Q2 2019 | CALA Message Board Posts

Calithera Biosciences, Inc.

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Msg  2688 of 2688  at  8/9/2019 12:50:17 PM  by

Pacific


Q2 2019

https://www.seekingalpha.com/article/4283608-calithera-biosciences-inc-cala-ceo-susan-molineaux-q2-2019-results-earnings-call-transcript?

Susan Molineaux

Thanks, Jennifer. Good afternoon, everyone, and thank you for joining us today on our second quarter 2019 conference call. 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 currently have 4 programs in our pipeline, and our productive R&D team continuously evaluates new targets and new molecules for consideration as novel development candidates.

In the second quarter, we achieved clinical proof-of-concept for our glutaminase inhibitor, telaglenastat, with positive top line results of the randomized Phase II ENTRATA study. With the completion of the secondary offering in this quarter, we believe we are well positioned to execute on our strategy and advance our pipeline forward. This positive Phase II ENTRATA proof-of-concept study is our first randomized study with telaglenastat and by demonstrating that telaglenastat is as active as the treatment for clear cell renal cell carcinoma, or RCC, provides validation for our lead program. Combined with everolimus, telaglenastat doubles the median progression-free survival compared to everolimus with placebo in heavily pretreated patients with renal cell carcinoma.

It reduced the risk of death or disease progressions by 36%. In addition, consistent with our previous clinical experience, telaglenastat had a well-tolerated safety profile in combination with everolimus. Telaglenastat is the first selective glutaminase inhibitor to enter the clinic and is now the first to demonstrate clinical activities for the treatment of cancer. Based on the compelling activity observed in this randomized proof-of-concept study, we believe telaglenastat has the potential to provide a novel treatment option for patients and physicians treating RCC and potentially in the future, patient with other cancers.

Tumor metabolism has been a focus of our company since its inception. Telaglenastat blocks the metabolism of glutamine, a key pathway for the growth and survival of many cells. Signal transduction inhibitors, such as everolimus and an inhibitor of mTOR for cabozantinib, a tyrosine kinase inhibitor, or TKI, blocks the metabolism of glucose in many cancer cells. Dual inhibition of glucose and glutamine metabolism results in synergistic antitumor activity as demonstrated in preclinical tumor models. Based on this common mechanism of action, telaglenastat has the potential to be combined with either TKI or mTOR inhibitors, two classes of drugs that are used to treat RCC today. We're excited about the results in the ENTRATA trial, showing that telaglenastat is active in weak part renal cell carcinoma. That is of particular importance to us because we are continuing to invest in RCC.

We are currently enrolling a second larger RCC trial combined in telaglenastat with cabozantinib. That trial called CANTATA, is a global randomized double-blind, placebo-controlled pivotal trial designed to evaluate the efficacy and safety of telaglenastat in combination with cabozantinib. CANTATA will enroll approximately 400 patients and is designed to be a potential registration trial. We are on track to enroll CANTATA by year-end and to report top line results in the second half of 2020.

We also continue to invest in telaglenastat beyond renal cell carcinoma. We have broadened our clinical development program for telaglenastat to two new clinical trial collaborations with Pfizer as well as multiple investigator-sponsored trials, or IST. In addition, telaglenastat is part of a broad NTI-sponsored CTEK clinical investigation program. Our internal drug discovery team continues to produce novel drug candidates with the potential to be highly differentiated new therapies in areas of unmet needs. Our 2 new internally discovered novel small molecule drug candidates are both entering clinical development in 2019.

The first one is CB-280, an oral arginase inhibitor for the treatment of cystic fibrosis, which is already in Phase I study. And the second one is CB-708, an oral small molecule CD73 inhibitor for the treatment of cancer. As our programs move forward in development, we look forward to a number of important milestones. In the second half of the year, we look forward to completing enrollment in our registrational CANTATA trial, evaluating telaglenastat for the treatment of patients with renal cell carcinoma as well as the presentation of data from our arginase inhibitor program, INCB001158, at the 2019 ESMO Conference in Barcelona.

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

Keith Orford

Thank you, Susan. Let's begin with a more detailed update on telaglenastat, our glutaminase inhibitor and our most advanced product candidate. We're currently focused on forging a clinical and potentially commercial path for telaglenastat in renal cell carcinoma. The program includes two randomized clinical trials of telaglenastat for the treatment of RCC. As Susan mentioned, the Phase II ENTRATA trial of telaglenastat, in combination with everolimus in late-line patients, recently met its primary endpoint of progression-free survival, as noted in our top line results announcement in June. The achievement of positive top line results and our first randomized trial is a significant milestone for us because it provides the first proof-of-concept for our lead compound, telaglenastat.

In the trial, telaglenastat met its primary endpoint in doubled medium progression-free survival in heavily pretreated patients with advanced renal cell carcinoma when added to everolimus versus everolimus with placebo. We plan to submit the results for presentation at a medical meeting and can better update you on timing in the future. We are also actively enrolling CANTATA, a global trial of telaglenastat in combination with cabozantinib in second and third line RCC patients.

CANTATA is a randomized placebo-controlled trial in approximately 400 patients and has registration potential. It 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 1 or 2 prior lines of therapy, including at least 1 prior anti-angiogenic agent or the ipilimumab/nivolumab combination. Patients are being randomized in a one-to-one ratio to either telaglenastat plus cabozantinib or placebo plus cabozantinib. Patients will be stratified by IMDC risk category and prior treatments with anti-PD-1, PD-L1 therapy. The prior -- the primary endpoint is progression-free survival by independent review, overall survival will be assessed as a key secondary endpoint.

We are pleased with the enrollment rate of the trial, and we remain on track to report top line results of CANTATA in the second half of 2020. Late last year, we announced 2 new clinical trial collaborations to evaluate Pfizer's CDK4/6 inhibitor, palbociclib, also known as IBRANCE, and the PARP inhibitor, talazoparib, also known as TALZENNA, each in combination with Calithera's glutaminase inhibitor, telaglenastat.

Preclinical data suggests that telaglenastat synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage and block cancer cell proliferation in both HRD-positive and HRD-negative cancer models. We recently initiated a Phase I/II clinical trial with a combination of telaglenastat plus talazoparib in patients with RCC and TNBC. The trial will evaluate the potential of telaglenastat's sensitized tumors to talazoparib in patients, regardless of mutations in the BRCA gene. Telaglenastat also synergizes with CDK4/6 inhibitors by enhancing cell cycle arrest and blocking cancer cell proliferation.

In July, we opened a Phase I/II clinical trial of the combination of telaglenastat plus palbociclib in patients with KRAS-mutated colorectal cancer, CRC, and patients with KRAS mutated non-small cell lung cancer, NSCLC. We are pleased that each of those protocols are now open and enrolling patients into the dose escalation cohorts. Next, the arginase program. IMCB001158, also known as 1158, is an investigational first-in-class immuno-oncology metabolic checkpoint inhibitor targeting arginase and 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. The program is progressing well and is actively enrolling multiple 1158 trials. The first trial we would like to highlight is evaluating 1158 as a monotherapy and in combination with pembrolizumab. The second clinical trial is evaluating 1158 in combination with each of 3 chemotherapy regimens; FOLFOX, gemcitabine/cisplatin or paclitaxel. Primary endpoints include safety and objective response rate. We and our partner, Incyte, plan to present solid tumor data in an oral presentation at the ESMO meeting in late September. CB-280 is a novel arginase inhibitor in the development -- in development for treatment of cystic fibrosis. Under our collaboration agreement with Incyte, we retained worldwide rights to develop arginase inhibitors in specific nononcology rare disease indications, including cystic fibrosis. Arginase has been proposed to be critical in the pathophysiology of cystic fibrosis and several other nononcology 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, is known to have potent antimicrobial activity and 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. In February, we announced that we filed an IND application for CB-280 with the U.S. FDA and initiated a Phase I clinical trial. This first-in-human Phase I trial, which we plan to complete this year is evaluating the safety, tolerability and pharmacokinetic profile of oral CB-280 in healthy volunteers. Our next oncometabolism drug candidate is CB-708, an orally bioavailable small molecule inhibitor of CD73, an enzyme in the immunosuppressive adenosine pathway.

CD73 suppresses immune activation by converting extracellular ATP into adenosine. CB-708, a potent oral inhibitor of CD73, has both single-agent activity and activity in combination with anti-PD-1 and standard chemotherapy in preclinical animal models. We plan to initiate clinical studies with CB-708 in 2019.

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

Stephanie Wong

Thank you, Keith, and good afternoon, everyone. Detailed financial results for the second quarter of 2019 were included in today's press release. I will briefly review our results on this call. Calithera ended the quarter well capitalized, following our secondary offering in June, in which we raised gross proceeds of $58 million. We believe our cash position enables us to drive our clinical programs to meaningful value inflection points. Cash and investments were $153.2 million at June 30, 2019.

R&D expenses were $20.9 million for the quarter ended June 30, 2019, compared with $17.3 million for the same period prior year. The increase of $3.6 million was primarily due to a $1.5 million increase in the telaglenastat program, including our CANTATA trial, an increase of $1.5 million in the 1158 program, and an increase of $0.7 million in the CB-280 program. G&A expenses were $4 million for the three months ended June 30, 2019, compared with $3.5 million for the same period prior year.

The increase of $0.5 million was related to higher professional services costs. Net loss from operations for the 3 months ended June 30, 2019, was $24.2 million or $0.58 per share. And with that, I will now turn the call back over to Susan.

Susan Molineaux

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

Question-and-Answer Session

Operator

[Operator Instructions]. And our first question coming from the line of Jonathan Chang from SVB Leerink.

Jonathan Chang

Congrats on all the progress. First question, can you help us at expectations ahead of the ESMO presentation for the arginase program in terms of how much data and how mature the data will be?

Keith Orford

Yes, so will be presenting data from the 101 study. And just to remind you the 101 study is studying 1158 and monotherapy as well as the pembrolizumab combination across a variety of cohorts. So we will be presenting monotherapy data, monotherapy cohorts as well as the -- some of the combination cohorts. Just as a reminder, the study continues to enroll. And so we will present data on a subset of the cohorts based in part on the maturity of this data.

Jonathan Chang

Got it. Second question, on the recent positive ENTRATA update, can you help us contextualize the data disclosed in terms of the patient population in the study? And how should we be thinking about historical benchmarks for everolimus?

Keith Orford

Right. So yes, this is a very heavily pretreated pro prognosis population. And so these were -- most of these patients had received 2 prior tyrosine kinase inhibitor therapies. They were weighted towards intermediate and core diagnostic categories and in general, were just heavily pretreated relative to data that have been previously published. So this was the, I would say, the first data set in this new population of patients receiving everolimus. Prior data would have suggested something in the range of 3.5 months for the PFS for everolimus in the second-line populations. And this was again, later line, more heavily pretreated. And so that -- so the result of approximately two months PFS actually was not a surprise to our investigators when we reviewed the demographics. In fact, we reviewed the demographics prior to having the actual data on blind and then, they let us know that it's likely going to be a short PFS for this population.

Jonathan Chang

Got it. And when can we expect to see a presentation of the ENTRATA data?

Susan Molineaux

So our practice is to submit data to a medical meeting and then disclose exceptions to -- in line with the meeting of embargo policy. So when we have more information, we will let you know. But we plan to disclose more data, either in coming months of this year or the first quarter of next year.

Jonathan Chang

Got it. And just 1 last question. Any guidance on cash runway post the recent offering?

Stephanie Wong

We haven't updated guidance. But as you know, we ended the year at $136.2 million. And at that time, we expect to utilize cash of $75 million to $85 million. So that was back in January. The guidance hasn't been updated and that didn't include the $58 million that we just raised in June. However, I can say we are well capitalized to continue to meet these milestones in each of our 4 programs, including the CANTATA trial.

Operator

Our next question coming from the line of Mohit Bansal with Citigroup.

Mohit Bansal

Congrats on all the progress from my side as well. If I may ask 1 question related to the ENTRATA study. And how should we compare in contrast the patient population, which you are enrolling in ENTRATA versus CANTATA? And then can you just remind us again about the following of the CANTATA study. What you're expecting from the control arm there?

Keith Orford

So the second question, I think I missed.

Mohit Bansal

Its related to the powering of the study, how you are powering CANTATA study? And how you are assuming control arm? What are you assuming for control versus treatment arm there?

Keith Orford

Okay. Yes. Great. So yes. So the patient populations between these 2 studies are similar. And that's above RCC -- clear cell RCC patients, but they are significantly less pretreated in the CANTATA study. So we're focused on really where the CANTATA -- I'm sorry, where cabozantinib is currently approved, which is primarily in the second-line setting. So these patients are required to have received 1 or 2 prior therapies. So there is second or third line. They will have received, I see a 0 -- prior TKIs, if they had previously received the ipilimumab/nivolumab I/O combination in frontline or they could have received 1 or 2 TKIs. So 0 to 2 prior TKIs. We would expect most of these patients -- at least, many of these patients to have received prior I/O and -- but less heavily pretreated in terms of prior TKIs. In terms of the control arm, this is a similar population to the METEOR study. And in the METEOR study, the cabozantinib PFS was in the range of 7.5 months.

There are some differences. Again, we have some subset of patients will have -- be coming in straight off of ipi/nivo. And those patients should might expect to do somewhat better than historical data. On the other hand, we also -- there are other factors that play in terms of what the distribution of prognostic categories are and so forth. So it's hard to predict. But we're expecting will be somewhat longer, maybe slightly longer than what we're seeing in the METEOR study, but probably not substantially.

Mohit Bansal

Got it. And if I may ask one more. Did the arginase data, coming at ESMO, should we expect monotherapy responses with this kind of agent? Or do you think the responses will be more pronounced in the combination setting from mechanism of action.

Keith Orford

Yes. Our feeling has been that this would be -- this agent as an I/O therapy, as most new I/O therapies being developed are more likely to be active in combination with PD-1. And so that's really our primary focus in terms of our development plan. So that's really where I would focus. But we -- But I would say, responses are that of the question. And I think if you were to see responses, I think it would be nice proof-of-concept for the molecule and nice support that arginase inhibition on its own has activity. But we'll be able to talk more about that at ESMO.

Operator

And our next question coming from the line of Matt Phipps with William Blair.

Matthew Phipps

One on the arginase program. Jusy how much data is in the abstract? Since obviously that will be coming first, it's more of a placeholder? Is there actual kind of results in there, I believe, they are coming towards the end of September, a little before the conference itself?

Susan Molineaux

I think that the abstract is indicative and focuses on most of the data that we'll be talking about and of course, there will be an update for a couple of months. And it is an ongoing trial, so it's somewhat fluid and depends upon what we see as we get closer to ESMO. But I think the abstract's focus will be similar to the focus of the presentation.

Matthew Phipps

So I know you guys are still trying to figure out where to bring the ENTRATA results, so lots will depending on that. But do you think the full data presentation will have and look at the overall survival results? I know they weren't yet matured when you guys top lined it couple of months ago.

Keith Orford

Yes it -- again, we'll present -- we'll present the OS data when they're mature. And so the timing of the presentations may impact whether or not OS data will be presented, but it's certainly possible that OS data will be in that presentation.

Matthew Phipps

Got it. And then lastly, I want to get your thoughts on the palbociclib combo in the KRAS-gene populations, particularly given now the recent AMG 510 results and just kind of activity in this space with some of these inhibitors. Obviously, may be that's only one specific KRAS mutation. So maybe that's kind of an angle you can take, but just curious how you're thinking about that landscape, I guess.

Keith Orford

Yes. Obviously, the data has been impressive, but they are restricted to a specific KRAS mutation. And it is -- there is a unique aspect of the binding site that makes them particularly susceptible. And so whether or not other KRAS mutations will be as susceptible to inhibition, I think it's an open question. So we're still confident that KRAS remains an important unmet need. And as you know, it's one of the most frequently mutated omni genes in cancer, and we continue to remain interested in and at the target population.

Matthew Phipps

Do you think we see some data from initial data from the 2 Pfizer combo studies next year?

Keith Orford

So the design of the study is going to be open-label dose escalation followed by open-label expansion cohorts. So I would think it's possible that by the end of the year, we might have some data that we can present, but it's early right now to know . But obviously this is not a blinded randomized study. So it's possible that we would be able to do that by the end of next year.

Matthew Phipps

And last question. Obviously, this year, positive ENTRATA results plus also expansion to two novel combinations. Especially on the back of the positive trial results, this true randomized data. Do you see looking for additional indications with telaglenastat, additional combinations? Or kind of happy with the trials ongoing right now? I want to see the CANTATA results. Where do you think broad strategy wise for the next year?

Susan Molineaux

That's a good question, Matt. We are continuing to look at other possible trials to start in, 1 probably of the highest of interest to us is continuing to examine the pathway, the key nerve pathway that's involved in managing oxidative stress and glutathione synthesis, taking care of where we and others have data saying that, that's the population that's quite glutaminase sensitive. And in addition, Intrusive had an interesting presentation at ASCO, looking back retrospectively at lung cell trials, showing that this population serves poorly on current therapies, both PD-1 and chemotherapies. So -- and we're aware of that data, and we are considering possible ways to address questions in trials in the future.

Operator

Our next question coming from the line of Jim Birchenough with Wells Fargo.

Nicholas Abbott

It's Nick on for Jim this afternoon. First question would be on 280. What did the first CF trial look like? And when do you expect to start that trial?

Susan Molineaux

The question was -- it's a little hard to hear, was -- I'll just confirm it. When is the first cystic fibrosis trial starting and the design of this trial?

Nicholas Abbott

Yes, I mean, when is that trial -- yes, what does the trial look like? And when would you think you'll be able to start that trial?

Keith Orford

Right. So as we mentioned, we're currently running studies in healthy volunteers and evaluating safety and PK and so forth. Patient studies will include patients, CF patients, irrespective of their mutation status, so we'll be able to enroll patients across all CF mutation backgrounds. And irrespective of their current therapy on the CFTR modulators. So population will be broad, and we'll include evaluation of safety like renal dose escalation as well as an evaluation of both biomarkers and sort of your endpoints of that business .

Nicholas Abbott

I guess is that something you think you can start early next year or first half of next year?

Keith Orford

Yes. I think, that's a reasonable assumption.

Nicholas Abbott

Okay. And then on 708, obviously CD73 inhibitors that...

Susan Molineaux

Dropped off.

Operator

Okay. I am showing he just removed himself from the queue.

Susan Molineaux

Probably dialing through.

Jennifer McNealey

We can give him one more minute to dial in.

Operator

[Operator Instructions]. Our next question is coming from the line of Jonathan Chang with SVB Leerink.

Jonathan Chang

Just a quick question to fill the void. Can you provide any color on how enrollment in the CANTATA study is going? Has the pace of enrollment been sort of consistent with your plans initially?

Keith Orford

Yes. We've been very happy with enrollment across all regions. So yes, I would say we are on track.

Operator

And at this time, I'm showing no further questions. I would like to turn the call back over to Jennifer McNealey for closing remarks.

Jennifer McNealey

Thank you, Olivia. And thank you all for joining us today. Have a great evening.

Operator

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may all disconnect. Everyone, have a great day.





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