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spk09: And welcome to the Caldera Biosciences Fourth Quarter 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference to your speaker today, Jennifer McNeely, VP Investor Relations. Please go ahead, ma'am.
spk06: Thank you, Joelle. Good afternoon, everyone. Welcome to our year-end 2020 conference call. Joining me today are Susan Molyneux, our founder, president, and CEO, Keith Orford, chief medical officer, and Stephanie Wong, chief financial officer. We have issued our press release, and it can be accessed through our website at calathera.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 provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ material 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 10Q, followed by 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.
spk07: Thank you, Jennifer. Good afternoon, everyone, and thank you for joining us today on our fourth quarter and year-end 2020 conference call. On behalf of the entire team, I'd like to say we hope that you and your friends and families remain healthy. 2020 was a challenging year for nearly everybody as we faced new challenges in public health. Despite the challenges we faced, we are quite hopeful for the future. At Califera, 2020 was a year of execution. We successfully completed and reported results of our global randomized trial in renal cell carcinoma early in 2021 while advancing our pipeline of novel therapeutics. 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, particularly towards helping us achieve our goal of reporting top-line results of the Kantata trial in January. We're both appreciative and proud of our entire team for accomplishing a number of challenging goals. And while we are disappointed in the results of the Kantata trial, we remain enthusiastic for the potential of glutaminase inhibition to be a novel approach to the treatment of cancer. And we remain committed to our mission of being an integrated biotechnology company that develops novel small molecule on co-metabolism 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 continuing to develop teleglanostat, and we are enrolling the randomized keepsake trial in first-line non-small-cell lung cancer patients harboring genetic mutations in KEEP or Nrf2. We also continue to evaluate teleglanostat in multiple indications, including investigator-sponsored trials. Our partnered Arginase Inhibitor Program is ongoing with Insight, where we have a number of clinical trials evaluating CB1158 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, 2020, as permitted under the terms of the INSIGHT agreement, in order to focus our resources on our own internal development programs. As a result of our decision to opt out, INSIGHT will pay all costs to develop 1158. Arginase inhibitors also have potential in the treatment of cystic fibrosis. And accordingly, we selected CB280, a unique oral arginase inhibitor, for the treatment of this patient population. In November 2020, we announced that we were awarded up to $2.4 million from the Cystic Fibrosis Foundation to support clinical development of CB280. And we are grateful to the Cystic Fibrosis Foundation for their support, and we're 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 program.
spk13: Thank you, Susan. Let's begin with a more detailed update on Telaglenostat, our glutaminase inhibitor in development for the treatment of first-line lung cancer. in patients with KEEP1 Nrf2 mutations. Mutations in the KEEP1 Nrf2 pathway, which occur in an estimated 20% of non-small cell lung cancer patients, are associated with aggressive disease. Numerous recent reports of clinical data have demonstrated that activation of this pathway, either through the loss of KEEP1 function or activation of Nrf2, are associated with poor clinical outcomes among patients with non-small cell lung cancer, receiving frontline standard of care therapies, including chemotherapy, immunotherapy, and chemoimmunotherapy. Preclinical models have shown that activation of the KEEP1 Nrf2 pathway makes tumors dependent on glutaminase activity for growth and survival, making these tumors exquisitely sensitive to inhibition of glutaminase activity by teloglenostat. The double-blind teloglenostat trial, known as KEEPstake, enrolled the first patient in September 2020 and will enroll approximately 120 patients. Eligible patients are newly diagnosed with stage 4 non-squamous non-small cell lung cancer with tumors that have the KEEP1 or Nrf2 mutation. Patients will be randomized to receive teloglanosad or placebo in combination with pembrolizumab, carboplatin, and pemetrexed. The study will evaluate the safety and investigator-assessed PFFs of telglenostat plus this standard-of-care chemoimmunotherapy regimen. We plan to share interim data from this trial in the second half of 2021. We are also conducting an exploratory Phase 1b2 trial in collaboration with Pfizer, combining telglenostat with iBrandt. In 2020, 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 CB280, a unique oral arginase inhibitor solely owned by Calthera, for the treatment of cystic fibrosis. In October 2020, We presented a trial-in-progress poster describing the trial design at the North American Cystic Fibrosis Conference. The presentation included preclinical study results which suggest CB280 significantly improved lung function and reduced Pseudomonas aeruginosa colony-forming units in preclinical models. Arginase inhibition with CB280 resulted in improved central airway resistance in CFTR knockout mice and decreased lung infection in wild-type and Delta F508 CFTR-expressing mice infected with Pseudomonas aeruginosa. We plan to share data from this trial in the second half of 2021. We've also identified CB668, an investigational, first-in-class, potent, orally administered IL4I1 inhibitor as a novel immuno-oncology approach to cancer. CB668 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. IL-4I1 expression has been correlated with poor outcomes in several tumor types, has a potential role in immune invasion, and may decrease the ability of checkpoint therapy to stimulate an anti-tumor 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 CB668 was presented in November 2020 at the Society for Immunotherapy of Cancer virtual meeting. With that, I'll pass it over to Stephanie for an update on our financials.
spk10: Thank you, Keith, and good afternoon, everyone. Detailed financial results for the fourth quarter near end of 2020 were included in today's press release. I will briefly review our results on this call. Califera remains well capitalized. Our cash, cash equivalents and investments were $115.2 million on December 31st, 2020, which we believe will be sufficient to meet our current operating plan through 2022. R&D expenses were $71 million in 2020 compared to $76.3 million in 2019. The decrease was due to a 6.2 million decrease in the 1158 program and a 3.8 million decrease in early-stage research, partially offset by an increase of 2.7 million in the teleglanostat program and an increase of 2.0 million in the CB280 program. R&D expenses for the fourth quarter of 2020 were 17.1 million compared to 17.9 million for the same period last year. DNA expenses were 20.4 million in 2020, compared to $16.6 million in 2019. The increase was primarily related to a $2.5 million increase in personnel related and facility costs and a $1.3 million increase in professional services. DNA expenses for the fourth quarter of 2020 were $5.6 million compared to $4.6 million for the same period last year. Interest and other income net was $1.3 million in 2020 compared with $3 million in 2019. Interest and other income net for the fourth quarter of 2020 was $0.1 million compared to $0.7 million for the fourth quarter of 2019. Net loss for the quarter in December 31, 2020 was $22.6 million. And with that, I will now return the call back over to Susan.
spk07: Thank you, Stephanie. And with that, Joelle, we're happy to open the line for questions.
spk08: Thank you.
spk09: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Mohit Banzal with Citi. Your line is now open.
spk18: Hey, good afternoon, guys. This is James on for Mohit. Thanks for the update and taking the question. First question, any color on the enrollment progress for Keepsake? I know we're on track for data later this year, but can you Give us a little bit of numbers at this point, or is that still sort of a work in progress? And then related to keepsake, there was recently some data from a KRAS inhibitor showing that STIC11 mutation patients had a higher response to the KRAS inhibitor. And I know that you guys have previously mentioned that the keepsake trial will have a good proportion of STIC11 patients. So I was wondering if Calthera has looked at combining TEL11 stat with any KRAS inhibitors.
spk13: Yeah. Hi, James. This is Keith. In terms of enrollment, so as we said, we're planning to enroll and make public some data from the initial interim analysis later this year. I think enrollment has been, I would say, impacted by COVID. I think if you probably asked anyone, there has been some impact from COVID, but it's something we're working through and we remain confident in our timeline to be able to get to data on that interim analysis later this year. So definitely some impact, but something that we are working through. In terms of the KRAS story, it's definitely one we're quite interested in, and that's sort of a, I guess I would say, a work in progress, something we're looking into on our side, but an area of a lot of interest. I mean, I think there's been a couple of different reports on the impact of STIC11 that actually between the two clinical KRAS inhibitors that were somewhat different. So that'll be interesting to see how that plays out. But that definitely remains a combination of interest.
spk02: Appreciate it, guys. Thank you so much.
spk09: Thank you. Our next question comes from Matt Pitts with William Blair. Your line is now open.
spk04: Thanks for taking my question. I guess just kind of a follow-up on that interim. I mean, this will be an interim for PFS, I assume, right, as opposed to maybe just response rates. And, Keith, are you still thinking a PFS in the control arm of around seven months, or has there been any data lately to change that assumption?
spk13: So, yeah, in terms of the assumptions, we've actually been – for this population, so for the keep one mutant population, the data that have been, you know, reported in a few different places put that probably the median somewhere in the three to five month range. So, and this is in front line. So, these patients do very poorly. And so, that's, you know, that's what we're assuming. And yeah, in terms of the data that we would be talking about, you know, it's probably a combination of PFS as well as response rates. You know, the data will be, you know, it's going to be an interim analysis, and the data will still be kind of maturing. So we're not going to be talking about fully mature data, but we do, given the short, you know, the short expected PFS, medium PFS for the control arm, we would expect to, you know, hopefully see some, you know, see some daylight between the two curves and be able to see a trend in the right direction there.
spk04: Thanks, Keith. And any chance we see an update from that iBrants combo in Tinker Addict this year?
spk13: You know, we haven't gotten on that. I think it's a little hard to say exactly when. It'll likely be this year or next, but... You know, that study really just started enrolling, so, you know, I think it's too early to say with certainty.
spk11: Thank you. Yep. Thank you.
spk09: Thank you. Our next question comes from Jonathan Chang with SVB Lyric. Your line is now open.
spk03: Hi, guys. Thanks for taking my questions. First question, can you provide your latest thoughts on how much and how mature the second half Yeah, hey, Jonathan.
spk13: Yeah, you know, in terms of the, we're expecting somewhere in the range of, you know, 40 to 50 patients' worth of data by the end of the year, and I think that's kind of the ballpark. As we've talked about before, the analysis is not explicitly defined in the protocol and having a specific sort of statistically driven endpoint or analysis. It's not a futility analysis. It's not an early efficacy analysis. It's an administrative interim that allows us to have an early look at the data and react as appropriate, which could mean any number of things, reaching out to regulators, starting to prepare for a subsequent study. So, that's the, you know, kind of the spirit of the interim. And, you know, in terms of maturity, you know, I guess I would say obviously patients who are enrolled later, you know, as we get closer to the interim analysis, those patients will be more likely to be, you know, to be censored and have less mature data. The hope is to have, you know, hopefully a couple of scans for those patients. so that we can get a feel for the median PFS. As we talked about, the median is in the range of three to five months for the control arm, we would expect. So if we can start to see separation at that early time point, that would be encouraging.
spk03: Got it. Thank you. And last question, how are you thinking about potential business development opportunities for your pipelines?
spk07: Well, this is Susan. Hi, Jonathan. In general, we remain open to partnering opportunities as one of several ways to continue to develop our pipeline. We will read out this year the first data in cystic fibrosis patients, and we have a clear picture of where we might go next. if that data look encouraging and there might be, you know, a partnering opportunity somewhere along the cystic fibrosis development timeline. And as you know, we do have earlier stage pipeline assets that are IND ready. We have a CB73 small molecule oral inhibitor, and we also have an inhibitor for IL-4I1. And, you know, Partnering is a possibility for those as well. And for Teleconstat, we'll wait and see what develops. But we're always open to partnering at the right time for the right reasons.
spk03: Got it. Thanks for taking my questions.
spk09: Thank you. Our next question comes from Arthur Heath with HC Wainwright. Your line is now open.
spk16: Hey, good afternoon, everyone. Thanks for taking my question. So I have two. So regarding the Keepsake study, maybe I missed. Could you give us some color on the regarding enrollment? And second, regarding the Phase 1-2 study of Telegram in company with the in-brands, could we expect any data updated this year? Thank you.
spk13: Yeah. Hi, Arthur. In terms of enrollment for keepsake, while we don't usually get specific numbers of patients enrolled, I did mention that there has been some impact from COVID. I think it's probably multifactorial, both at the level of the sites who have staff impacted in various ways, as well as patients, since this is a frontline study, And, you know, patients getting diagnosed in the frontline setting is necessary for patients to be enrolled through the study. So, I mean, I think there are ways in which COVID is impacting clinical studies and we're, you know, we're, you know, like everyone else, experiencing that. But, you know, as I mentioned, you know, we still remain on track, we think, for data by the end of the year. And then in terms of the IBRANTS study, that study is enrolling and we're monitoring the data there. No real update there from an enrollment perspective. I think we talked about data probably either this year or next with that study, but hard to be more specific than that at this point.
spk15: Thank you. Thank you for taking my question.
spk01: Mm-hmm. Thank you.
spk09: Thank you. Our next question comes from Matt Pipps with William Blair. Your line is now open.
spk04: Hey, coming back on. Thanks, Keith. You know, Keith, I was wondering if we could talk just to walk through some, I guess, hypothetical next steps after this interim. So, you know, obviously you'll present the data later. depending on, you know, the level of activity, but is it, you know, okay, maybe we go take it to the FDA, or is it, okay, we're just going to continue to let the trial run out, or is there a, does the trial have some kind of built-in adaptation to expand enrollment to maybe make it pivotal if things are looking good? Just curious, you know, what kind of potential next steps there are after this interim look?
spk13: Yeah, so that's a great question, and those are the kinds of things we're thinking about. For example, we can always reach out to FDA with the data if they're compelling and for example, talk about breakthrough designation, talk about either amending the current study or starting the planning for subsequent pivotal phase three. So those are the kinds of things that by looking early, we can kind of get a start on what we think the best path And, again, all of those are really options, and probably, you know, an interaction, you know, with FDA would be, you know, part of that if we were looking to move forward with, you know, an accelerated sort of path to approval in some way.
spk04: Do you imagine trying to reach out to the FDA would occur before you even present the data given, you know, abstract submission timelines?
spk13: I would say interacting with the FDA is independent of any kind of presentation at a meeting. I wouldn't link those to each other. Frankly, what we're talking about isn't necessarily even a ... I think what we've talked about in the past is that this may or may not be an actual conference presentation, or maybe a prelude to a conference presentation. that the discussion this year wouldn't necessarily be in the context of a conference.
spk04: Got it. Okay. Thanks, Keith.
spk13: Yep. Thanks, Matt.
spk09: Thank you. I'm not showing any further questions. And our next question comes from Nick Abbott with Wells Fargo. Your line is now open.
spk17: Good afternoon. Thanks for taking my question. And I apologize, I missed nearly all of the prepared questions. Remarks. So I'm going to ask a question on the NCI study of Covital and Statin to the RISO. You know, I know you may not have a lot of insight into that trial, but it was updated end of January. They're still talking about having data in June. So do you have any insight into that trial? Is this a way also to help de-risk keepsake in some of these patients may also have a keep-on mutation?
spk13: Yes, so actually, you know, as we talk about, oftentimes, hi, Nick, by the way, we don't have any real insight at this point that we can share on the study. So, you know, I think it's an interesting question, whether it's, you know, about key mutant patients or just looking at the combination with TKIs targeting driver mutations. I think it's an interesting study. and we look forward to learning more about it. But at this point, you know, it's not something that we're, you know, we're able to, you know, to speak to.
spk17: Okay. Thanks. And then just, I know there have been a few questions on the iBrands combination. Can you remind us when the colorectal and non-small cell lung cohorts were open for the KRAF mutations, and is that the data you're referring to as possibly being available by the end of this year or beginning next?
spk13: So that's a good question. You're testing my memory of when the study opened, and I'm not sure I'm going to be able to answer that accurately without looking it up. So I apologize. I can say the pancreatic cohort opened more recently. So that was one that we added to the study by amendment. So that was, I think, opened late last year. But the timing of the colorectal and lung cohorts opening, I don't know if I can answer that for you as we sit here. I will say, though, that the data that we could present could be those data and the pancreatic. I think data from any or all of those cohorts is possible. But we will get back to you on the timing of that at the start of the study. I'm sure I should have that ingrained in my head somewhere.
spk09: Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Jennifer McNeely for closing remarks.
spk06: Thank you, Joelle, and thanks all for joining us today. Have a great evening.
spk09: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Thank you. Thank you. Bye. Thank you. Thank you. you you Ladies and gentlemen, thank you for standing by, and welcome to the Calder Thera Biosciences Fourth Quarter 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference to your speaker today, Jennifer McNeely, VP Investor Relations. Please go ahead, ma'am.
spk06: Thank you, Joelle. Good afternoon, everyone. Welcome to our year-end 2020 conference call. Joining me today are Susan Molyneux, our founder, president, and CEO, Keith Orford, chief medical officer, and Stephanie Wong, chief financial officer. We have issued our press release, and it can be accessed through our website at calthera.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 provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ material 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 10Q 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.
spk07: Thank you, Jennifer. Good afternoon, everyone, and thank you for joining us today on our fourth quarter and year-end 2020 conference call. On behalf of the entire team, I'd like to say we hope that you and your friends and families remain healthy. 2020 was a challenging year for nearly everybody as we faced new challenges in public health. Despite the challenges we faced, we are quite hopeful for the future. At Califera, 2020 was a year of execution. We successfully completed and reported results of our global randomized trial in renal cell carcinoma early in 2021 while advancing our pipeline of novel therapeutics. 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, particularly towards helping us achieve our goal of reporting top-line results of the Kantata trial in January. We're both appreciative and proud of our entire team for accomplishing a number of challenging goals. And while we are disappointed in the results of the Kantata trial, we remain enthusiastic for the potential of glutaminase inhibition to be a novel approach to the treatment of cancer. And we remain committed to our mission of being an integrated biotechnology company that develops novel small molecule on co-metabolism 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 continuing to develop teleglanostats, and we are enrolling the randomized keepsake trial in first-line non-small-cell lung cancer patients harboring genetic mutations in KEEP or Nrf2. We also continue to evaluate teleglanostat in multiple indications, including investigator-sponsored trials. Our partnered Arginase Inhibitor Program is ongoing with Insight, where we have a number of clinical trials evaluating CB1158 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, 2020, as permitted under the terms of the INSIGHT agreement, in order to focus our resources on our own internal development programs. As a result of our decision to opt out, INSIGHT will pay all costs to develop 1158. Arginase inhibitors also have potential in the treatment of cystic fibrosis. And accordingly, we selected CB280, a unique oral arginase inhibitor, for the treatment of this patient population. In November 2020, we announced that we were awarded up to $2.4 million from the Cystic Fibrosis Foundation to support clinical development of CB280. And we are grateful to the Cystic Fibrosis Foundation for their support, and we're 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 program.
spk13: Thank you, Susan. Let's begin with a more detailed update on Telaglenostat, our glutaminase inhibitor in development for the treatment of first-line lung cancer. in patients with KEEP1 Nrf2 mutations. Mutations in the KEEP1 Nrf2 pathway, which occur in an estimated 20% of non-small cell lung cancer patients, are associated with aggressive disease. Numerous recent reports of clinical data have demonstrated that activation of this pathway, either through the loss of KEEP1 function or activation of Nrf2, are associated with poor clinical outcomes among patients with non-small cell lung cancer, receiving frontline standard of care therapies, including chemotherapy, immunotherapy, and chemoimmunotherapy. Preclinical models have shown that activation of the KEEP1 Nrf2 pathway makes tumors dependent on glutaminase activity for growth and survival, making these tumors exquisitely sensitive to inhibition of glutaminase activity by teloglenostat. The double-blind teloglenostat trial, known as KEEPstate, enrolled the first patient in September 2020 and will enroll approximately 120 patients. Eligible patients are newly diagnosed with stage 4 non-squamous non-small cell lung cancer with tumors that have the KEEP1 or Nrf2 mutation. Patients will be randomized to receive telglenoside or placebo in combination with pembrolizumab, carboplatin, and pemetrexed. The study will evaluate the safety and investigator-assessed PFF of telglenostat plus this standard of care chemoimmunotherapy regimen. We plan to share interim data from this trial in the second half of 2021. We are also conducting an exploratory phase 1b2 trial in collaboration with Pfizer combining telglenostat with iBrandt. In 2020, 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 CB280, a unique oral arginase inhibitor solely owned by Calthera, for the treatment of cystic fibrosis. In October 2020, we presented a trial-in-progress poster describing the trial design at the North American Cystic Fibrosis Conference. The presentation included preclinical study results which suggest CB280 significantly improved lung function and reduced pseudomonas aeruginosa colony-forming units in preclinical models. Arginase inhibition with CB280 resulted in improved central airway resistance in CFTR knockout mice and decreased lung infection in wild-type and Delta F508 CFTR-expressing mice infected with Pseudomonas aeruginosa. We plan to share data from this trial in the second half of 2021. We've also identified CB668, an investigational, first-in-class, potent, orally administered IL4I1 inhibitor as a novel immuno-oncology approach to cancer. CB668 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. IL-4I1 expression has been correlated with poor outcomes in several tumor types, has a potential role in immune invasion, and may decrease the ability of checkpoint therapy to stimulate an anti-tumor 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 CB668 was presented in November 2020 at the Society for Immunotherapy of Cancer virtual meeting. With that, I'll pass it over to Stephanie for an update on our financials.
spk10: Thank you, Keith, and good afternoon, everyone. Detailed financial results for the fourth quarter near end of 2020 were included in today's press release. I will briefly review our results on this call. Califera remains well capitalized. Our cash, cash equivalents and investments were $115.2 million on December 31st, 2020, which we believe will be sufficient to meet our current operating plan through 2022. R&D expenses were $71 million in 2020 compared to $76.3 million in 2019. The decrease was due to a 6.2 million decrease in the 1158 program and a 3.8 million decrease in early stage research, partially offset by an increase of 2.7 million in the teleglanostat program and an increase of 2.0 million in the CB280 program. R&D expenses for the fourth quarter of 2020 were 17.1 million compared to 17.9 million for the same period last year. DNA expenses were 20.4 million in 2020, compared to $16.6 million in 2019. The increase was primarily related to a $2.5 million increase in personnel related and facility costs and a $1.3 million increase in professional services. DNA expenses for the fourth quarter of 2020 were $5.6 million compared to $4.6 million for the same period last year. Interest and other income net was $1.3 million in 2020 compared with $3 million in 2019. Interest and other income net for the fourth quarter of 2020 was $0.1 million compared to $0.7 million for the fourth quarter of 2019. Net loss for the quarter in December 31, 2020 was $22.6 million. And with that, I will now return the call back over to Susan.
spk07: Thank you, Stephanie. And with that, Joelle, we're happy to open the line for questions.
spk08: Thank you.
spk09: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Mohit Banzal with Citi. Your line is now open.
spk18: Hey, good afternoon, guys. This is James on for Mohit. Thanks for the update and taking the question. First question, any color on the enrollment progress for Keepsake? I know we're on track for data later this year, but can you Give us a little bit of numbers at this point, or is that still sort of a work in progress? And then related to keepsake, there was recently some data from a KRAS inhibitor showing that STIC11 mutation patients had a higher response to the KRAS inhibitor. And I know that you guys have previously mentioned that the keepsake trial will have a good proportion of STIC11 patients. So I was wondering if Calthera has looked at combining TEL11 stat with any KRAS inhibitors.
spk13: Yeah. Hi, James. This is Keith. In terms of enrollment, so as we said, we're planning to enroll and make public some data from the initial interim analysis later this year. I think enrollment has been, I would say, impacted by COVID. I think if you probably asked anyone, there has been some impact from COVID, but it's something we're working through and we remain confident in our timeline to be able to get to data on that interim analysis later this year. So definitely some impact, but something that we are working through. In terms of the KRAS story, it's definitely one we're quite interested in, and that's sort of a, I guess I would say, a work in progress, something we're looking into on our side, but an area of a lot of interest. I mean, I think there's been a couple of different reports on the impact of STIC11 that actually between the two clinical KRAS inhibitors that were somewhat different. So that'll be interesting to see how that plays out. But that definitely remains a combination of interest.
spk02: Appreciate it, guys. Thank you so much.
spk09: Thank you. Our next question comes from Matt Pitts with William Blair. Your line is now open.
spk04: Thanks for taking my question. I guess just kind of a follow-up on that interim. I mean, this will be an interim for PFS, I assume, right, as opposed to maybe just response rates. And, Keith, are you still thinking a PFS in the control arm of around seven months, or has there been any data lately to change that assumption?
spk13: So, yeah, in terms of the assumptions, we've actually been – for this population, so for the keep one mutant population, the data that have been, you know, reported in a few different places put that probably the median somewhere in the three to five month range. And this is in front line. So these patients do very poorly. And so that's, you know, that's what we're assuming. And yeah, in terms of the data that we would be talking about, you know, it's probably a combination of PFS as well as response rates. You know, the data will be, you know, it's going to be an interim analysis, and the data will still be kind of maturing. So we're not going to be talking about fully mature data, but we do, given the short, you know, the short expected PFS, median PFS for the control arm, we would expect to, you know, hopefully see some, you know, see some daylight between the two curves and be able to see a trend in the right direction there.
spk04: Thanks, Keith. And any chance we see an update from that iBrants combo in Tinker Addict this year?
spk13: You know, we haven't gotten on that. I think it's a little hard to say exactly when. It'll likely be this year or next, but... That study really just started enrolling, so I think it's too early to say with certainty. Thank you.
spk11: Thank you.
spk09: Thank you. Our next question comes from Jonathan Chang with SVB Lyric. Your line is now open.
spk03: Hi, guys. Thanks for taking my questions. First question, can you provide your latest thoughts on how much and how mature the second half interim data set for keepsake could be.
spk13: Hey, Jonathan. In terms of the we're expecting somewhere in the range of 40 to 50 patients worth of data by the end of the year. I think that's kind of the ballpark. As we've talked about before, the analysis is not explicitly defined in the protocol and having a specific sort of statistically driven endpoint or analysis. It's not a futility analysis. It's not an early efficacy analysis. It's an administrative interim that allows us to have an early look at the data and react as appropriate, which could mean any number of things, reaching out to regulators, starting to prepare for a subsequent study. So that's the, you know, kind of the spirit of the interim. And, you know, in terms of maturity, you know, I guess I would say obviously patients who are enrolled later, you know, as we get closer to the interim analysis, those patients will be more likely to be, you know, to be censored and have less mature data. The hope is to have, you know, hopefully a couple of scans for those patients. so that we can get a feel for the median PFS. As we talked about, the median is in the range of three to five months for the control arm, we would expect. So if we can start to see separation at that early time point, that would be encouraging.
spk03: Got it. Thank you. And last question, how are you thinking about potential business development opportunities for your pipelines?
spk07: Well, this is Susan. Hi, Jonathan. In general, we remain open to partnering opportunities as one of several ways to continue to develop our pipeline. We will read out this year the first data in cystic fibrosis patients, and we have a clear picture of where we might go next. if that data look encouraging and there might be, you know, a partnering opportunity somewhere along the cystic fibrosis development timeline. And as you know, we do have an earlier stage pipeline assets that are IND ready. We have a CB73 small molecule oral inhibitor, and we also have an inhibitor for IL4I1. And, you know, Partnering is a possibility for those as well. And for Teleconstat, we'll wait and see what develops. But we're always open to partnering at the right time for the right reasons.
spk03: Got it. Thanks for taking my questions.
spk09: Thank you. Our next question comes from Arthur Heath with HC Wainwright. Your line is now open.
spk16: Hey, good afternoon, everyone. Thanks for taking my question. So I have two, so regarding the Keepsake study, maybe I missed, could you give us some color on the, regarding enrollment? And second, regarding the phase one to study of telegram in company with the in-brands, could we expect any data updated this year? Thank you.
spk13: Yeah. Hi, Arthur. In terms of enrollment for keepsake, while we don't usually give specific numbers of patients enrolled, I did mention that there has been some impact from COVID. I think it's probably multifactorial, both at the level of the sites who have staff impacted in various ways, as well as patients, since this is a frontline study, And, you know, patients getting diagnosed in the frontline setting is necessary for patients to be enrolled through the study. So, I mean, I think there are ways in which COVID is impacting clinical studies, and we're, you know, we're, you know, like everyone else, experiencing that. But, you know, as I mentioned, you know, we still remain on track, we think, for data by the end of the year. And then in terms of the IBRANTS study, that study is enrolling and we're monitoring the data there. No real update there from an enrollment perspective. I think we talked about data probably either this year or next with that study, but hard to be more specific than that at this point.
spk15: Thank you. Thank you for taking my question.
spk01: Mm-hmm. Thank you.
spk09: Thank you. Our next question comes from Matt Pipps with William Blair. Your line is now open.
spk04: Hey, coming back on. Thanks, Keith. You know, Keith, I was wondering if we could talk just to walk through some, I guess, hypothetical next steps after this interim. So, you know, obviously you'll present the data. depending on, you know, the level of activity, but is it, you know, okay, maybe we go take it to the FDA, or is it, okay, we're just going to continue to let the trial run out, or is there, does the trial have some kind of built-in adaptation to expand enrollment to maybe make it pivotal if things are looking good? Just curious, you know, what kind of potential next steps there are after this interim look?
spk13: Yeah, so that's a great question, and those are the kinds of things we're thinking about. For example, we can always reach out to FDA with the data if they're compelling and, for example, talk about breakthrough designation, talk about either amending the current study or starting the planning for a subsequent pivotal phase three. So those are the kinds of things that, by looking early, we can kind of get a start on what we think the best path path is. And again, all of those are really options and probably, you know, an interaction, you know, with FDA would be, you know, part of that if we were looking to move forward with, you know, an accelerated sort of path to approval in some way.
spk04: Do you imagine trying to reach out to the FDA would occur before you even present the data given, you know, abstract submission timelines?
spk13: I would say interacting with the FDA is independent of any kind of presentation at a meeting. I wouldn't link those to each other. Frankly, what we're talking about isn't necessarily even a ... I think what we've talked about in the past is that this may or may not be an actual conference presentation, or maybe a prelude to a conference presentation. that the discussion this year wouldn't necessarily be in the context of a conference.
spk04: Got it. Okay. Thanks, Keith.
spk13: Yep.
spk11: Thanks, Matt.
spk09: Thank you. I'm not showing any further questions. And our next question comes from Nick Abbott with Wells Fargo. Your line is now open.
spk17: Good afternoon. Thanks for taking my question. And apologies, I missed nearly all of the prepared questions. Remarks. So I'm going to ask a question on the NCI study of codeine statin to the RSO. You know, I know you may not have a lot of insight into that trial, but it was updated end of January. They're still talking about having data in June. So do you have any insight into that trial? Is this a way also to help de-risk keepsake in some of these patients who may also have a keep-on mutation?
spk13: Yes, so actually, you know, as we talk about, oftentimes, hi, Nick, by the way, we don't have any real insight at this point that we can share on the study. So, you know, I think it's an interesting question, whether it's, you know, about key mutant patients or just looking at the combination with TKIs targeting driver mutations. I think it's an interesting study. and we look forward to learning more about it. But at this point, you know, it's not something that we're, you know, we're able to, you know, to speak to.
spk17: Okay. Thanks. And then just, I know there have been a few questions on the iBrands combination. Can you remind us when the colorectal and non-small cell lung cohorts were open for the KRAF mutations, and is that the data you're referring to as possibly being available by the end of this year or beginning of next?
spk13: So that's a good question. You're testing my memory of when the study opened, and I'm not sure I'm going to be able to answer that accurately without looking it up. So I apologize. I can say the pancreatic cohort opened more recently. So that was one that we added to the study by amendment. So that was, I think, opened late last year. But the timing of the colorectal and lung cohorts opening, I don't know if I can answer that for you as we sit here. I will say, though, that the data that we could present could be those data and the pancreatic. I think data from any or all of those cohorts is possible. But we will get back to you on the timing of that at the start of the study. I'm sure I should have that ingrained in my head somewhere.
spk09: Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Jennifer McNeely for closing remarks.
spk06: Thank you, Joelle, and thanks all for joining us today. Have a great evening.
spk09: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
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