Q4 2021 Calithera Biosciences Inc Earnings Call
Okay.
Thank you for standing by and welcome to Calif, Arab Biosciences fourth quarter 2021 earnings 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 one on your telephone.
Please be advised that today's call is being recorded should you require any further assistance. Please press star zero I would now like to hand, the call over to Stephanie Wong Chief Financial Officer. Please go ahead.
Thank you operator, good afternoon, everyone welcome to our fourth quarter and full year 2021 conference call. Joining me today are Susan Molineaux, founder, President and CEO and Ml Korea Atkins Chief Medical Officer.
Earlier. This afternoon, we issued a press release, which included an overview of our fourth quarter and full year, 2020 , one financial and operational results.
Which can be accessed through our website.
Before we begin I would like to remind you that.
<unk> 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.
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 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.
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.
21 was a transformational year at Cal Sarah as we took several critical steps to transition the companys focus and core programs to developing therapies for biomarker specific patient population, while continuing to leverage the company's deep expertise in clinical development for targeted small molecule cancer therapy.
In October we announced the acquisition of two clinical stage assets from Takeda.
And a surgeon.
My vote Nib is a screen tyrosine kinase inhibitor.
Inhibitor that targets the constitutively activated b cell receptor pathway in diffuse large b cell lymphoma, and other non Hodgkin's lymphoma.
Completed phase one two clinical trials.
And it showed promising single agent responses with deep and durable activity in unselected patients with C. L. P C L.
Our initial development won't be in a b C or activated T cell you have D. C. O M. P. C are signaling and thick activation our central driver.
My vote May have shown a substantially higher response rate in a b C compared to G. B D. L. D C L.
53% O R or our overall response rate in a b C compared to a 22% O R. R. N G C P.
D L. Bcl in a retrospective analysis of completed trials Hudson's data and then the addition, recent preclinical studies have shown enhanced sick activity and sensitivity to <unk> inhibition and <unk>.
<unk>, yeah, and other non Hodgkin's lymphomas harboring mutations in Mighty 88, and door CD 79 they.
They comprise a distinct genetic subset of a b C. D. L. P. C L known to have poor outcomes with standard of care therapy.
Approximately 50% of all a b C D L b cell tumors have one or both of these new patient.
The voting is has the potential to be the first to market therapy for patients with a genetically defined subsets of <unk> yeah.
The compelling single agent overall response rate in agency deal, Yeah, and potential for further enrichment of single agent activity in genetically defined subsets of a B C. D. L. D. Yeah. It might be 88 or 79 mutations. We believe provides a well defined efficient development path too.
Potential single agent celebrating approval in these populations.
Japan is a dual and torque one two inhibitor that targets a key survival mechanism and keep one ordinary Youtube mutated tumors.
The patent searches have demonstrated promising single agent activity in patients with relapsed or refractory <unk> mutated squamous non small cell lung cancer.
It is a differentiated molecule from other M Tor inhibitors and its the only inhibitor to have strong single agent activity and nerf two mutated squamous non small cell lung cancer.
Yes.
Nerf twos mutations occur in approximately 15% are squamous non small cell lung cancer and confer a poorer prognosis for these patients.
We believe dependent or two has the potential to address a substantial underserved patient population and has the potential to be the first treatment for nerf tuned mutated squamous non small cell lung cancer.
We plan to initiate phase two studies of both the patent searches and my provoked mix in the first half of 2022 .
We also presented data from our phase one b trial of CB 288 for the treatment of cystic fibrosis at the North American Cystic fibrosis conference in November of last year.
The data shows that C V. QAD was well tolerated demonstrated linear pharmacokinetics and showed complete and continue with targeted inhibition in plasma at doses at or above 100 milligram.
<unk> also demonstrated robust pharmacodynamic effects with rapid and significant dose proportional increases in plasma arginine, a key driver of nitric oxide production enrollment.
Enrollment in the analysis of all four cohort cohort is now complete and evaluation of next steps is ongoing.
Turning to our preclinical pipeline, we have continued to advance our internally discovered preclinical pipeline of synthetic lethality target V.
V. P. S. Four a N V. P. S. Four b, our parallel gain and loss of one or the other parallel cancer cells is synthetically lethal.
V. P. S. Four program is the most advanced synthetically Saudi program, we have and we recently announced that we will be presenting a poster on the discovery of novel. He has for a small molecule inhibitors at the upcoming eight C are meeting in April .
I will pass the call over to M. O now to go into additional detail on our clinical program.
We're excited to realize the potential of microphone nip and circuits and biomarker defined population.
By focusing on well characterized genetic vulnerability with molecules that have already shown single agent activity. We believe we will be able to generate phase II data the targeted efficient study design.
To share data from these studies by the first quarter of 2023.
Okay.
Okay.
Thank you Susan I'd like to start today by providing some additional detail around our planned phase II trials, if my vote in patients with relapsed refractory <unk> with and without <unk> 88, or <unk> 79, D mutations as well as the benefits of in patients with relapsed refractory nerve to mutated squamous non small cell lung cancer.
Starting with my voting and we plan to initiate a phase III trial in relapsed or refractory non GCB D. L. D C L a dip.
Find by the Horn Gallagher them, which captures all a b C. D. L. D C L and we will enrich for Mighty 80 acre Judy said 19 mutated tumors using liquid Ngls testing patients.
Patients will be randomized to either a standard dosing schedule with 100 milligrams Q daily or an induction dosing schedule, which is 120 milligrams QD daily for 14 days, followed by 80 milligrams COO daily efficacy data from this study could position the company to initiate a registrational study, which would potentially enroll cohorts comprised of patients with.
Non GCB DLP feel and or <unk> 88, plus GBP 79 be mutated D. L. P. C. L with a primary endpoint of overall response rate such a study with target an accelerated approval pathway for my voting as a single agent in these biomarker defined subsets.
We plan to rapidly pursue combination strategies with novel <unk> standard of care therapies.
Further extend development into earlier lines of therapy in D. L. Bcl additional paths for monotherapy and combination development include Walden sniper global anemia.
Other indolent lymphomas, where my Verboten and has shown compelling single agent responses in previously completed trials now.
Now turning to span asserted we plan to initiate a phase II study of the tenants are good monotherapy in patients with nerve to mutated squamous non small cell lung cancer harboring either wild type or mutated in order to as detected by next generation sequencing. This study will strengthen the existing data onto than it started as a monotherapy in patients with squamous.
Ms non small cell lung cancer with the nerve to mutation and also evaluate its activity in north to wild type squamous non small cell lung cancer. The objectives of this phase Iia study will be dose refinement and confirmation of the selective activity in north to mutated tumors compared to wild type tumors in order to validate and implementations as the selection.
Biomarker, we believe that as phase II a is successful it would enable us to initiate phase II, b, which could be a registrational study in nerf two mutated squamous non small cell lung cancer subsequent development in squamous non small cell lung cancer could involve monotherapy and or combinations with standard of care therapies in earlier lines of treatment.
Within the biomarker defined population, including both nerf too and keep one mutant tumors.
Nurture and keep on mutations have been detected across several tumor types, providing additional indications for development of Japan asserted as monotherapy and in combination beyond squamous non small cell lung cancer, so with that summary, I'll pass it over to Stephanie for an update on our financials.
Thank you Emily and good afternoon, everyone detailed financial results were included in today's press release I will briefly review our results on this call.
Our cash and cash equivalents totaled $59 5 million at December 31, 2021, which we expect together with proceeds from our recently priced $10 million public offering will be sufficient to meet our operating plan through the second quarter of 2023.
R&D expenses for the full year 2021 was $53 4 million compared to 71 million in the prior year.
The decrease was primarily due to the telephone if that program.
R&D expenses for the fourth quarter 2021 were $13 7 million compared to $17 1 million for the same period last year.
R&D expenses related to asset acquisition for the full year of 2021 with $15 9 million due to our acquisition of SAP Hana circuit and my vote in the fourth quarter, which was comprised of a cash payment of $10 million and $40 9 million attributed to the value of the preferred stock we issue.
G&A expenses for the full year 2021 were $20 9 million compared to $20 4 million in the prior year.
G&A expenses for the fourth quarter of 2021 were $4 6 million compared to $5 6 million for the same period last year.
Net loss for the three months of nearing at December 31, 2021 was $69 2 million and $115 1 million respectively.
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.
As a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.
Our first question come from the line of Jonathan Chang of SCB Leerink. Your line is open.
Hi, guys. Thanks for taking my questions.
First question can you provide more color on the status of the planned phase two studies for my Vivant Nib and Suppan assertive what are the remaining steps to get those studies started.
Yes, so Jonathan I can answer that so the study activation is proceeding really well.
Essentially parallel tracking both the transfer of these programs from Takeda as well as the study startup process over the last several months both are progressing very smoothly.
As a complete and we've essentially the transfer process as well as regulatory reviews of both studies have been completed and we're well underway to get the sites are activated. So it's really just straight ahead shot through this site activation and patient enrollment, which is why we're still guiding to the data in <unk> 'twenty.
Great.
Got it and second question just following up on your last time on the last part of your comment.
Can you discuss reasons for confidence in the clinical execution of both of these programs such that data for both will be available by first quarter 'twenty three thank you.
Sure Yeah.
Evidence really arises from the fact that these are very very clean biomarker defined subpopulations, which are well characterized and these patients in terms of the clinician to knowledge of their genetic.
Biomarker status is well known.
Typically with regard to the squamous lung cancer and <unk> two mutant subset all these patients get tumor sequencing in.
In the frontline and so in terms of identifying patients for the relapsed refractory study, we're working with sites that have very robust.
Our robust curated local databases and G. S databases for their patients that can allow for rapid identification of both mutant and wild type patients.
And we are leveraging our prior experience running the keepsake trial and including relationships with them with the various.
G S vendors.
And in infrastructure that we developed in that study to really hit the ground running so that gives us a lot of confidence in terms of getting to that with with my vote Nib. It's a similar story a b C. D. L. P. C. L is a distinction that is known from diagnosis onwards, and so in terms of finding these patients it's well known from their clinics.
History, whether they fit the non GCB slashed ADC label and the fact that we're using liquid mgs again to enrich for Mighty 88 C. D say 90 mutant patients again from a timing and efficiency standpoint allows for rapid identification of those patients as well, we're working with very well experienced sites in terms of.
Lymphoma physicians, who have either already to use the drug in previous studies in very large centers, where they know we have high volumes of patients that are also characterized genetically.
Local level. So the selection of sites in both studies with the streamlined in order to make sure that we have the high yield of patients from every site that we take.
Yeah.
Got it thanks for taking my questions.
Sure.
Thank you. Our next question comes from Roger song of Jefferies. Your question. Please.
Great. Thank you maybe just quickly follow up on this.
Q phase two trials.
In the initial data in one Q, what should we expect kind of how much data. We can assume from that initial readouts also what kind of what they that the phase two data ultimate today will trigger you to move forward.
The Registrational trial as you mentioned.
Right. So the you know the the benefit we have here is that both of these molecules already have preexisting data is showing that they are both clearly active as a single agent.
And we know the numbers with regard to response rates in those prior studies that.
That gave us the confidence to get them in the first place I mean in terms of the fact that this is an overall response endpoint study that's open label and we'll be seeing the data in real time and give us a lot of flexibility in terms of.
The types of data that we will see so I think in terms of the fact that this is.
Rapid time to responses for both molecules.
Typically in my vote that responses tend to happen very quickly within the first one to two cycles and the same thing is actually seeing for dependent search had been previous studies. So the time from a patient enrolling two meaningful efficacy data for each patient is pretty short and so with that being said and given the the numerator in terms of or ours.
Already fairly high, especially for the lymphoma.
In the <unk> setting give us a lot of.
Confidence that we could have a meaningful dataset by the first quarter of 'twenty three.
Got it okay.
Maybe just quickly touch on the C. D E B to $2 80. So you have finished a small pool hall and doing the data analysis would you announce that data this year and what could be the path forward as you as you evaluate the next steps for this combo.
Right, so with that molecule again, the dose escalation was completed in terms of the data from the final cohort analyses at the trends that we saw and reported on in the first three dose levels with regard to.
Pharmacodynamic effects arginine increases as well as trends in F E and F N B, one where essentially maintained and that that.
Final dose level. So again, the overall trends continue to stay consistent and definitely we there is the option to present that data at a later time point.
We're continuing discussions with our advisors in the cystic fibrosis foundation as well as the therapeutic development network in terms of how these data could best inform.
The design of a potential phase II dose finding type study and those discussions are ongoing right now.
Okay.
Got it. Thank you. Thank you for taking my question.
Thanks Raj. Thank you again to ask a question. Please press star one on your Touchstone telephone again Thats Star one on your touched on telephone to ask a question. Our next question comes from Arthur He of H C. Wainwright. Please go ahead.
Hey, good afternoon, everyone.
Australian four okay. So I just wanted to follow up on those two phase two studies you guys going to initiate it.
Could you repeat the optimization of dosing regimens for it.
Another about nib and I wonder.
Is this similar dose optimization strategy go to apply to the <unk> said.
For the study.
Yeah. So great question. So yes, both studies do have an element of dose refinement included for my vote Nib are again, the fact that both of these molecules have that extensive dose schedule work done previously with Takeda is studies gave us a really good starting point and this is really more of those fine tuning.
Especially because we were going in a biomarker defined population. So for my voting at the two dose levels 100 milligrams. Two day is the previously established recommended phase two dose from prior dose escalation expansion trial, we see an opportunity to explore a further dosing strategy specifically in induction dosing strategy and that's really taking.
Advantage of the molecules PK properties, namely that it had.
You know pretty long half life. It has a very high volume of distribution and considering that.
We based on our analysis of this molecule. It it has a tendency to accumulate in tissue and specifically tumor and large concentrations that gives you an opportunity to evaluate a strategy, where you get a large bolus of drug in quickly. These aggressive tumors to get rapid disease control and once you get to a <unk>.
Response basketball off too, it's still active but more tolerable long term dosing strategy to maintain that response. This is not unusual in the context of lymphoma.
Lymphoma, specifically other approved drugs use a very similar approach. So we wanted to explore that.
The advantage of the fact that the molecules properties already make it amenable to evaluating that for some time the search or it's a similar sort of fine tuning that we're doing the three milligram QD dose is.
A dose that was previously studied and actually showed the efficacy signal in nerf two mutant screen patients.
Again based on the molecule PK properties, namely a shorter half life with.
Tox profile, where we know that more of the Gi toxicities are ever more see mats related.
And that you might be able to get to a or.
Higher accumulative exposure by using a lower dose schedule, namely to B I D could get you improved efficacy with the maintaining the very good tolerability profile that we already see a three milligram daily dose. So those are the rash.
The rationale for why we're doing what we're doing with regard to dose refinement, but again, we think that it's because it's a fine tuning of not repeating for example, a full dose escalation. It can happen very quickly and in parallel with getting the efficacy data.
Thank you. Thank you that's really helpful and so.
As for your new Vps for April inhibitor program could.
Could you give us more color on regarding the prevalence of the V. P. S. Four.
<unk> deletion.
Different cancer type and.
Also how soon could we expect these program advancing to the clinic. Thank you.
I could I could give you the prevalence so in the homozygous deletion of EPS for B occurs in 1% to 3% of all solid tumors or with heterozygous deletion is much more prevalent in the IRA incidents approximately two thirds of specifically colorectal cancer and pancreatic cancer.
I guess deletions and there's evidence to show that the dependents the increased dependence on V. P. S foray.
Is still high in the heterozygous deletions of EPS for be giving you.
A substantial opportunity to evaluate a very large.
Set of tumors and a large subset of colorectal and pancreatic.
I'm going to let Susan answer your second part of your question.
[laughter] well, we're presenting them.
Early data at ACR next week, and we do have our vps for inhibitors and we're moving those molecules forward. So we're in lead optimization and we.
We hope to continue to advance this program and can give you future guidance on when we might be in the clinic.
Awesome. Thank you. Thank you for taking my question.
Sure.
Thank you at this time I'd like to turn the call over to Susan Molineaux for closing remarks ma'am.
Thank you and thanks to all for joining us today and have a good evening.
This concludes today's conference call. Thank you for participating you may now disconnect.
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