Good day and thank you for standing by. Welcome to the Calithera Biosciences’ 2Q, 2021 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers’ presentation there will be a question-and-answer session.

[Operator Instructions] I would now like to hand the conference over to your speaker for today, Stephanie Wong. Please go ahead..

Thank you, operator. Good afternoon, everyone. Welcome to our second 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 second quarter 2021 financial and operational results, which can be accessed through our website at calithera.com.

Before we begin, I would like to remind you that today's discussion will include statements about our future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our periodic filings with the SEC.

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.

Please note that this call is being recorded. And with that, I will turn the call over to Susan..

Thanks, Stephanie. Good afternoon, everyone and thank you for joining us today on our second quarter 2021 conference call.

In the second quarter, we continued to execute against our key strategic and operational objectives, which are focused on the advancement of our two lead programs, telaglenastat in non-small cell lung cancer and our oral arginase inhibitor CB-280 for the treatment of cystic fibrosis.

The KEAPSAKE trial evaluating telaglenastat in combination with standard of care chemo immunotherapy for first-line non-small cell lung cancer patients with KEAP1 or NRF2 genetic mutations continues, to enroll and we remain on track to report interim data in the fourth quarter of 2021.

CB-280 continues to enroll patients in our Phase 1b dose escalation study for the treatment of cystic fibrosis. As a reminder, we are conducting this study with support from the Cystic Fibrosis Foundation, including an award of up to $2.4 million for the clinical development of CB-280.

Looking beyond our two core programs, we signed a worldwide license agreement with Antengene for the development and commercialization of CB-708, our internally discovered small molecule CD-73 inhibitor.

In preclinical data presented at AACR and SITC in 2019, we demonstrated that CB-708 has a immune-mediated, single agent activity in syngeneic mouse model and it showed enhanced anti-tumor activity when combined with either anti-PD L1 or with chemotherapy.

In exchange for the exclusive worldwide rights to develop CB-708, we received from Antengene an upfront payment and are eligible to receive additional development, regulatory and sales milestones, as well as tiered royalties on sales of two low double digits.

We view the agreement with Antengene as an important validation of our proprietary drug discovery engine as it demonstrates our ability to discover novel, highly promising therapeutic compounds.

In addition, in June, we joined the Broad Institute’s Cancer Dependency Map or DepMap Consortium, an initiative whose goal is to discover new targets and biomarkers for precision cancer therapeutic. And we look forward to collaborating with them to drive precision medicine forward.

We remain committed to delivering on our mission to bring to market novel therapeutics that address major unmet medical needs.

We believe that the steps we've taken in the first half of 2021 position us well, we expect several important milestones to be achieved in the second half of the year and look forward to providing additional details as they are reached. And with that I will pass the call over to Keith for additional details on our clinical program..

Thank you, Susan. I'll start by providing an update on telaglenastat, our glutaminase inhibitor. As Susan mentioned earlier we are currently enrolling the KEAPSAKE Phase 2 study of telaglenastat in non-small cell lung cancer patients harboring KEAP1/NRF2 mutation.

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 chemo immunotherapy regimen.

Enrollment in KEAPSAKE began in September of 2020 and we remain on track to report interim data from this study in the fourth quarter of this year. The KEAP1/NRF2 mutations are present in an estimated 20% of all nonsquamous, non-small cell lung cases representing approximately 40,000 patients in total.

This is a significant market and an area of high unmet need, which we believe can potentially be addressed by telaglenastat. Our preclinical work with telaglenastat provides strong rationale, supporting the critical role glutaminase plays in the proliferation of KEAP1/NRF2 mutations non-small cell lung cancer tumors.

We believe the telaglenastat has the potential to improve outcomes for these patients and we look forward to further assessing its potential in the KEAPSAKE trial. Turning to CB-280, our novel, oral, arginase inhibitor for the treatment of cystic fibrosis, the Phase 1b dose escalation study continues enrolling on schedule.

As we reported previously, we plan to share data from this study in the second half of 2021.

And I'm pleased to report that interim data from this study was recently accepted for presentation at the North American Cystic Fibrosis Conference taking place at the end of September, and we look forward to sharing these data with investors and members of the medical community at that time.

We are also honored to be joined the Broad’s DepMap Consortium through which we have an opportunity to generate novel data for our discovery programs and make better informed decisions with respect to candidate advancement.

Our interest in biomarker-driven approaches stems from the discovery of KEAP1/NRF2 pathway dependency on glutaminase that drove the rationale for the KEAPSAKE trial.

We plan to utilize this partnership with the Broad to continue to explore biomarkers for telaglenastat as well as identify biomarker defined subpopulations of cancer patients for undisclosed pipeline programs. We look forward to partnering with the Broad to guide the development of our programs in the discovery of new ones.

With that I'll pass it over to Stephanie for an update on our financials..

Thank you, Keith. Detailed financial results for the current quarter were included in today's press release. I will briefly review our results on this call. Calithera remains well-capitalized with cash and investments totaling $92.2 million at June 31, 2021.

Revenue for the quarter was $3 million reflecting revenue recognized from our licensing agreement with Antengene. R&D expenses were $12.8 million in the second quarter of 2021 compared to $15.6 million in the second quarter of 2020.

The decrease was primarily driven by the decreases in telaglenastat and 11.58 programs, partially offset by increased expenses associated with our CB-280 program as well as investment in early stage research. G&A expenses were $4.5 million in the second quarter 2021 compared to $5.1 million in the second quarter of 2020.

The decrease was primarily related to decreases in professional services costs and in rent expense related to our facility lease amendment in March of 2021. Net loss for the second quarter of 2021 was $14.3 million. And with that I will now turn the call over to Susan..

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

Thank you presenters. [Operator Instructions] And we have our first question from Matt Phipps from William Blair. Your line is open..

Hey guys and thanks for taking my question. Just maybe two quick ones from me. I was wondering if, first you might just do you able to comment on the Bayer acquisition of the Vividion this morning obviously their lead program [indiscernible] also and kind of the KEAP1/NRF2 space, but maybe a different approach to that.

And then secondly we talked a little around the abstract of the MD Anderson data with their glutaminase inhibitor. But, so it does have the actual presentation seemed like the greatest benefit they saw were in PD 1 resistant melanoma patients but those patients actually didn't have some of those mutations they were looking for.

So there is any comments on that. And I guess maybe how more these things reflect through the KEAPSAKE program..

Hi, Matt. This is Susan. I can comment on the Vividion acquisition by Bayer.

They are obviously pre-clinically based company with a platform and use their platform to develop both activators and inhibitors in NRF2 and we are clearly interested in inhibitors NRF2 into the clinic at least some population of NRF2 to keep, it isn't completely clear to us exactly with that population would be because they are depending on NRF2 inhibitor to interact with KEAP and be degraded.

But I think it's great, a further validation of how important and interesting the KEAP pathway is and approaches to developing there two inhibitors are certainly, that would be new ground and I think it's great to see Vividion has made some progress.

Obviously we're ahead, we are already in clinical trials, the glutaminase inhibitor, which does affect all of keeping population..

Hey Matt, this is Keith. I mean in terms of the clinical data. I ask you to kind of clarify. But I mean, just generally speaking, the data looked interesting. I think it's an active molecule. It has from a PK and PD perspective.

And I think from a safety profile, there may be some differences there from what we've seen with the telaglenastat program and we'll learn more as those data continue to come in.

I don't know, from an efficacy perspective it there is given the size of that if the sample size, if there is a lot to be gleaned but what was the specific question about the have seen that you were asking..

I was, I mean commenting on those to have the greatest clinical benefit and some PD 1 refractory melanoma patients which you guys also showed some there and your old study of the Nivo combo but they said, those patients actually did have some of the looking for just even enrolled in the study..

Yes, I mean, I do think that's interesting. And we think what we've seen has been is interesting in terms of the PD 1 refractory patients and continues to be an area of interest. So I can't speak to, why they didn't have the mutations that they were looking for.

But the mechanisms of PD 1 resistance, and we've talked about this before, that there is potentially a role for metabolism there and potentially specifically glutamine metabolism. So I do think that's interesting..

Maybe just one plus question, can you give any idea now as we get closer, this in the year readout maybe how many patients you we should expect for the KEAPSAKE interim?.

Yes. So, as we've talked about before that there isn't the specific statistically driven sort of event number patient number that we're targeting for the interim and so I don't have much more in terms of clarity in terms of specific numbers, I don't think we can speak to that at this point. And so I think I'll leave it there..

Okay, thanks Keith..

Yes..

[Operator Instructions] We have our next question from Swayampakula Ramakanth from H.C. Wainwright. Your line is open..

Thank you. Good afternoon Susan and Keith. Couple of quick questions, on the KEAPSAKE trial, the interim data, this is expected in the fourth quarter and would this be and a press release or would this be at a conference and what sort of data should we be expecting at the interim look..

Yes, so in terms of the format or the forum, we're not planning to present at a meeting at that time. So it will be some other format and in terms of the type of data.

We've talked about some before the types of things that we will be looking at are generally response rate in PFS and comparing against the known historical data for this population, which as you know is quite poor median PFS in the three to five month range. And so that's really what we'll be focused on..

Okay, thanks. And then just trying to understand the Cystic Fibrosis franchise with the interim data again expected soon at the end of September.

So is there, what is the expectation on the timing for completion of this trial and what would be the next steps in this for this molecule in your hands or do you think that just to move to the next level you need to have a partnership?.

Thanks. So the CF program, the study is an ongoing studies that we'll be presenting data from the ongoing dose escalation. We expect that study to be completed this year.

And in terms of next steps, what we have discussed previously that this is what we would follow would be a dose-ranging study across a few different dose levels to be determined based on the data that come out of the dose escalation but with the goal of having [indiscernible] as a primary endpoint and to select the dose for further development.

And I think it's. I wouldn't say that a partnership is required at all to move forward to that next phase of development..

Okay. And then, last question from me is just to think about in a long-term pipeline with the CD7 or 8 under which just underwent license agreement. Susan, what – how should we think about like pipeline growth from here onwards.

Is there something in the preclinical development and should we be expecting another molecule come to the forefront maybe in the next say 12 to 18 months?.

That's good question and we haven't talk lately about our preclinical pipeline, but I will say that our research group remains quite active. I will point to the fact that we just joined the Broad Institute.

I think that reflects our increasing interest in biomarker driven approaches such as we're taking in the KEAPSAKE trial and that will be our area of interest most likely going forward.

We like the idea of being able to find genetic mutations in specific populations where a particular drug to be targeted at that of course is the case for glutaminase in the nurse keep pathway mutants in lung cancer.

So we aren't in a position to say anything now, but our research group is active and I would fully expect preclinical programs in the future to come out in oncology and in the very general area of biomarker driven approaches to target validation and making inhibitors of targets..

Perfect, thank you. Thank you for taking all my questions..

Welcome..

Thanks, RK..

And there are no further questions at this time, I will hand the call over back to the presenters..

Thank you, operator and thanks all for joining us today and have a good evening..

Ladies and gentlemen, this concludes today’s presentation. Thank you for participating. You may now disconnect..