We are evaluating telaglenastat in a non-small cell lung cancer patient population with a targeted biomarker-driven approach in the KEAPSAKE trial.

Over the last couple of years, retrospective analysis have shown that non-small cell lung cancer patients with KEAP1 or NRF2 mutations have poor prognostic outcomes in wild-type patients and that these patients may not respond well to standard of care chemoimmunotherapy.

KEAP1/NRF2 driver mutations protect tumors from oxidative stress and promote tumor growth and survival. Preclinical models have shown that activation of a 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.

In the KEAPSAKE trial, patients are 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 this standard-of-care chemoimmunotherapy regimen.

We plan on enrolling 120 patients and begin enrolling this study in September 2020. This is an area of unmet clinical need as an estimated 20% of non-squamous, non-small cell lung cancer patients have tumors harboring KEAP1 or NRF2 mutations.

Based on preclinical studies that provide a strong mechanistic rationale the central role of glutaminase and driving proliferation in non-small cell lung cancer tumors harboring KEAP1/NRF2 mutation, we believe that the KEAPSAKE trial has the potential to improve outcomes for these patients and we look forward to being able to share interim data in the fourth quarter of this year..

Stephanie Wong:.

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

Okay, thank you. I will first speaker - our first question comes from the line of Mohit Bansal of Citi. Sir, your line is open..

Hey, guys. This is James on for Mohit. Thanks for taking my question.

Just two quick ones, for KEAPSAKE, you sort of given us expectations for the control arm, but can you sort of consider - can you share like what you would consider to be good ORR in PFS data for the patients on telaglenastat? And then related to KEAPSAKE, for the 4Q readout, are you planning to release data in a press release or is that something that you could reserve for like a larger medical conference? Thanks..

Hi, James.

So in terms of the data, yeah, as we've talked about before kind of what we would expect the ballpark to be for the control arm, maybe a median PFS in the three to five months range, in terms of what good data looks like, I mean, I think the key point is that we're looking for this to be a substantial improvement over the control arm and over how poorly these patients do today.

So we're really not looking for really small incremental improvements. So I hesitate to provide a specific number or a specific PFS. But the goal here is for it to be a clear improvement and we're not looking for something subtle. Presumably, when all is said and done, that's something you need a statistician to determine, to put it that way.

And then in terms of how it will be done, I think we're not necessarily going to wait for a medical conference. We'll see what - based on the timing, how that works out..

Got it. Appreciate it, guys. Thank you..

Yeah..

Thank you. Next question from the line of Matt Phipps of William Blair. Your line is open..

Hi, guys, this is Rob Andrew here on for Matt Phipps. Just a couple if I may. So first one, it was an interesting presentation a couple of weeks ago here at AACR.

That was kind of highlighting ferroptosis as a key pathway through which T-cell mediated killing of tumor cells occurs and it seems in the literature that some evidence that NRF2 could be involved in this pathway since it's kind of cancer regulated by glutathione.

And then similarly exports of intercellular glutamate has been linked to suppression of the pathway as well.

So we were just kind of wondering whether you've seen any evidence preclinically that telaglenastat can influence ferroptosis pathway and whether there's potential to think here that that could be an additional mechanism of action for telaglenastat? And then the second question is just kind of similar to a previous question on KEAPSAKE but on CB-280.

Just on what expectations are there in terms of the data is in conjunction with the medical meeting or expecting top line results press released? Thanks..

Yeah. Hi, Rob. Yeah, so I think the story around ferroptosis is an interesting one and certainly a developing one. I think not an area of focus, particularly earlier on in the development of the program when much of these data were generated. I think, I mean, that might be a good conversation for our Head of Research, Frank Parlati, to discuss further.

But in terms of our clinical studies, again, it's not something we've looked at there in that context.

So it's something we're very interested in and we certainly think given the relationship between both - as you say, both glutamate and NRF2 pathway with ferroptosis and that this is potentially a very interesting mechanism, but not - wasn't central I guess to the early data that we had put together preclinically at the time that we did that.

It's really emerged over the last year or two. So I guess I would say to be determined, but certainly very interesting. And then in terms of CB-280, again, we'll let you know. I think our approach generally is to inform on if we are going to be reporting at a conference to do that once we have been accepted to that conference.

So we will let you know, I guess, as that approaches..

Great. Thanks for taking the questions..

Yeah..

Thank you. Next question from the line of Nick Abbott of Wells Fargo Securities. Your line is open..

Hi guys, it's Joe on for Nick. Congrats on the progress and appreciate you taking the question. Just a quick one from us, apologies if I missed it, but have you provided an update on the NCI sponsored Tagrisso combo study, the on-perm trials; the primary completion date is second quarter of 2021.

So should we be expecting data prior to the KEAPSAKE read-out or maybe how should we think about that?.

Yeah. Thanks Joe. For all of our, sort of external studies that we don't sponsor including CPAP studies, it's hard for us to comment much on timing.

So no, we haven't released any data and it really wouldn't be our data to release, but those data have not been discussed publicly and to be honest, we don't have - it's not like we're in constant communication and have total visibility of that. So that will be on NCI's timeline and I can't really speak to that right now.

But as far as we know, these are moving along well and there are no issues, but we just don't have specific data to talk about today..

Yeah. No, understood, Keith. Appreciate it. Thank you for the comment there..

Yeah..

Okay, thank you. There are no further questions at this time. Please continue..

Okay, thank you. Thanks all for joining today and have a good evening..

Great, thank you. And that concludes today's conference call. Thank you for participating. You may now all disconnect..