Ladies and gentlemen, thank you for standing by and welcome to Calithera Biosciences 1Q 2022 Earnings. At this time, all participants are in a listen-only mode. Later we'll conduct a question-and-answer session and instructions will follow at that time. . I would like to turn the conference over to your host Ms. Stephanie Wong. Please go ahead..

Thank you, Grace. Good afternoon, everyone. Welcome to our first quarter 2022 conference call. Joining me today are Susan Molineaux, Founder, President and CEO; and Emil Kuriakose, Chief Medical Officer.

Earlier this afternoon we issued a press release, which included an overview of our first quarter 2022 financial and operational results, which can be accessed through our website at calithera.com.

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

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

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

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

Thanks Stephanie. Good afternoon, everyone, and thank you for joining us for today's conference call. Calithera is off to an exciting start in 2022 as we continue to advance our pipeline of investigational small molecule oncology compounds to address the needs of biomarker-defined patient populations.

We also strengthened our balance sheet with the close of our underwritten public offering of $10 million in gross proceeds in April of this year, resulting in $8.5 million of net proceeds after deducting underwriting discounts, commissions and offering costs.

Focusing on our clinical pipeline, we have made significant progress in completing the transfer of Mivavotinib and Sapanisertib materials from Millennium Pharmaceuticals a subsidiary of Takeda Pharmaceutical Company to Calithera and are well into site start-up activities for Phase 2 monotherapy trials for each compound.

We remain on track to begin enrollments in these trials in the second quarter of this year and expect to share data by the first quarter of 2023.

We believe that by focusing on well-characterized genetic vulnerabilities with molecules that have already shown single agent activity, we will be able to generate Phase 2 data with targeted efficient study designs and device potential paths for rapid approval in genetically defined patient populations.

Turning to our preclinical pipeline, we have continued to advance our internally discovered preclinical pipeline of synthetic lethality targets, most notably VPS4A and VPS4B, which are paralog gene for a loss of one or the other paralog intensive cells is synthetically lethal.

In April, we presented data describing VPS4A inhibitors at the American Association for Cancer Research or AACR 2022 Annual Meeting. The presented poster details are discovery of what we believe to be are the first active on target VPS4A inhibitors. Emil will describe our findings in further detail.

We are continuing to advance multiple inhibitors in series through lead optimization and look forward to updating you on our progress as they advance toward first in human clinical studies.

In February of this year, we also received good news from our partner Antengene Investment, who announced the approval of a first in human study of ATG-037 formerly CB-708 in patients with locally advanced for metastatic solid tumors, ATG-037 was discovered by Calithera and in May of 2021, we entered into a license agreement with Antengene where we granted them an exclusive worldwide license to develop and commercialize ATG-037, which is a CD73 inhibitor.

Under this agreement, Calithera received an upfront payment of $3 million and may receive potential development, regulatory and sales milestones of up to $250 million. I would like to announce also that we have decided not to pursue further development of CB-280 in CF cystic fibrosis at this time.

We will dedicate our resources towards our oncology programs. While CB-280 showed encouraging safety and biomarker data in the completed Phase 1 study in CF patients, we came to this conclusion after reviewing our data and in addition, evaluating the impact of recent significant changes in the CF therapeutic and regulatory landscape.

And now I will pass the call over to Emil to go into additional details on our program..

Great, thank you, Susan. I'd like to start today by providing some additional detail around the data presented at ACR 2022 on our novel VPS4A inhibitors. The poster detailed Calithera's discovery of VPS4A inhibitors.

These data validate the synthetic lethal interaction between the gene paralogs called Vacuolar protein sorting-associated protein 4-A or VPS4A and VPS4B. We believe that these data provides a first preclinical evidence supporting a newly discovered series of compounds designed to target these proteins for cancer treatment.

We mind CRISPR genetic the loss of function data and associated molecular data sets from the broad Institute of MIT and Harvard's Cancer Dependency Map project datasets to identify pairs of gene paralog, which were then prioritized for potential drug targets.

This work resulted in the identification of VPS4A and VPS4B as promising targets, simultaneously knocking down VPS4A and VPS4B consistently resulted in cell death.

We then conducted multiple studies to validate the paralog gene pair demonstrating that cells with VPS4B homozygous or heterozygous loss are sensitive to VPS4A knockdown while cells without VPS4B are not.

Utilizing that VPS4A and VPS4B paralog genes as targets, we identified a novel series of small molecule inhibitors, among the finding shared at the AACR Congress, our data detailing the performance of one inhibitor of VPS4A and VPS4B ATPases activity.

Turning to our clinical pipeline; we're currently activating sites for the Phase 2 trials of mivavotinib in patients with relapse refractory, non-GCB, also commonly referred to as ABC DLBCL with and without MYD88 or CD79 mutations as well as pan AER in patients with relapsed/refractory NRF2 also known as NFE2L2 mutated squamous non-small cell lung cancer.

Both trials are on track to begin enrollment in the second quarter of this year. The Phase 2 trial of sapanisertib planned as a two part study is a monotherapy study in patients with relapse refractory NRF2 mutated or wild type squamous non-small cell lung cancer as detected by Next Generation Sequencing.

The objectives of Phase 2A are dose refinement and confirmation of the selective activity in NRF2 mutated tumor as compared to wild-type tumors to validate NRF2 mutation as a selection biomarker.

The Phase 2A data intended to substantiate the single agent activity that was already seen with the sapanisertib in patients with relapse refractory NRF2 mutated squamous lung cancer, and also evaluate its activity in NRF2 wild-type squamous lung cancer.

We believe that if we successfully achieve the objectives of Phase 2A, we will be able to initiate Phase 2B which in the relapse -- in the same refractory NRF2 mutated squamous lung cancer population, which could be registrational.

The specific design of Phase 2B will be informed by data from Phase 2A and maybe a single arm expansion cord evaluating sapanisertib in relapse refractory NRF2 mutated squamous lung cancer patients at the selected dose and/or a randomized study comparing the selected dose of sapanisertib to standard of care established therapy.

Subsequent development in squamous lung cancer could involve monotherapy and/or a combinations with standard of care therapies in earlier lines of treatment within these biomarker defined subpopulations of NRF2 and KEAP1 mutant tumors.

NRF2 and KEAP1 mutations have been detected across several tumor types at combined frequencies of up to 27% providing additional indications for development of sapanisertib as a monotherapy or in combinations in tumors beyond squamous non-small cell lung cancer.

Now turning to mivavotinib, we're initiating a two-part Phase 2 trial in patients with relapse or refractory non-GCB or ABC DLBCL as defined by the standard Hans algorithm with enrichment for MyD88 and CD79b mutations using ctDNA-based liquid NGS.

The Phase 2A part of the trial will confirm activity in the biomarker-defined subsets and further refined dose and schedule. This trial is also on track to enrol first patient in the second quarter and we expect to share data by Q1 2023.

Data from this study will inform Phase 2B, which would potentially enrol expansion cohorts comprised of patients with relapse refractory non-GCB, DLBCL MyD88 and CD79b mutant DLBCL or both with a primary endpoint of overall response rate.

Such a study could enable an accelerated approval pathway for mivavotinib as a single agent in these biomarker defined subsets. Mivavotinib has a potential to be the first treatment specifically for non-GCB DLBCL, a population of patients with a historically poor prognosis and unmet clinical need.

It also has a potential to be the first treatment for a genetically defined subset of DLBCL, mainly patients with MyD88 or CD79b mutations. We plan to pursue combination strategies with novel and/or standard of care therapies to further expand development in earlier lines of therapy in DLBCL.

Additional tasks for monotherapy and combination development include other non-Hodgkin lymphomas like Waldenstrom's macroglobulinemia, where the majority of tumors are known to have MyD88 mutations or other indolent lymphomas where mivavotinib has already shown compelling single agent responses in previously completed trials.

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

Thank you, Emil. Detailed financial results were included in today's press release. I will briefly review our results on this call.

Our cash and cash equivalent totals $44.7 million at March 31, 2022, which we expect together with proceeds from our recently completed public offering will be sufficient to meet our offering plan through the second quarter of 2023. R&D expenses for the first quarter 2022 were $9.6 million compared to $15.3 million in the same period last year.

The decrease of $5.8 million was primarily due to a decrease in the telaglenastat program, partially offset by increases in the sapanisertib and mivavotinib programs. G&A expenses for the first quarter of 2022 were $4.3 million compared to $45.4 million in the same period last year.

The decrease of $1.2 million was primarily due to decreases in personnel related costs. Net loss for the three months ended March 31, 2022 was $13.8 million. And with that, I will now return the call back over to Susan..

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

And your first question comes from the line of Jonathan Chang from SVB Securities. Your line is open..

Hi guys. Thanks for taking my questions. First question, it looks like there'll be Phase 1B combination data at ASCO from a study that was initiated before you guys in license for the drug.

My question is, can you guys help set expectations ahead of those data? How much new data will be available versus previous disclosures?.

Oh, I can answer that. So, essentially this was a study that was initiated well before we took the program in. So I wouldn't be able to provide guidance on that question again, because it wasn't a study that we had initiated..

Got it. And second question.

What are the remaining steps to initiating the mivavotinib and sapanisertib Phase 2 studies?.

Like we said, the studies are already essentially being initiated. We're actively opening sites at the moment. And so again, we're expecting enrollment of the first patient in the first half of this year and still guiding to data in Q1 '23..

Got it.

And, just last question for me, can you provide more color on the CD73 inhibitor partnership with Antengene? And specifically, can you elaborate on any potential near-term milestones you could receive?.

Hi Doug. So it's Stephanie. As you know, we received the upfront of $3 million and there're $252 million in future milestones. We haven't provided any more guidance beyond that. But we are pretty excited that, that study is about to be underway..

Got it. Thanks for taking my questions..

Thank you. And your next question comes from the line of Nick Abbott from Wells Fargo. Your line is open.

Good afternoon. Thanks for taking our questions. First one is in the prepared remarks, and I apologize, I missed the first part of the call, but in the prepared press release, at least CB-280 is not discussed.

Is there an update on that program?.

Yes, Nick, I can answer that. So basically, as you know, we showed data from the Phase 1B trial sort of interim data from that escalation where the drug showed excellence safety, as well as encouraging trends both in terms of PKPD as well as biomarkers.

So, in fact, the molecule did what it was supposed to do for the purpose of that study, which was safety, PKPD and biomarkers and the reason that we decided not to pursue go right into the next state of development, which would be Phase 2 in SDS population was really the dramatic shifts in the treatment landscape and really the regulatory landscape.

What I mean by that is with the approval of the highly effective modulators, namely Trikafta, it's really shifted the unmet need population within the disease.

And so it's a matter of active debate both within the academic community as well as amongst the regulators in terms of what is the population now in CF that is it the standard historic clinical trial population that one should test the new drug in and what are the bars for efficacy with regard to FEV1 and other endpoints? And I think this is a problem that's -- it's not really a problem.

It's good for patients, but it's actually being discussed actively within the CF communities. So we thought that it was premature to go into that Phase 2 study without answers to these questions in the field already determined. And plus we want to dedicate our resources to the new oncology program. So it was really a portfolio prioritization..

Okay. Very comprehensive. So is another opportunity to partner that with a company who has sort of more expertise or focus on CF..

Yeah. At this point we're not developing the molecule going at this time, as we said, but like we said, if there is potential for that, I think we'd be open, but I'll hand it up to Susan, if she wants to add anything more..

I would say the same thing. We'll monitor the CF landscape and if there are opportunities for partnership, we'll certainly pursue them and we can revisit at a later date, but for now, we're not planning on taking CB-280 directly forward in a trial..

Okay. Thank you.

And then on the VPS4 inhibitors, so we saw the data at AACR, what do you think the timeline is to an IMD filing for that program?.

So, yeah, we're currently in lead optimization for that, and we hope to advance this program. We can give you future guidance on when we might be in the clinic. But we can't guide to that at this moment..

Okay. Fair enough. Thanks a lot..

Thank you. And your next question comes from the line of Swayampakula Ramakanth from H.C. Wainwright? Your line is open..

Thank you. Some of the questions that I had have been answered, but in general Susan and Stephanie I'm just trying to understand how you are trying to optimize your resources with two pretty much clinical programs that pretty much have started and another program, which probably can get started maybe a year, year and a half from now.

How do you see your resources being used through -- getting through this three pipeline products? In the sense, is there going to be some sort of staggering, between the three programs or you can run these three to the extent that and you would have data in the next year or so. So if you need to go back to the market, then you will have the chance..

Hi, okay. It's, Stephanie. So our current cash runway is due first half of 2023, and we anticipate having data from the two clinical assets in the first quarter. So I think we have sufficient cash resources to optimize that as well as put some efforts into the synthetic program..

Okay, perfect. Thank you..

Thank you. And your last question comes from the line of Aydin Huseynov from Ladenburg. Your line is open..

Hi thank you for taking my questions. I have one regarding the timeline. So could you clarify, how long would it take you to enrol patients in each of the mivavotinib and sapanisertib trials? And so I see that you guide now first quarter '23 before it was four quarter '22 first quarter '23.

So do you expect that guidance to change as we move forward into this year?.

No, we're still guiding to 1Q '23 for data. And, like we've said earlier, these are open label response rate endpoint studies in two drugs that we already know from earlier trials show very quick responses. And the signal is pretty binary in terms of their efficacy.

So, we do expect to be able to still generate data in Q1 '23 with the pace of site activations that we're currently seeing with the studies together. We're still confidently guiding to that timeline..

And could you clarify how many patients in each of the trials you are planning to enrol and given the earlier responses, where do you see -- where do you expect to see earlier responses in which of the trials?.

Yeah, and the Phase 2A part of these studies, as I said, in the prepared remarks is essentially substantiating previously observed efficacy.

So from the standpoint of seeing a positive signal of efficacy, we don't think we need that many patients to be able to determine whether or not we're seeing confirmatory activity that was already previously seen in other studies.

And, we're working with sites that have high volumes of patients who frequently do NGS on all their patients, so that patient identification is made very easy. And so to that point again, we think we'll have a meaningful data set that guides us to the next part, which is Phase 2B for both studies within that timeframe..

Got it. Got it.

And the last one, given where this focus trade is right now, would you consider outlicensing one of the programs and focus on another? I know you probably don't have preference one over another, but would you even consider kind of focusing just in one asset, one indication as opposed to developing two assets at the same time?.

We think both drugs have really good value, which is exactly why we got both of them. And we think both of them have really strong potential to be successful and be real drugs in these biomarker defined groups. So no, I don't think we would prioritize one over the other at this point..

Got it. Got it. Thank you. Appreciate that..

Thank you. And I'm showing no further question at this time. I would like to turn conference back to our President and CEO Ms. Susan Molineaux for any closing remarks..

Thank you, Grace. And thanks all for joining us today. Have a good evening..

Thank you, ladies and gentlemen. This concludes today's conference call. Thank all for joining..