Good afternoon, ladies and gentlemen, and welcome to the Calithera Biosciences First Quarter 2020 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 today, Ms.

Jennifer McNealey. You may begin..

Thank you, Christie. Good afternoon, everyone. Welcome to our first quarter 2020 conference call. Joining me today are Susan Molineaux, our Founder, President and CEO; Keith Orford, Chief Medical Officer; and Stephanie Wong, Senior Vice President of Finance.We have issued our press release and it 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 the 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 in the risk factors discussed in the Risk Factors section of our quarterly report on Form 10-Q filed 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, this call is being recorded.And with that, I'll turn the call over to Susan..

Thanks, Jennifer. Good afternoon, everyone. And thank you for joining us today on our first quarter 2020 conference call.

On behalf of the entire team, I'd like to say, we hope that you and your families remain healthy, while the world addresses the challenges of the COVID-19 pandemic.Today, on this call, we are all working from our homes as has been our practice now for a number of weeks in compliance with the CBC, California State guidelines and San Mateo County guidelines.

We are diligently coordinating our activities to maintain ongoing business operations.

We look forward to going back to our on-site operations as soon as we can do so safely.At Calithera, we are building an integrated biotechnology company that develops novel small molecule oncometabolism 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 the first company to take a selective glutaminase inhibitor into the clinic and the first to demonstrate clinical activity in cancer patients including proof-of-concept for the activity of telaglenastat in renal cell carcinoma in our randomized ENTRATA trial.We have fully enrolled the telaglenastat CANTATA trial, a study with registration potential in renal cell carcinoma patients.

This moves us a step closer to becoming a commercial biotechnology company. The CANTATA trial was fully enrolled in October 2019.

And we advised at that time that we plan to report top-line efficacy and safety data from the trial in the second half of 2020.In light of delays associated with COVID-19, we updated our guidance in April to expect top-line data in the fourth quarter of 2020.

Along with affirming that the readout is expected by the end of 2020, the updated guidance allows for additional time for activities that require visits to clinical sites, including data monitoring.In this quarter, we also made continued progress towards initiating a randomized trial in first line non-small cell lung cancer patients harboring genetic mutations in NRF or KEAP.

A mutation of the KEAP1/NRF2 pathway is present in approximately 20% of tumors in non-small cell lung cancer patients and is associated with core survival and resistance with standard-of-care therapy.Activation of this pathway leads to reliance upon glutaminase activity and sensitize itself to glutaminase inhibition of telaglenastat.

Given the challenges associated with opening new clinical study during the current stage of the COVID-19 pandemic, we expect to begin enrollment in the third quarter of 2020.A trial and progress abstract describing the study design has been accepted for presentation at the American Society of Clinical Oncology of 2020 Virtual Meeting.

We plan to present interim data from this trial in 2021.Our arginase inhibitor, INCB001158 or 1158 is the first arginase inhibitor to enter the clinic. Arginase is an immunosuppressive enzyme expressed by immune cells in the tumor microenvironment.

At the ESMO Meeting last fall, the first efficacy data for this compound were presented, demonstrating activity and providing proof-of-concept for arginase inhibition for the treatment of cancer.We are pleased with the progress of this program as we continue in collaboration with our partner, Incyte to continue clinical trials and seek to develop a first-in-class product for patients with multiple types of solid tumors.Calithera has filed a complaint against Incyte in the Superior Court of California, San Francisco County, as certain claims for breach of contract arising at Incyte's failure to pay two milestone payments the company believes are due under the agreement.

We do not plan to comment further on this matter at this time.The timeline for the clinical trial from the program remain as before and have not been impacted by the filing of the complaint.

Arginase inhibitors also have potential in the treatment of cystic fibrosis.Accordingly, we have selected CB-280, a unique oral arginase inhibitor for the treatment of cystic fibrosis patients. It is a novel oral arginase inhibitor that is solely owned by Calithera.

We have completed a Phase I single ascending dose trial to evaluate the safety, tolerability and pharmacokinetics profile of oral CB-280 in healthy volunteers.Our Phase I b clinical study in people with cystic fibrosis is poised to begin.

Site openings are in progress and we expect enrollment of the first patient in the third quarter of 2020, pulling further development in the COVID-19 situation.Beyond our three clinical-stage programs, we have a broad pipeline and a productive R&D team.

We remain focused on producing novel drug candidates with the potential to be highly differentiated new therapies in areas of unmet need.With that, I will pass the call over to Keith for additional details on our clinical progress..

Thank you, Susan. Let's begin with a more detailed update on telaglenastat, our glutaminase inhibitor and our most advanced product candidate.

We are currently focused on forging a clinical and potentially commercial path for telaglenastat in renal cell carcinoma.In October 2019, we announced completion of enrollment of CANTATA, a global, randomized, double-blind trial of telaglenastat in combination with cabozantinib in second and third-line RCC patients.CANTATA enrolled 444 patients ahead of schedule, demonstrating the significant unmet need for advanced RCC patients in the second and third-line settings.

CANTATA is designed to evaluate the efficacy and safety of telaglenastat in combination with cabozantinib versus placebo plus cabozantinib in clear cell RCC patients who have previously received one or two prior lines of therapy, including at least one prior anti-angiogenic agent or the ipilimumab nivolumab combination.Patients were randomized in a 1-to-1 ratio to either telaglenastat plus cabozantinib or placebo plus cabozantinib.

Patients were stratified by IMDC risk category and prior treatment with an anti-PD-1, a PD-L1 therapy. The primary endpoint is progression-free survival by independent review.

Overall survival will be assessed as a key secondary endpoint.We have made accommodations to facilitate study conduct during the pandemic, including allowing patients to have scans performed at local clinical centers to facilitate compliance with the study schedule of assessments and to receive a larger allocation of study drug in order to reduce the number of visits required to clinical sites, if necessary.The trial has the potential to serve as a registrational trial and we expect to report top-line results of CANTATA in the fourth quarter of 2020.

We also believe telaglenastat has the potential to be developed in patients with NRF2/KEAP1 mutations.Multiple in vivo preclinical models have demonstrated that activation of this pathway through loss of function KEAP1 mutations or a gain of function NRF2 mutation accelerates tumor formation and spread.

In addition to making tumor models more aggressive, the activation of the NRF2/KEAP1 pathway also makes them sensitive to the inhibition of glutaminase activity by telaglenastat.Recently presented clinical data have demonstrated that activation of the NRF2/KEAP1 pathway results in very poor outcomes in non-small cell lung cancer patients receiving frontline standard-of-care chemotherapy or chemoimmunotherapy.Mutations in the KEAP1/NRF2 pathway are present in approximately 20% of non-squamous non-small cell lung cancers.

Based on the unmet need in this population, we have designed a randomized trial in lung cancer patients, which we expect to begin in the third quarter of 2020.The study will evaluate telaglenastat in combination with standard-of-care therapy, chemo plus pembro, in approximately 120 first-line metastatic non-squamous, non-small cell lung cancer patients with tumors that harbor mutations in either KEAP1 or NRF2.

The study will include an initial safety run-in period and the co-primary endpoints are safety and investigator-assessed progression-free survival.A trial and progress abstract describing the study design has been accepted for presentation at the American Society of Clinical Oncology 2020 Virtual Meeting.

An interim analysis is planned in 2021.In addition, an NCI sponsored trial, evaluating single-agent telaglenastat in patients with solid tumors that have NRF2 or KEAP1 mutations is currently ongoing.We are also conducting two exploratory Phase Ib/II trials in collaboration with Pfizer, combining telaglenastat with TALZENNA and with IBRANCE.

Dose escalation has been completed in both of these trials. Dose expansion cohorts have been temporarily paused due to the COVID-19 situation, but we now expect enrollment to resume in the second quarter of 2020.Next, the arginase inhibitor programs.

INCB001158 also known as 1158, is an investigational first-in-class immunooncology metabolic checkpoint inhibitor targeting arginase, an immunosuppressive enzyme secreted by myeloid-derived suppressor cells or MDSCs to block T-cell activation in tumors.

1158 is being developed with Incyte in a co-development, co-commercialization collaboration.1158 is being evaluated as monotherapy, as well as in combination with pembrolizumab across eight cohorts of patients with different types of metastatic or locally advanced cancers not amenable to local therapy.

The first data from this study were presented at ESMO in September 2019.The second ongoing clinical trial is evaluating 1158 in combination with three different chemotherapy regimens. FOLFOX, gemcitabine/cisplatin or paclitaxel in patients with ovarian, endometrial, colorectal, gastroesophageal and biliary tract cancers.

An additional trial in multiple myeloma patients, treating patients with 1158, plus daratumumab or daratumumab alone is also ongoing.We are pleased with the progress of this program and we look forward to additional data updates from the 1158 program in the future.We are also developing an arginase inhibitor outside of oncology.

CB-280 is a novel arginase inhibitor in development for the treatment of cystic fibrosis.

Under our collaboration agreement with Incyte, we’ve retained worldwide rights to develop arginase inhibitors in specific non-oncology rare disease indications, including cystic fibrosis.Arginase has been postulated to play a critical role in the pathophysiology of cystic fibrosis, as well as several other non-oncology diseases.

CF patients have neutrophil infiltrates in their lungs and these neutrophils secrete high levels of arginase. High arginase activity depletes arginine, which in turn depletes nitric oxide.Nitric oxide or NO has potent antimicrobial activity and exogenous NO has been shown to improve lung function when administered to CF patients.

We hypothesized that inhibition of arginase with CB-280 can restore normal arginine and NO levels and improve lung function in CF patients, a concept that is supported by previous proof-of-concept clinical trials.The Phase I clinical trial to evaluate the safety, tolerability and pharmacokinetic profile of oral CB-280 in healthy volunteers has been successfully completed.

A Phase Ib clinical study in CF patients, which is expected to start enrollment in the third quarter of 2020 will test multiple doses of CB-280, compared to placebo in approximately 30 adult CF patients to determine a safe dose range for CB-280.Patients with any CFTR mutational status will be eligible for the study.

Patients will receive CB-280 or placebo for 14 days.

In addition to safety and tolerability, other endpoints will include pulmonary NO production, lung function and sputum microbes.In a planned Phase II dose-finding portion of this study, additional cohorts of patients will receive different doses of CB-280 or placebo, for 28 days in order to select the optimal dose of CB-280.For the entire study, patients will continue their existing therapies for CF, including CFTR modulators.

We plan to present data from the Phase Ib portion of this trial in 2021.With that, I'll pass it over to Stephanie for an update on our financials..

Thank you, Keith, and good afternoon, everyone. Detailed financial results for the first quarter 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 $138.1 million at March 31, 2020.

In April, we completed a public offering of 5,750,000 shares of common stock for net proceeds of approximately $33.5 million.

We believe our cash position enables us to drive our clinical programs to meaningful value inflection points.R&D expenses were $20.1 million for the quarter ended March 31, 2020, compared to $20.2 million for the same period prior year.

The decrease was primarily due to a $1.2 million decrease in the 1158 program and a decrease of $0.8 million in early-stage research, partially offset by an increase of $1.4 million in the telaglenastat program and an increase of $0.5 million in the CB-280 program.G&A expenses were $4.9 million for the quarter ended March 31, 2020, compared with $4.2 million for the same period prior year.

The increase was primarily related to $0.5 million in higher professional services costs and $0.2 million in higher facilities costs.Interest and other income net, was $0.6 million for the three months ended March 31, 2020, compared to $0.7 million for the same period prior year.

Net loss for the three months ended March 31, 2020 was $24.4 million or $0.38 per share.And with that, I will now return the call back over to Susan..

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

[Operator Instructions] We have our first question comes from Mohit Bansal..

Hi guys. This is James on for Mohit.

Just had a question on, has COVID given you affirmation to focus your pipeline on oral administration? Also, are you seeing any changes to your plans for manufacturing or marketing due to the pandemic?.

Keith, do you want to answer that oral question, if at all?.

Hey, James. Yes, actually, I am sorry, I didn't quite capture the very beginning of your question about the oral.

What was the question?.

I was just asking if COVID has given you affirmation to focus more of your pipeline on oral administration products..

Well, I would say that the impact, having an orally administered – having orally administered drugs in the context of COVID has been probably less disruptive than it would be for patients if they were having to go in for infusions on a regular basis.

Whether that's changed our longer-term sort of strategy around that, I think that's been our – focus has been orally administered drugs all along.So, it certainly provides support for that approach and it’s helpful in this context. I am not sure in the longer-term it has a longer-term impact on our strategy. But in general, that's our focus anyway..

And James, you had a question about manufacturing. Could you repeat it, please? Sorry..

Yes.

Just wondering if COVID has changed how you are thinking about with partnering for manufacturing or some of your strategies for marketing? Has COVID thrown any changes to how you are thinking about those things?.

Not at this time. We have no issues with our suppliers for API or drug product for telaglenastat or for the arginase inhibitor. So we are feeling good right now.

We, of course, always have strategy to increase our backup manufacturers, both study materials, as well as API as time goes on.So, as we get closer to commercialization, we do plan to diversify where we manufacture our drugs. But right now, we have not yet experienced any major delays..

Got it. If I could ask one more, given that certain states seem to be loosening social distancing protocols sort of at relatively different degree.

Is there a chance some of your studies could see enrollment gets started sooner than others?.

Well, so that's a good question. I mean, I don't know on a – from a state-by-state perspective, changes that are happening in different localities. And just it’s the difference of impact and maybe the different approaches the local areas are taking.

I would say, sites are taking different approaches or are loosening up at different times again, based on the sort of the local environment.So, you could imagine maybe sites in New York are having a different approach than sites in an area that just haven't seen much of the disease at all.So having said that, as we just said, we are going to be able to – we think, open up our ongoing study, the two Pfizer combinations where we had paused enrollment, because that's an already open study, that's – we are hearing from sites that we should be able to start enrolling in this quarter.And that's a different proposition than opening a new study that requires IRB review and so forth.

So, we are looking to open those studies sooner. And as we mentioned, the two new studies that we expect – that we are opening, the KEAPSAKE study and our Phase Ib study in CF patients, both of those we plan to open in the third quarter.Whether it's – so - and so I think those remain on track.

So that, we are hearing signs, I guess, what I would call, signs of life from our sites. They are starting to now think about opening and enrolling. And so, that's allowed us to really start the planning processes for the next steps in these studies..

Thanks guys. Appreciate it..

Our next question comes from the line of Jonathan Chang. Jonathan, you may begin your question..

Hi team. This is John Barrett on for Jonathan. Just two questions from me. Back in – back at ESMO when you presented the ENTRATA data, I recall that the overall survival data was not yet mature.

I was just wondering if you had an update on whether or not that data is mature? And if we could – and when or if we could see that data?.

Yes. So, we don't have an analysis of the mature data at this point. As of the last analysis, it was not yet mature. But we would be expecting it to mature and when it does, we will be presenting it, either in the context of a manuscript or a presentation. So, it will be coming, but at this point, not ready to be presented, not mature..

Got you. And one question on the KEAP1 strategy.

Of course, you’ve presented some data and there's been a lot of publications on the solid rationale for testing a glutaminase inhibitor in this patient population.But just as an exercise and risk management and based on your data conversations with KOLs, can you discuss any areas of concerns or thoughts on why glutaminase might not work in this population?.

What I would say is that, our investigators, including the preclinical investigators who have kind of done the work and our clinical investigators are very enthusiastic about studying glutaminase inhibition. I mean, we don't go into any study with a 100% certainty of activity.

That's why we run the studies.But this one, I would say, there's particular enthusiasm around based on both the strength of the preclinical data, the really strong - just mechanistic rationale in addition to the actual data, but it just makes good sense based on understanding the biology.

And then finally, the really high unmet need in this population has become very clear broadly throughout the lung cancer community.So, the main focus of our discussions has been just around the enthusiasm for the data and the huge unmet need. And so they are looking forward to getting this study started..

Great. Thank you so much..

Next question comes from the line of Jim Birchenough..

Hi guys. Congrats on all the progress. A couple of questions. I guess, just sticking with the KEAPSAKE study for telaglenastat.

Could you just talk about current standard-of-care for those patients with the mutation? Do they have a lower mutational burden and are less amenable to PD-1 inhibition? Or maybe you could just talk about the standard-of-care and what you are looking to add to or improve upon?.

Yes, sure. So this population doesn't have a unique standard-of-cares for it. So these patients get what is effectively the current standard-of-care for most patients who will get chemo plus pembro in the front-line setting. Although, it's also approved – pembro alone is approved in the PD-L1 positive population.

So either of them are approved therapies.And I would say that the chemo plus pembro is what's being used generally. In terms of their – how they behave. They certainly do poorly and that's been published multiple times now that this population does not do well, that it's a very poor prognostic factor.

The exact mechanistic cause of that is not totally clear. KEAP1 is not necessarily associated with being PD-L1 low.It's got a fairly standard distribution of PD-L1 expression. And so that doesn't seem to be the driving force.

I think in terms of TMB, it's not particularly out of the norm there either.So, there is no clear rationale from that perspective that might provide a clue.

I think the preclinical data suggests that these patients are just much better at managing the reactive oxygen stress that these cancer cells generally have to manage and, therefore, are more aggressive.And – so there is nice preclinical data to support that mechanistic reason for them being poor prognostic.

And that's consistent with what we hear from investigators. They often will tell us when these patients walk in the door, you have – you kind of know or you have a good sense of who the KEAP1 mutant patients are going to be, because their disease is more aggressive.So there is clearly a different biology there.

It's not just about response to therapy, but it's actually just about more aggressive disease. It's an overall bad prognostic factor..

And so, I recognize we'll get detail on the trial design at the ASCO Virtual Meeting.

But is the idea that you'd look to study – do the randomized study in patients progressing on a PD-1 based therapy?.

No. These are frontline patients. So we're looking at first-line patients who have not received any prior therapy for metastatic disease. So this will be their first exposure to pembro plus chemo, again, standard frontline therapy, we're adding on top of it. The study is going to be standard pembro, chemo, plus or minus telaglenastat..

Got it. Okay. And then, maybe just one on CB-280.

Just on the 28-day timeframe to try and assess benefit of the drug, is that enough time to see a functional benefit on something like forced vital capacity or FEV1? Or would you be looking more at biomarkers to assess optimal dose?.

No, we would expect to be able to see FEV1 improvements. In fact, that will be the primary endpoint of the 28-day Phase II portion of the study will be FEV1.

We have – I mean, certainly, from the CFTR modulator perspective, improvements in FEV1 happened relatively quickly.And even in patients who receive, there have been proof-of-concept studies done in patients, treating them with arginine, whether it's IV or inhaled and improvements have been seen there as well in FEV1 and they've happened within two weeks.

And so, our expectation is that certainly in four weeks and even within two weeks, we may be able to start seeing FEV1 improvements..

Great. Thanks for taking the questions.

Yes, thanks, Jim..

Next question comes from the line of Arthur He..

Hey guys. Thanks for taking my question. This is Arthur for RK. So I have a question regarding on the KEAPSAKE trial.

For the interim readout, what kind of data set we could expect it for that?.

Yes. So, we are looking – so we'd be focused on PFS as the endpoint and as we mentioned, the study is about 120 patients.

So we will be looking for at a subset of that, probably half or a little less than half of the patients having relatively mature data.The data for these patients will – because of the short PFS expected for the MD Anderson dataset, that PFS was around 2.8 months, the median PFS for this population. We will expect it to be a little longer than that.

But we would expect that medium PFS to be relatively short, unfortunately for these patients. So we expect to be able to get a relatively good look at PFS from that first 50 to 60 patients..

Thank you very much for that color.

And maybe just to follow-up on that part, is there any subgroup stratify according to the KEAP1/NRF2 mutation or other criteria for the patients?.

Yes. So, there will be stratification factors in the study. We are focusing mostly on the STK11 gene or also called LKB1. So, this is another highly prognostic mutation similar to KEAP1 in terms of its prognostic significance.And so, in order to – so that's an important factor that we'd like to have balanced between the arms.

So it'll be stratified by mutation to STK11, as well as to the M1a versus M1bc status. So, essentially, their staging criteria will be – which is again, prognostic and so, we want to get these important prognostic variables to be well-balanced between the arms..

I see. Thanks for that color..

Yes..

Our last question comes from the line of Matt Phipps..

All right. Thanks for getting me in there. So, at AACR, Ipsen had a nice presentation looking at this pathway, the KEAP1/NRF2 pathway.

And they showed a combo pre-clinical trial with the mTOR inhibitors and Takeda is going to have some data at ASCO looking at their mTOR inhibitor in this patient population.Obviously, focus for you guys on getting KEYTRUDA chemo combo start-off, but are you seriously considering some other combos in these patients now? Or would you wait and see some of the interim data before kind of branching into additional trials in this setting?.

So the – the combination with the TORC1/2 inhibitors are very interesting to us. There are very nice preclinical data. We've been working with a group – academic group that has that. And in fact, there is a study that's planned, and actually in the process of opening.

That's combining telaglenastat with TORC1/2 inhibitors.So, that's something we are very interested in. Mechanistically, we think the rationale is very strong. We generally agree with the data that have been presented by Ipsen.

I think they've done a nice – really nice job of sort of validating the work that we've done and the biology that we've been talking about. So, we are – we think that was a great presentation at AACR. And we certainly support and are interested in this combination with TORC1/2 inhibitors..

Thanks, Keith. And then, for 1158 at ESMO last year, you guys kind of disclosed that the Simon Stage 2 had been reached for both colorectal, which you showed some data for, but also head and neck when the others were all still in stage one.

I am guessing, you can't say at this point, but any other indications moved on to Stage 2? And, do you think we'd get an update in the next six months or the more next 12 months?.

Yes. We are not at liberty to talk about the other cohorts. But you are right, the head and neck one had move from Stage 1 to Stage 2. And we will – we can't really guide right now on when we'll be able to present that.As you know, we will be at a discussion between ourselves and Incyte and that kind of a joint decision around the right timing.

We do like to wait for these cohorts to be mature. And so, we have a good feel for things like the response rate and the durability of those responses and even the PFS in these groups.So, at this point, no guidance on that. But you are right, head and neck has reached Stage 2 and the others are ongoing..

Okay. And then one last question. So, CheckMate 9ER, obviously, just read out positive and assumptions are Cabometyx will be able to gain more traction in the frontline setting. Obviously, we have to see the results of the CANTATA trial.

But, do you envision that a physician would be hesitant to provide a cabo containing regimen for a patient who maybe relapsed on cabo-nivo in the frontline setting?.

Yes. I mean, we've – as we've talked about this in the past in the sense that we were fully expecting this study to be positive. There was no reason to think that they wouldn't have a positive study here.

Obviously, that frontline space is fairly competitive and fractionated amongst a number of regimens that are including IO therapies.Several of which are – at least two of which I think are pretty well entrenched at this point. I would agree, I think it's an open question.

But we would agree that patients coming off of cabo in the frontline would be less likely to come on to a cabo containing regimen in the second-line.Having said that, again, we think that the majority - probably the large majority of patients will come off of frontline, not having seen cabo.

And so, we still seek second-line as being a great place for cabo to be used and for a cabo combination to be approved in.Having said that, we have the potential to look at other combinations, other TKIs or even look at frontline down the road. So there is other places we could go with telaglenastat.

But, we are pretty confident that the second-line space remains a very good place for cabo combination..

Yes. Thanks, Keith. Appreciate it..

Yes. Thanks, Matt..

There are no more questions on the phone line. I will turn the call over to Ms. Jennifer McNealey..

Thank you, Christie, and thank you all for joining us. And have a great evening..

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