Thank you for standing by. And welcome to the Calithera Biosciences Q3 2020 Earnings Call. At this time, all participants are in a listen-only mode. After the speakers’ remarks, there will be a question-and-answer session. [Operator Instructions] I will now turn the call over to your speaker for today, Ms. Jennifer McNealey. Please begin..

Thank you, Jenny. Good afternoon, everyone. Welcome to our third 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 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 third quarter 2020 conference call. On behalf of the entire team, I'd like to say we hope that you and your friends and family remain healthy. While the world addresses the new challenges including the COVID-19 pandemic.

We've adapted as a company to the new normal work environment, and we are prepared to maintain working from home for most of our employees into the coming month. At the same time, we've successfully reopened our labs and have been able to maintain a safe and productive environment for those workers who have returned to the office.

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 while balancing it with all of the personal challenges that COVID-19 brings. We are both appreciative and proud of our entire team. Today 2020 has been a significant year for Calithera.

As we make remarkable progress to advance our clinical development efforts across our pipeline, and work toward reporting our first pivotal trial results with our lead candidate glutaminase inhibitor, telaglenastat, while continuing to strengthen our cash position.

At Calithera, we are building an integrated biotechnology company that develops novel small molecule onco metabolism drug, 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.

CANTATA, a trial with registration potential in renal cell carcinoma patients, is fully enrolled with top line data expected in late fourth quarter 2020 or early first quarter 2021. This moves us a step closer to becoming a commercial biotechnology company, and we are focused on laying out the infrastructure and plans needed for a successful future.

We are developing telaglenastat broadly and have initiated the randomized KEAPSAKE trial in first line non-small cell lung cancer patients, hovering genetic mutations in KEAP1/NRF2. Study sites are now open for enrollment in the KEAPSAKE trial, and we enrolled our first patient in September.

We also continue to evaluate telaglenastat in multiple indications and this week announced an expansion of our telaglenastat IBRANCE combination trial. We are pleased to be working with Pfizer as part of this productive clinical collaboration.

Our partnered arginase inhibitor program is ongoing with Incyte, where we have a number of clinical trials evaluating 1158 for the treatment of cancer.

While we remain committed to and confident in the 1158 development program, we have decided to opt out of our co-development obligations at this time effective September 30, as permitted under the terms of the inside agreement, in order to focus our resources on our own internal development program.

Arginase inhibitors also have potential in the treatment of cystic fibrosis. Accordingly, we selected CB-280, a unique oral arginase inhibitor, for the treatment of this patient population. Earlier this week, we announced that we were awarded up to $2.4 million from the Cystic Fibrosis Foundation to support clinical development of CB-280.

We are grateful to the Cystic Fibrosis Foundation for their support, and we are very pleased to be working with them. We have a broad pipeline and a productive R&D team and we remain focused on producing novel drug candidates with the potential to be highly differentiated new therapies in areas of unmet need.

And with that, I will pass the call over to Keith for additional details on our clinical programs..

telaglenastat when added to everolimus doubled the median PFS in heavily pretreated patients with advanced RCC to 3.8 months as compared to 1.9 months for everolimus alone and reduced the risk of disease progression or death by 36%. The hazard ratio was 0.64 with a one-sided p-value of 0.079.

Although the study was not powered for survival, it was evaluated as a secondary endpoint and is now mature enough to be reported.

Based on the data cutoff of September 30, 2020, the median overall survival is 14.4 months versus 9.7 months in the telaglenastat and control arms, respectively, with a hazard ratio of 0.80 and a one-sided p-value of 0.24.

To put this data in context, this was a small, signal-seeking Phase 2 study that was meant to look for a trend toward improved PFS and was not powered for overall survival. Given the small size of the trial, we recognize the limitations of the data but are pleased with the trends observed in this advanced patient population.

We also believe telaglenastat has the potential to be developed in patients with KEAP1/NRF2 mutations. Mutations in KEAP1/NRF2 pathway, which occurred in estimated 20% of non-small cell lung cancer patients, are associated with aggressive tumor growth.

Recently presented clinical data 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 chemo immunotherapy.

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 Keepsake, enrolled the first patient in September 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/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 chemo immunotherapy regimen. We plan to share interim data from this study in 2021.

We are also conducting an exploratory Phase 1b/2 trial in collaboration with Pfizer, combining telaglenastat with IBRANCE. We are pleased to announce the expansion of that collaboration to evaluate the combination in pancreatic cancer patients.

The initial combination trial evaluated the combination in patients with solid tumors, including expansion cohorts in KRAS-mutated colorectal cancer and KRAS-mutated non-small cell lung cancer.

Encouraging efficacy and safety of the combination was observed in PDAC patients, pancreatic ductal adenocarcinoma patients, treated in the dose escalation phase of the trial, leading to the expansion cohort.

The new cohort of the Phase 1/2 clinical trial will be evaluating the safety and the tumor activity of telaglenastat in combination with palbociclib in patients with advanced metastatic PDAC whose tumors harbor mutations in both KRAS and CDK N2A.

Telaglenastat blocks glutamine consumption in tumor cells, which due to specific genetic alterations, such as mutations in KRAS and CDK N2A, often become dependent on increased metabolism of glutamine. Approximately 50% of PDAC patients harbor mutations in both KRAS and CDK N2A.

In preclinical studies with KRAS-mutated cancer models, telaglenastat showed synergistic antitumor effects when used in combination with CDK4/6 inhibitors such as palbociclib, enhancing cell cycle arrest and blocking cancer cell proliferation.

Recently, we announced the initiation of the first clinical trial to evaluate our novel arginase inhibitor in cystic fibrosis. And we are pleased with the enrollment to-date. The depletion of arginine in cystic fibrosis patients by the enzyme arginase results in reduced production of nitric oxide, a key antimicrobial and bronchodilator.

Therefore arginase inhibitors have potential in the treatment of cystic fibrosis. And we have selected CB-280, a unique oral arginase inhibitors solely owned by Caldera, for the treatment of cystic fibrosis. In October, we presented a trial and progress poster describing the trial design at the North American cystic fibrosis conference.

The presentation included preclinical study results, which suggested CB-280, significantly improved lung function and reduced Pseudomonas Aeruginosa colony forming units in preclinical models.

Arginase inhibition with CB-280 resulted in improved central airway resistance and CFTR knockout mice and decreased lung inflection in wild-type and delta 508 CFTR expressing the mice infected with Pseudomonas Aeruginosa.

We have also identified CB-668, an investigational first-in-class potent, orally administered IL-4I1 inhibitor, as a novel immunooncology approach to cancer.

CB 668 is an inhibitor of the enzyme IL-4I1, an enzyme that is expressed by tumor cells and antigen presenting cells, metabolizes phenylalanine, tyrosine and tryptophan to produce hydrogen peroxide, an inhibitor of T cell function.

In particular, IL-4I1 can metabolize tryptophan to kynurenic acid and other metabolites that lead to immunosuppression in the tumor microenvironment.

IL-4I1 expression has been correlated with core outcomes in several tumor types, has a potential role in an immune invasion and may decrease the ability of checkpoint therapy to stimulate an antitumor immune response. IL-4I1 expression is elevated in multiple tumor types with particularly high expression in ovarian and B-cell tumors.

New preclinical data for CB-668 will be presented next week at the Society for Immunotherapy of Cancer virtual meeting. 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 third quarter 2020 were included in today's press release. I will briefly review our results on this conference call. Calithera remains well capitalized. Our cash, cash equivalents and investments were $137.7 million at September 30, 2020.

R&D expenses were $18.2 million for the quarter ended September 30, 2020, compared to $17.2 million for the same period prior year. The increase was primarily due to increase in the telaglenastat and CB-280 programs, partially offset by decreases in the 1158 program and early stage research.

G&A expenses were $4.7 million for the quarter ended September, 30 2020, compared to $3.9 million for the same period prior year. The increase was primarily related to higher personnel- related and facility costs.

Interest and other income net was $0.2 million for the quarter ended September 30, 2020, compared to $0.8 million for the same period prior year, mainly as a result of lower interest rates. Net loss for the quarter ended September 30, 2020, was $22.7 million or $0.32 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] Your first question is from Jonathan Chang with SVB Leerink..

Hi guys. This is David Ruch on for Jonathan. Thanks for taking our questions. First question, just on the IBRANCE combo in pancreatic cancer that you announced yesterday, the press release mentioned there were some encouraging efficacy signals in PDAC patients.

I was just wondering if you could elaborate on any of the clinical data points you've seen and reasons for confidence in the PDAC combination..

Yes. So we enrolled patients across a number of tumor types during the dose escalation and based on activity that we saw there, we certainly were encouraged enough and as was Pfizer to open a cohort. So I am not in a position to really give more information, I think, than that, but that was the basis of the decision..

Okay, great.

And then could you just provide – is there anything else you can provide on the CANTATA timing and the impact of COVID-19 on the data aggregation? I guess, have you seen anything from your trial sites that gives you further confidence in the timeline that you've reiterated today?.

Yes. So as we've talked about previously, COVID has had some impact. And it's largely around the ability to do what's called source data verification, which requires our CRAs to get on-site and look at the data, particularly in Europe.

It's – this has been a process now that we've been working on for months and have been able to, I think, accomplish a lot and address some of those issues. And as we've been seeing the data gets cleaned, and we are increasingly confident in our timeline. So based on what we've seen over the last several months, we remain confident in that timeline..

Great. Thanks a lot, and congrats on the progress..

Yes, thank you..

The next question is from Arthur He with H.C. Wainwright..

My question is also for Arky. I just want to follow-up on the – regarding the pancreas cancer trial.

So just remind us, have you guys decided which is the precancer trial? So just remind us, have you guys decided which is the recommended dose level for the expansion cohort?.

Yes. We – so as with all of our combinations, telaglenastat has been well tolerated, and so we've been able to dose at full dose in combination with IBRANCE..

So is that 800 plus 125 milligrams? That's the – that will be applied to all three expansion cohorts?.

Yes, correct..

Okay. And just a quick follow-up.

So could you – able to elaborate on how large would be the expansion cohort size?.

So the studies are designed similar to other studies that we've designed in terms of expansion cohorts. Actually, the pancreatic study is in the process – the protocol amendments in the process of being finalized. So no comments on that specifically, but it wouldn't be dissimilar to other cohorts that we have designed..

I see. And just a quick one.

So for the pancreas cancer patient, maybe – so is there any requirement for the prior treatment number? Or no? Or they will be all-comer into this expansion cohort?.

Yes. Given that this is an experimental therapy, it's a combination of two therapies that aren't approved, there will be a requirement to have received a prior standard of care therapy. Again, some of those details will be finalized in the amendment, but patients will be expected to have received a standard of care therapy for advanced disease..

Okay. Thank you for that..

Yes, sure..

Our next question is from Matt Phipps with William Blair..

Hi, good afternoon, thanks for taking my question. I was actually really happy to see the product survival trends.

I'm just curious, has there been any kind of just regulatory discussions around them kind of wanting to see a positive trend at least in overall survival? I know PFS is an approvable endpoint in RCC, but there has been one particular TKI that's had some issues, but whether or not they also should survival turn?.

Yes. So you're talking about the cabo combination now for CANTATA – Matt, by the way, so yes. Yes. So we have – and I think we've talked about that in the past, when we've been – we've discussed with FDA as well as European regulators.

And while the primary endpoint is PFS, they will look at the totality of the data, and there is some expectation of OS at least trending in the right direction..

Great. Thanks. And following now we've actually seen the CheckMate 9ER data.

How do you guys think that impacts? I guess, really the question is, do you think a doctor would use this combination if someone had already seen cabo with P1? Or I think there's still plenty of market share even if it's just for people who are refractory and other TK1 refractory.

But I'm just curious if you kind of thought about that at all?.

It's hard to comment on what someone might do. I think from the perspective of our study design, these patients were cabo naive. And so we certainly would expect that to be the label. We think the data looked really good for the 9ER data – for the 9ER study.

And what we've heard is it fits right in there with other therapies that are approved in the frontline. So presumably, there will be some uptake and wasn't – it was not by any means a surprise that the study would be positive. Cabo's a great drug. And we certainly expect that, that would be positive compared to sunitinib.

And – but as you say, given the options available in frontline, we certainly would expect a significant number of patients to come to second-line having not seen cabo yet..

Yes. Great. All right, thanks for answering my question..

Yes. Thanks, Matt..

Your last question is from Mohit Bansal with Citi..

This is James on for Mohit. Just a quick one.

In regards to key stake enrollment, can you assure how many patients have been enrolled since the first patients back in September? And given that COVID seems to be spiking in certain regions, is there any chance – are you seeing any slowdown in enrollment?.

Yes. So I can't speak to the specific number. I can say that it's more than one. We've certainly enrolled multiple patients since that patient enrolled. Given, as is typical with all states that are opening, we're in the process of getting our sites open and so forth. But we're happy with what we're seeing in terms of enrollment so far.

In terms of the impact of COVID, we're not seeing anything at this point. We're not aware of specific issues. Actually, I think from – in Europe, there – and this isn't – KEAPSAKE is only open in the United States. We have seen sites closing down more so in Europe.

But in the U.S., I'm not aware of sites that have been having issues from this current spike in COVID. But certainly, we have our eyes open, and we're talking to our sites, and we'll see how that plays out. But to date, no impact that we're aware of..

Thank you. Appreciate it..

Yes. Thanks, James..

There are no further questions. I will now turn the call over back to Jennifer McNealey..

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

That concludes today's conference. You may now disconnect..